Factors affecting clinical outcomes of continuous and intermittent plasmapheresis in patients with severe hypertriglyceridemia.

INTRODUCTION: Acute hypertriglyceridemia is considered a category III indication for plasmapheresis. The use of plasma as replacement fluid (RF) has been suggested to replace the consumed lipoprotein lipase. Heparin when used as an anticoagulant could possibly release lipoprotein lipase, thereby increasing triglyceride clearance. METHODS: The impact of RF (albumin vs fresh frozen plasma (FFP) and anticoagulant (ACD-A vs. heparin) on triglycerides following plasmapheresis in 27 patients with severe hypertriglyceridemia (SHTG) was investigated. A paired study of four patients with recurrent SHTG was conducted, evaluating continuous (Optia) versus intermittent flow plasmapheresis (Haemonetics). RESULTS: Shorter procedures positively impacted triglycerides (TG) drop post-sessions p < 0.05. In albumin sessions, patients who used heparin demonstrated significantly greater drop in TG and required less sessions than did those with citrate p < 0.05. In heparin sessions, patients who used albumin demonstrated significantly greater drop in triglycerides and required less sessions than did those with FFP p < 0.05. Three of six patients who used FFP and heparin showed a triglyceride drop of 11.7% following three sessions and a 50% drop with one albumin session. Compared with Haemonetics, Optia removed comparable volumes of plasma in less time, processing smaller blood volumes and using less citrate p < 0.05. Patients demonstrated significantly lower drop in TG and required more sessions with Haemonetics than they did with Optia p < 0.05. CONCLUSION: Shorter procedure was the main predictor for effective TG clearance. This can be achieved by continuous apheresis technology, particularly when using albumin as RF. TG removal via Optia seems to be optimized by using heparin.

Hyperchloremic metabolic acidosis after plasma exchange in a patient with renal transplant rejection: A case report.

Therapeutic plasma exchange (TPE) is an effective treatment for several renal disorders, including renal transplant rejection. However, repeated plasma exchanges can result in various metabolic disturbances and complications. We present a 61-year old male with a medical history of type 2 diabetes, hypertension, successfully treated multiple myeloma, and a post-mortem kidney transplantation 7 months prior to presentation. The patient was hospitalized with an antibody-mediated transplant rejection for which treatment with methylprednisolone, TPE with a 40 g/L albumin solution as a replacement fluid, and intravenous immunoglobulins was initiated. After four TPE treatments, the patient developed gastrointestinal complaints and muscle weakness. Despite daily oral bicarbonate supplementation, laboratory tests revealed a hyperchloremic metabolic acidosis: bicarbonate 11.7 mmol/L, chloride 111 mmol/L, and sodium 138 mmol/L. Metabolic acidosis due to citrate accumulation was ruled out with a normal total-to-ionized calcium ratio. After treatment with intravenous bicarbonate supplementation, the symptoms disappeared. Analysis of the albumin solution showed a chloride concentration of 132 mmol/L. This is the first case that describes severe metabolic acidosis after multiple sessions of TPE with an albumin solution in a patient with impaired renal function. The hyperchloremic metabolic acidosis is the result of administration of large volumes of an albumin solution with high chloride concentrations. Special attention should be paid to the acid-base balance during TPE in patients with impaired renal function. Future research should investigate the incidence of hyperchloremic metabolic acidosis during TPE in patients with impaired renal function.

Customized Citrate Anticoagulation versus No Anticoagulant in Continuous Venovenous Hemofiltration in Critically Ill Patients with Acute Kidney Injury: A Prospective Randomized Controlled Trial.

INTRODUCTION: The use of anticoagulants during continuous renal replacement therapy (CRRT) is essential. Regional citrate anticoagulation (RCA) is recommended rather than systemic heparinization to prolong the filter's lifespan in patients at high risk of bleeding. However, commercial citrate is expensive and may not be available in resource-limited areas. The objective of this study is comparing filter life between our locally made customized RCA and no anticoagulation. The primary outcomes were the first circuit life in hours and the number of filters used within the first 72 h of therapy. METHODS: We conducted a single-center prospective randomized controlled trial in critically ill patients requiring CRRT. The participants were randomized to receive continuous venovenous hemofiltration (CVVH) with either customized RCA or no anticoagulant. RESULTS: Of 76 patients, 38 were randomized to receive customized RCA and 38 to receive CVVH without anticoagulant. There was no significant difference in baseline characteristics between the two groups. Compared to anticoagulant-free group, the median circuit life of customized RCA group was significantly longer [44.9 (20.0, 72.0) vs. 14.3 (7.0, 22.0) hours; p < 0.001]. The number of filters used within 72 h was significant lower [2.0 (1.0, 2.0) vs. 2.5 (1.0, 3.0); p < 0.015]. RCA was prematurely discontinued in 5 patients due to citrate accumulation (2 cases) and severe metabolic acidosis requiring higher dose of CVVH (3 cases). No differences in bleeding complications were observed (p = 0.99). CONCLUSION: Customized citrate-based replacement solution improved filter survival in CVVH compared to anticoagulant-free strategy. This regimen is safe, feasible, and suitable for low- to middle-income countries.

Therapeutic Plasma Exchange: Core Curriculum 2023.

From producing individual blood components for transfusion to the removal of pathogenic substances, apheresis is a cornerstone of modern medical therapies. The use of therapeutic plasma exchange (TPE), in which plasma and its soluble constituents are removed from the body in exchange for a replacement fluid, can be organ- and life-saving in many diseases. Given the notable similarities between TPE and hemodialysis, the nephrologist is often responsible for managing TPE. As such, one must be familiar with the technologies, approach to therapy, indications for use, and complications. TPE uses centrifugation or membrane separation technologies, with the latter able to be performed with certain hemodialysis machines familiar to the nephrologist. Furthermore, primary kidney diseases such as anti-glomerular basement membrane disease are frequently associated with autoantibodies, potentially making them ideal candidates for TPE. Nevertheless, the use of TPE in many kidney diseases is controversial because of the lack of supporting evidence. This review discusses TPE from the perspective of a nephrologist responsible for prescribing and managing TPE, as well as nephrologists engaged in the care of patients undergoing the procedure.

Two cases of brand-specific albumin sensitivity in patients receiving regular therapeutic plasma exchange.

Therapeutic plasma exchange (PLEX) involves the removal of detrimental substances, commonly pathogenic antibodies or toxins, from a patient's blood by exchanging their plasma with a replacement fluid. While a variety of replacement fluids are available, human albumin (4-5 %) is the most commonly used, as it is widely available, easily stored, and generally well tolerated. Despite its excellent safety profile, adverse reactions to albumin are well documented, ranging in severity from mild allergic symptoms to severe anaphylaxis. This report describes two cases of patients receiving frequent PLEX who developed sensitivities to human albumin. These patients differed substantially in the manifestations of their symptoms, the duration of their treatment, and their medical indication for PLEX. In both cases, symptom onset occurred shortly after completion of plasma exchange procedures and lasted for several hours. Symptoms disappeared when the patients were switched to albumin from a different manufacturer, suggesting that the reaction was specific to that formulation of albumin and not to the albumin itself. These cases highlight the possibility of manufacturer-specific acquired albumin sensitivities and provide a simple framework for the initial approach to the management of such reactions.

Sodium-Based Osmotherapy in Continuous Renal Replacement Therapy: a Mathematical Approach.

Cerebral edema, in a variety of circumstances, may be accompanied by states of hyponatremia. The threat of brain injury from hypotonic stress-induced astrocyte demyelination is more common when vulnerable patients with hyponatremia who have end stage liver disease, traumatic brain injury, heart failure, or other conditions undergo overly rapid correction of hyponatremia. These scenarios, in the context of declining urinary output from CKD and/or AKI, may require controlled elevations of plasma tonicity vis-à-vis increases of the plasma sodium concentration. We offer a strategic solution to this problem via sodium-based osmotherapy applied through a conventional continuous RRT modality: predilution continuous venovenous hemofiltration.

A brief review of common mathematical calculations in therapeutic apheresis.

Apheresis is defined as the removal of blood from the body, its separation into constituent components, and removal or manipulation of one of these components prior to intravascular return with or without the addition of replacement fluid. Patients undergoing therapeutic apheresis often have multiple comorbidities, potentially affecting their hemodynamic status. Thus, a thorough understanding of apheresis principles and calculations is required for the performance of safe, efficacious, and successful procedures. The performance of simple transfusions or red blood cell exchange procedures is additionally complicated by the difficulties inherent in the procurement of compatible blood products, and the emphasis on minimizing exposure to unnecessary blood products. It is essential that apheresis physicians be able to accurately evaluate the risks/benefits inherent in the procedural options and efficiently stratify patients to the optimal therapeutic modality. The formulas requisite for performing therapeutic apheresis calculations are herein reviewed.

Risk of hypotensive reactions is increased when using partial saline replacement for therapeutic plasma exchange.

BACKGROUND: Partial normal saline replacement during plasma exchange procedures is a common practice to reduce procedure costs but may increase the risk of adverse events, such as hypotension and citrate reactions. The goal of this study was to compare adverse event rates for the patients that used albumin or albumin/saline as replacement. STUDY DESIGN AND METHODS: A retrospective chart review was done of plasma exchange procedures that used all albumin or 80% albumin to 20% normal saline (80/20) as replacement. The procedure type (all albumin vs 80/20), the percent of normal saline used, age, gender, and adverse events during the procedure were recorded. RESULTS: During the study period, 3624 procedures were documented for 401 patients (46% female), age range 0 to 93 years, of which 2453 (67.7%) used 80/20. Overall 91 procedures (2.5%) resulted in a hypotensive event, 26 (0.7%) of which were classified as moderate to severe hypotension, and 40 (1.1%) had reported citrate toxicity. After adjusting for age, gender, and diagnosis using a generalized linear mixed model and backward model selection, results showed that 100% albumin had a significantly lower risk of having hypotension than 80/20 (odds ratio (OR): 0.531 [0.298, 0.946], P = 0.032) and moderate to severe hypotension (odds ratio: 0.140 [95% confidence interval (CI): 0.031, 0.628], P = 0.010). Older age was also predictive of having hypotensive reactions (OR[95%CI] = 1.017,[1.0, 1.034], P = 0.047). CONCLUSION: Partial saline use as a replacement fluid with albumin during plasma exchange is associated with an increased risk of hypotension. Use of saline as replacement fluid during plasma exchange should be minimized especially in older patients.

Effects of preoperative plasma exchange therapy with albumin replacement fluid on blood coagulation in patients undergoing ABO-incompatible living-donor kidney transplantation using rotational thromboelastometry.

BACKGROUND: ABO-incompatible living-donor kidney transplantation (LDKT) requires immunotherapy and plasma exchange therapy (PEX). PEX with albumin replacement fluid reportedly decreases fibrinogen levels. However, no reports have described the effects of PEX with albumin replacement fluid on blood coagulation parameters and blood loss during the perioperative period. Therefore, we investigated the effects of preoperative PEX on blood coagulation parameters and blood loss during the perioperative period in patients undergoing ABO-incompatible LDKT as measured by rotational thromboelastometry (ROTEM®). METHODS: Twenty-eight patients undergoing LDKT were divided into the PEX group (ABO incompatible with PEX, n = 13) and non-PEX group (ABO compatible without PEX, n = 15). ROTEM® parameters, standard laboratory test parameters, bleeding volume, and transfusion volume were compared between PEX and non-PEX group. MCEplatelet, which represents platelet contribution to clot strength and where "MCE" stands for maximum clot elasticity, was calculated from the difference in MCE between EXTEM and FIBTEM. RESULTS: The bleeding volume during surgery and the intensive care unit (ICU) stay was significantly higher in the PEX than non-PEX group (p < 0.01). Maximum clot firmness (MCF) of EXTEM (MCFEXTEM), MCFFIBTEM, and MCEplatelet was significantly lower in the PEX than non-PEX group (p < 0.01). In the PEX group, the bleeding volume during surgery was very strongly correlated with the baseline MCFEXTEM and MCEplatelet, and the bleeding volume during the ICU stay was strongly correlated with the postoperative MCFEXTEM and MCEplatelet. CONCLUSIONS: These results suggest that the increased blood loss in the PEX group during surgery and the ICU stay was associated with decreased platelet contribution to clot strength as measured by ROTEM®. TRIAL REGISTRATION: UMIN-Clinical Trial Registry UMIN000018355 . Registered 21 July 2015.

Successful Practice Transitioning Between Hemodialysis and Hemodiafiltration in Outpatient Units: Ten Key Issues for Physicians to Remember.

Hemodiafiltration (HDF) during chronic renal replacement therapy (RRT) is a relatively new practice phenomenon, emerging over the last two decades. While the technological platforms utilized during chronic RRT are in many cases similar or effectively identical to conventional hemodialysis (HD), significant differences may emerge in daily practice. Several authors of this review moved practice site between the United States and the European Union and transitioned from an HD-based practice to predominantly HDF-practicing networks. In doing so, we became keenly aware of the potential pitfalls nephrologists may be facing during such transitions. This brief review is intended to provide a succinct overview of several practical concerns and complications nephrologists may encounter in daily practice of end-stage renal disease care, including but not limited to management of electrolytes, renal anemia and treatment goals and settings during HDF.

A mathematic analysis of different manners of replacement fluid infusion in continuous veno-venous hemofiltration / 中华危重病急救医学

ObjectiveTo establish a mathematical formula for choosing the manner of replacement fluid infusion in continuous renal replacement therapy (CRRT), so as to provide the basis for improving the treatment effect. Methods A mathematical formula for choosing the manner of replacement fluid infusion with continuous veno-venous hemofiltration (CVVH) was taken as an example, and it was compared with the result of standard replacement fluid in order to analyze the effect of different manners of infusion.① Comparison parameters: the plasma volume (Vreturn) and some electrolyte concentration (Creturn) in back way of CRRT (if other thing was solute, filter coefficient should be 1.0).② Research objects: the actual replacement fluid (for example, the most complex should be sorted into A and B type) mode (pre or post) was compared with the standard replacement fluid (the A and B in one).③ Based on the formula of standard replacement, four equations in different conditions were derived: pre-dilution and post-dilution mode; same direction and same ratio; same direction and different ratio; different direction and same ratio; different direction and different ratio.Results The calculated results of Vreturn (except hematocrit) and Creturn were same to the standard only following the rule of same direction and ratio for A and B no matter pre-dilution mode or post-dilution mode, and it was different from the standard in others. In pre-dilution mode and post-dilution mode, it showed:① A and B in same direction and different ratio: Vreturn and Creturn were different from the standard for the alterative ratio of B.② A and B in different direction and same ratio: Vreturn was same to the standard, but Creturn was different from the standard for the completely different and more complex computational formula.③ A and B in different direction and different ratio: both Vreturn and Creturn were different from the standard. The different Vreturn was due to the different ratio of B. The different Creturn was caused by different ratio of B and the completely different computational formula.Conclusions① For parts of replacement fluid which must be separated ( for example, bicarbonate formula ), the result is same to the standard, and is predicted and mastered only following the rule of same direction and ratio. Otherwise, we need to calculate the two parameters over and over again. The result will run out of our judgment. The wrongness of losing water and electrolyte disorders maybe come out.② Accordingly,the formula could be used to analyze the same case like the separated replacement infusion, for example, a large number of citrates as regional anticoagulation were infused only in the front of filter, while the replacement fluid can be done in varied forms.

Comparison of the effects of virus inactivation of plasma and albumin in plasma exchange liquid gallinger therapy on the treatment of severe systemic lupus erythematosus / 中国基层医药

Objective To compare the clinical curative effect of virus inactivating activity of plasma and albumin compound sodium chloride injection in liquid plasma exchange(PE)for treatment of severe systemic lupus erythematosus(SLE).Methods A total of 75 cases of severe SLE patients were randomized according to the number table method patients for virus inactivation of plasma group A(37 cases)and liquid albumin plasma group B (38 cases). The changes of immunoglobulin protein(IgG,IgA,IgM),ESR,complement C3,C -reactive protein(CRP),blood urea nitrogen(BUN)and serum creatinine(CR)index in the two groups were observed before and after PE.Clinical SLE-DAI(systemic lupus erythematosus disease activity index)score changes,adverse reactions occurred rate and clinical efficacy of two groups were compared.Results After treatment of group A was treated with PE,laboratory indicators except IgM(t =0.509,P =0.612),other indexes were significantly decreased,differences were statistically significant (t =29.447,186,56.447,41.867,12.841,92.675,92.980,all P 0.05),while IgG and ESR,bun,crea and replacement of the differences have statistical significance(t value were 28.999,194.9,40.634,40.634104.918, P value 0.05).Conclusion The clinical curative effect of virus inactivation of plasma replacement solution in treatment of severe SLE is better than that of albumin by Ringer's solution.

A Choice and Precautions of Replacement Fluids for Therapeutic Plasma Exchange / 대한수혈학회지

BACKGROUND: Therapeutic plasma exchange (TPE) is an effective and practical treatment for separation and removal of harmful antibodies or pathogenic substances from the blood. The volume of plasma removed must be replaced by a replacement fluid such as 4~5% albumin solution or Fresh frozen plasma (FFP). We conducted a study of coagulopathy using albumin solution and checked the chemical composition of fresh frozen plasma. METHODS: We measured pre- and post-TPE PT/aPTT for evaluation of the effect of albumin replacement on coagulation from 192 TPE sessions of 19 patients. We also investigated routine chemistry test items including glucose and electrolytes from 10 randomly selected FFP. RESULTS: The post PT and aPTT within four hours after TPE were prolonged due to a transient decrease in coagulation factors, but were normalized within 2 days after TPE. All coagulation time was corrected to the level of the pre-TPE status within four hours before the next TPE except the patients who received TPE 6 times or more. FFP showed higher level in glucose, sodium and inorganic phosphate. CONCLUSION: Albumin exchange produces temporary coagulation factor deficiency. However, this transient factor deficiency rarely causes clinical problems and the factors are rapidly corrected by redistribution and resynthesis. We should be careful about hypocalcemia, hyperglycemia, and hypernatremia when using FFP replacement.

Testify patient's blood electrolyte concentration a tendency to approach that of replacement-fluid in continuous renal replacement therapy / 中华危重病急救医学

Objective To prove with mathematical formula that the patient's blood electrolyte concentration shows a tendency to approach that of replacement-fluid after continuous renal replacement therapy (CRRT).Methods Electrolyte concentration of plasma,replacement-fluid and returning fluid were compared,and they were labeled as Cblood,Cnom,and Creturn respectively.The Creturn was calculated,and the relationship among them was demonstrated with comparison by mathematical formula.At last,according to their relationship,plasma change towards to the replacement fluid was analyzed.Results It was showed that Cblood＜Creturn＜Cnom or Cblood＞Creturn＞ Cnom,and according the relationship,it was derive that the trend of change in Cblood after circulation for m unit time was Cblood1 ＞Cblood2 ＞Cblood3 ＞ … ＞Cbloodm ＞Cblood or Cblood1 ＜ Cblood2 ＜Cblood3 ＜ … ＜Cbloodm ＜Cnom.The plasma electrolyte concentration would close to that of replacement fluid infinitely with the continue of CRRT.Conclusions With mathematical model,it is proved that the replacement fluid electrolyte concentration is the final target of the plasma.We must make up the replacement fluid correctly.And this results provide the basis for CRRT treatment of electrolyte disorder.

Clinical efficacy comparison of different replacement fluid for continuous hemofiltration in severe sepsis / 中国医师进修杂志

Objective To compare the clinical efficacy of three kinds of replacement fluid for continuous hemofiltration in severe sepsis,and to develop a more rational composition.Methods Fifty severe sepsis patients with continuous hemofiltration were divided into four groups randomly.The configuration of the replacement fluid in accordance with the random number table,randomly selected from four different formulations:group A (13 cases):Ports composition provided by Nanjing general hospital;group B (12 cases):Zhongshan hospital composition; group C (11 cases):an improved composition; group D (14 cases):an improved composition by Donghua hospital affiliated to SUN Yat-sen university.Blood electrolytes,blood gas analysis,renal function,blood glucose(highest and lowest serum glucose in treatment period),high sensitive C-reactive protein(hs-CRP) concentration,calcium concentration in filter were tested before and after every treatment period.Results The concentration of blood electrolytes during treatment had no significant change (P ＞ 0.05).Renal function were improved significantly after treatment among four groups (P ＜ 0.05).The level of hs-CRP decreased significantly after treatment (P ＜ 0.05) and there was no significant difference among four groups (P ＞ 0.05).The change of serum glucose during treatment was the smallest in group D than that in group A,B,C [(3.0 + 0.9) mmol/L vs.(11.2 + 2.0),(3.8 + 1.1),(5.5 +1.3) mmol/L](P ＜ 0.05).Calcium concentration in filter was the lowest in group D than that in group A,B,C [(1.5 + 0.5) mmol/L vs.(2.0 + 0.7),(2.3 + 0.5),(2.1 + 0.4) mmol/L] (P ＜ 0.05).The dosage of heparin was the least during treatment in group D than that in group A,B,C[(6.5 ± 2.8) U/(kg·h) vs.(8.9 ± 3.4),(7.9 ± 3.0),(8.7 ± 3.1) U/ (kg· h)] (P ＜ 0.05).Conclusions Improved composition by Donghua hospital affiliated to SUN Yat-sen university hospital compared to other compositions can better maintain a stable blood glucose levels,have a better anticoagulant effect,reducing the application of heparin,maintain a stable homeostasis.It is worthy of using in clinic.

Influence of replacement with Ringer's lactate for preoperative NPO deficits on blood glucose concentration in children undergoing strabismus surgery

BACKGROUND: We investigated the effect that replacement with Ringer's lactate (RL) for preoperative NPO deficits might have on blood glucose concentration in children undergoing strabismus surgery. METHODS: Sixty children scheduled for strabismus surgery were enrolled in this study and RL was administered to all subjects for replacement of preoperative NPO deficits.Patients were randomly assigned to three groups according to the types of maintenance fluid employed during anesthesia.RL, 5% dextrose in one-fourth strength normal saline (D51/4NS), and an equal volume of D(5)1/4NS and RL each were used as maintenance fluids for Group 1, 2, and 3, respectively.After glycopyrrolate 0.004 mg/kg IV, anesthesia was induced with propofol 3 mg/kg and rocuronium 0.6 mg/kg.After tracheal intubation, anesthesia was maintained with 2-3 vol% sevoflurane in 50% air with oxygen.Blood glucose concentrations were checked from blood samples through a 22 gauge catheter inserted into a saphenous vein at the time of induction, 30 and 60 min after induction of anesthesia. RESULTS: There were no significant differences in baseline blood glucose levels at the time of induction of anesthesia among three groups.And the mean blood glucose concentrations remained unchanged throughout the study period in all groups.None of the patients were found to be hypoglycemic or hyperglycemic throughout the study period. CONCLUSIONS: This study shows that the replacement of preoperative NPO deficits with RL maintains the blood glucose concentration within physiological range throughout the operation and anesthetic recovery phase, regardless of the types of maintenance fluid.

Ocular Toxicity of Miconazole in Vitreous Replacement Fluid

To determine the ocular toxicity of intravitreal miconazole, we conducted a controlled trial in 20 pigmented rabbit eyes(10 rabbits). An anterior chamber paracentesis was performed on all animals and 0.4 ml of perfluoropropane(C3F8) gas was injected intravitreally. On day three, when it was fully expanded, eyes were underwent C3F8/fluid exchange with vitreous replacement fluid. The infusion solution contained various amounts of miconazole, 0.5 microgram/ml. 1 microgram/ml, 5 microgram/ml, 10 microgram/ml, 50 microgram/ml, 100 microgram/ml and normal saline for control. Intravitreal infusion was performed for 25-30 minuteds and a total of 100-120 ml of fluid was replaced. Histopathological examination revealed retinal toxic reactions in concentrations of 10 microgram/ml or greater. This study suggests that infusion solution of 5 microgram/ml or less is the concentration exceeds the minimal inhibitory concentration for most of fungi and may be safetly used in the treatment of fungal endaphthalmitis.