治疗性血浆置换术中不良反应分析

目的 观察治疗性血浆置换术中不良反应与临床处置。方法 应用血细胞分离机行44次血浆置换，观察血浆置换过程中出现的不良反应。结果44次血浆置换术中出现20次不同程度的枸橼酸盐中毒，占45．5％。血浆过敏反应5次，占11．4％。血容量失衡1次，占2．3％。结论 血浆置换术中出现的不良反应主要有枸橼酸盐中毒、过敏反应和血容量失衡等。置换过程中注意观察和及时对症处理，能有效减少不良反应，保证血浆置换的顺利进行。     

血小板添加剂研究进展

使用血小板添加剂（PAS）部分或者全部替代血浆常温保存血小板具有许多优点，例如可以避免输注大量血浆引起的发热、过敏反应以及循环超负荷；另外可以改善保存环境使血小板活性与止血功能维持在较高水平，节省大量血浆用于其他目的，便于血小板制品病原体灭活等。近20余年来，对于血小板添加剂的研究一直是一个热点，不同配方的血小板添加剂不断有报道，对血小板的保护效果也越来越好。本文就对血小板添加剂的组成成分、各成分的作用、体内外保存效果等研究进展进行了综述。     

Effects of hypertonic saline, mannitol, and urea with regard to absorption and rebound filtration in cat skeletal muscle

OBJECTIVE: To study the effects of the hypertonic solutions 15% mannitol, 3% and 7.5% saline, and 30% urea at clinically relevant plasma concentrations with regard to absorption and rebound effects on tissue volume in skeletal muscle. DESIGN: A prospective, experimental study. SETTING: University laboratory. SUBJECTS: Twenty-eight anesthetized cats. INTERVENTIONS: The study was performed on an autoperfused and denervated cat calf muscle placed in a fluid-filled plethysmograph. Muscle volume changes and capillary filtration coefficient (reflecting capillary fluid conductivity) were measured before, during, and after intra-arterial infusion (4 mL/hr) of the hypertonic solutions. Mannitol and 3% saline have the same osmolality and were compared specifically in an attempt to distinguish osmotic effects from those specific to the compound. MEASUREMENTS AND MAIN RESULTS: All solutions reduced muscle volume during the infusion (p < .05). The maximum volume reduction persisted after 2 hrs of infusion for 3% and 7.5% saline, whereas there was a tendency for volume recovery during the urea infusion and a complete recovery back to control for mannitol. After discontinuation of the infusions, the muscle volume increased for all four solutions, stabilizing at the initial control for 3% and 7.5% saline, whereas it increased to levels above control for mannitol and urea (p < .05). Capillary filtration coefficient was increased by hypertonic saline (p < .05) but was unaffected by mannitol and urea. CONCLUSIONS: The effectiveness of a hypertonic solution in reducing tissue volume and its tendency to cause a rebound volume increase depends not only on the osmolality of the solution. Hypertonic saline may in the long run be superior to mannitol and urea to increase plasma volume or decrease tissue volume of an organ, because it lacks rebound effects. Alterations in capillary filtration coefficient (fluid conductivity) may reflect volume changes of the capillary endothelial cell and thereby differences in cell membrane permeability for the hypertonic solutions, also consistent with the obtained differences in tissue volume effects.     

Measurement of blood volume after haemodilution with haemoglobin-based oxygen carriers by a radiolabelled-albumin method

Recent studies have shown that the use of haemoglobin-based oxygen-carrying solutions (HBOCs) for perioperative haemodilution could significantly reduce the need for packed red blood cells in clinical practice. Though the effects of HBOCs on plasma volume have been characterized in experimental models of volume resuscitation from hypovolaemic shock, little is known about their action in normovolaemic haemodilution conditions. We therefore applied a radiolabelled serumalbumin method to determine blood volume after haemodilution with crosslinked or conjugated haemoglobin, in comparison with a reference solution of hydroxyethyl starch (HES). Three groups of New Zealand white rabbits were studied (n = 7 each group) subjected to moderate exchange transfusion with low molecular weight HES, bis(3,5-dibromosalicyl)fumarate crosslinked haemoglobin (alphaalpha-Hb), or dextran-conjugated haemoglobin (Hb-Dex-BTC). HES induced no changes in heart rate and blood pressure. The amplitude and duration of blood pressure increase and bradycardia were similar in both haemoglobin groups. A significant contraction of blood volume (12%) was observed 60 min after haemodilution with alphaalpha-Hb, compared to HES and Hb-Dex-BTC. At the same time point, a decrease in absolute haemoglobin (plasma haemoglobin x plasma volume) was also noted. This study suggests that in haemodilution conditions, the specific oncotic properties and circulating persistence of crosslinked and conjugated haemoglobin solutions affect the pattern of blood volume distribution differently.     

Do plasma substitutes have additional properties beyond correcting volume deficits?

The best strategy for volume therapy has been the focus of debate and there are still no unique accepted guidelines. There is increasing evidence that some plasma substitutes possess additional effects on organ perfusion, microcirculation, tissue oxygenation, inflammation, endothelial activation, capillary leakage, and tissue edema that are beyond their volume replacing properties. Whether the different plasma substitutes differ with regard this additional effects was reviewed. The additional effects of plasma substitutes have mostly been studied experimentally or in animals, much less results are available in humans. The results are not uniform ranging from beneficial to even detrimental effects of a certain volume replacement strategy. Some important results from the literature are not reflected in the actual recommendations for treating volume deficits in the critically ill: although crystalloids have been shown to have considerable negative effects on microcirculation, organ perfusion, tissue oxygenation, and endothelial integrity, they are still often recommended as first choice volume replacement strategy. In several experimental studies hypertonic solutions have been shown to have various beneficial effects, they have not been, however, translated into humans. In future, the choice of the ideal volume replacement regimen should not only be focused on its volume restoring properties, but additional effects (e.g. on organ perfusion on, tissue oxygenation, inflammation, endothelial activation, capillary leakage) should also be taken into account when treating hypovolemia in the critically ill.     

Can a bowel preparation exacerbate heart failure?

Polyethylene glycol solutions, used for bowel preparation before colonoscopy, in theory pass through the colon without any absorption of water. However, several investigators have reported that these solutions do increase plasma volume. This review compares polyethylene and sodium phosphate bowel preparations and their effects on patients with heart failure, and also offers recommendations for patients with heart failure who need colonoscopy.     

Plasma volume expansion after infusion of 5%, 20% and 25% albumin solutions in patients.

Fifty grams of albumin were infused into patients in the immediate post-operative period as either 5, 20 or 25% solutions. With all three solutions the increase in plasma volume was 500 ml or 11 ml/g of retained albumin, which is less than the normal water-binding capacity of albumin found in studies in vitro and in some clinical studies. This might be explained by a blocking of the water-binding capacity of the albumin or by the action of other unknown mechanisms, when albumin is given in an amount exceeding the losses. The expansion of the plasma volume did not depend on the concentration of the solutions given but only on the amount of albumin given and the deficit in plasma volume. Since albumin is a good plasma expander and a drug with a few secondary effects it is recommended in the treatment of shock. We prefer the 5% solution, which contains an electrolyte solution and is more easily infused, because of its low viscosity.     

A randomized, blinded trial comparing the hemostatic effects of pentastarch versus hetastarch

BACKGROUND: HES solutions provide a sterile, alternative colloidal fluid to albumin solutions and/or plasma in the management of patients who need plasma volume expansion. Solutions of HES are widely accepted internationally but are used only modestly in the United States, largely because of concerns over hemostasis. STUDY DESIGN AND METHODS: A randomized, blinded, two-arm trial comparing the hemostatic effects of pentastarch versus hetastarch when infused in the clinically relevant dose of 90 g of HES dissolved in 1.5 L of saline was conducted. Multiple studies of fibrin clot formation, fibrinogen/fibrinolysis, and platelet (PLT) functions were performed before and on multiple occasions for 70 days following HES infusion. RESULTS: Several significant abnormalities of hemostasis assay results occurred following HES infusions, with hetastarch causing significantly greater abnormalities than pentastarch. Individual clotting proteins and blood PLTs fell modestly because of plasma volume expansion and hemodilution. A fall in excess of that caused by hemodilution was demonstrated for von Willebrand factor antigen plus its associated FVIII and ristocetin cofactor activities. The partial thromboplastin time was prolonged, whereas the thrombin time was shortened. Plt function abnormalities were seen in most subjects to a modest degree. Studies of fibrinolysis were normal. CONCLUSIONS: Solutions of hetastarch produce significant abnormalities of some hemostasis laboratory results when infused at clinically relevant doses, but it is unlikely that the modest hemostatic abnormalities produced at these doses per se would lead to clinical bleeding. Hetastarch causes greater hemostatic abnormalities than pentastarch, and because both HES solutions have comparable plasma volume-expanding effects, it is reasonable to prefer pentastarch as a plasma volume expander.     

Risques potentiels du remplissage vasculaire

Blood volume expansion is the main treatment of hypovolemia, but may induce adverse effects. The risks of adverse effects are all the more high since the pre-load reserve of the patient is low. Adverse effects may be linked to the specific effects of the infused solutions, or directly induced by fluid loading. These latter complications may be due to the increase in hydrostatic pressure, an interstitial or a cellular edema, an induced hypothermia, or metabolic disturbances.     

Fluid replacement in hypovolaemia

Conclusions The question of which fluid should be used to augment a falling blood volume has been investigated in several animal models and numerous clinical trials. The results do not indicate an ideal approach. Generally electrolyte solutions are not as good as the other products. Because of the demands on the transfusion service for plasma procurement whole blood is in limited supply. However, whole blood should be available for large acute haemorrhages in excess of 2 l. The synthetic macromolecular colloids are probably as good as albumen solutions and fall into two clinical categories. The first group increase the blood volume by an amount slightly greater than the volume infused but are rapidly eliminated so their clinical effects remain for only two to three hours. Of these solutions the modified gelatins are probably the colloid of choice. For a more prolonged volume expansion of up to 24–36 h the larger macromolecules are more ideal but with a less potent initial oncotic effect [7]. Hydroxyethyl starch seems the most suitable of these substances. Albumen solutions are considerably more expensive but, otherwise have properties of volume expansion intermediate to the two colloid groups and limiting side effects of similar overall frequency. The final choice depends on local availability, cost effectiveness and personal clinical experience.     

An international view of hydroxyethyl starches

Hydroxyethyl starch (HES) is one of the most frequently used plasma substitutes. A variety of different HES solutions exist worldwide, which differ greatly in their pharmacological properties. HES is classified according to its manufactured or in vitro molecular weight (MW) into high MW (450–480 kDa), medium MW (200 kDa), and low MW (70 kDa) starch preparations. However, this is not sufficient, because as HES is metabolized in vivo, its MW changes, and it is the in vivo MW which is responsible for the therapeutic and adverse effects of each HES. The rate of metabolization depends mainly on the degree of hydroxyethyl substitution (ranging from 0.4 to 0.7), and the C2/C6 ratio of hydroxyethylation. A high degree of substitution and a high C2/C6 ratio lead to a slow metabolization of HES, resulting in a large in vivo MW. Slowly degradable high MW HES 450/0.7 and medium MW HES 200/0.62 have a high in vivo MW and are eliminated slowly via the kidneys. As a result, these starches have a relatively long-lasting volume effect. When infusing higher volumes ( > 1500 ml) are infused, large molecules accumulate in the plasma. This can result in bleeding complications due to decreased factor VIII/von Willebrand factor, platelet function defects, incorporation into fibrin clots, and an unfavorable effect on rheological parameters. Rapidly degradable medium MW HES 200/0.5 or low MW HES 70/0.5 are quickly split in vivo into smaller, more favorable molecule sizes, resulting in faster renal elimination, shorter volume effect, and fewer adverse effects on coagulation and rheological parameters. For historical and marketing reasons, only slowly degradable, high MW HES (480/0.7) is available in the United States. In Europe, a large variety of HES solutions are available, dominated by medium MW, easily degradable HES (200/0.5). Because of increasing international competition and the availability of newly developed starches, it is important to be aware of the pharmacological properties of HES and the advantages and disadvantages of the individual preparations. Received: 1 January 1998 Accepted: 17 August 1998     

Colloid solution therapy of experimental ischemic intestinal shock in rats

This study evaluated the effects of varying colloid concentrations and infusion volumes on survival and plasma volume expansion in rats subjected to an intestinal ischemic shock. Up to 10% solutions of albumin and dextran-40 in lactated Ringer's solution, infused over a 6-h period, had the same effects on hematocrit (Hct) changes and survival patterns. Mean Hct values (45% to 50%) were independent of colloid solution concentration. With lactated Ringer's solution alone, Hct was 55%, despite the very large volume used; and less than 3% of the infused lactated Ringer's solution remained as plasma volume at 3 and 6 h of infusion. With increasing colloid concentration a greater proportion of the infused volume contributed to plasma volume. Of a 10% colloid solution, 50% and 34% remained as plasma volume at 3 and 6 h. For colloid concentrations between 1% and 3%, there was an equal distribution of infused fluid between the extracellular fluid space and the plasma. Survival rate, as measured by blood volume expansion, was greater with colloid solution concentrations between 2% and 4%.     

Cardiocirculatory and biochemical effects of dextran 1.8% and ringer's lactate after minor surgical procedures.

The effects of dextran 1.8% in Ringer's lactate solution were compared with infusion of Ringer's lactate alone in two groups of 12 patients after minor surgical interventions. Plasma volume increased significantly only in the dextran treatment patients. We observed a marked hemodilution with both infusions, but all changes had disappeared after 24 hours. No adverse effects on the coagulation process, hepatic and renal function were noted. These results suggest that dextran 1.8% in Ringer's lactate is an effective and safe solution in plasma volume expansion for this type of patient.     

Efficiency of glutamyl peptide polymers as plasma volume extenders

A series of polymers of polyglutamic acid have been tested as plasma volume expanders. The results indicate that those polymers prepared from backbones of 40,000 molecular weight or over and side chains of 3,000 molecular weight or over, will have plasma volume retention half-life of 15 hours or longer. Measurements of the oncotic efficiency of these polymers in vivo indicated a blood stream fluid retention of approximately 51 ml./gm. of polymer. Similar measurements of polymer-serum albumin solutions in vitro showed a retention of 52 ml./gm. of polymer. The clinical response to infusion of solutions of these polymers indicated no untoward pharmacological properties. Although the number of trials presented is too small for ultimate conclusion regarding either the physiological or clinical effects of these polymers, they do provide a strong indication of the desirability of further clinical testing of this polymer and a sound basis on which to plan the larger scale preparation of polymer. Both measures are currently under way.     

Storage of platelets in a novel additive solution (M-sol), which is prepared by mixing solutions approved for clinical use that are not especially for platelet storage

BACKGROUND: To reduce adverse reactions due to platelet (PLT) transfusion, medical solutions on the market, such as saline and ACD-A, are used to replace the plasma of PLT concentrates in Japan; however, they are not strongly preservative. Here, an attempt was made to develop a novel additive solution (M-sol) having the ability to preserve PLTs stably, with only approved solutions for clinical use. STUDY DESIGN AND METHODS: M-sol is a mixture of solutions for medical use, which consists of 77 mmol per L NaCl, 3 mmol per L KCl, 1 mmol per L CaCl2, 21 mmol per L Na acetate, 15 mmol per L glucose, 9.4 mmol per L Na3 citrate, 4.8 mmol per L citric acid, 44 mmol per L NaHCO3, and 1.6 mmol per L MgSO4. The in vitro variables of PLTs stored in M-sol, Seto-sol, PASIIIM, or 100 percent plasma were compared during 14 days of storage. RESULTS: The in vitro parameters (pH, P-selectin, %hypotonic shock response, %disk, mean PLT volume, aggregability) of PLTs were better maintained in M-sol containing 3 percent plasma than in 100 percent plasma, PASIIIM with 31 percent plasma, and Seto-sol with 3 percent plasma during 14 days of storage. CONCLUSION: The 2-week storage of PLTs in M-sol is feasible in terms of the in vitro PLT function. Our results here show that the additive solution, with a high ability to preserve PLTs, can be prepared by mixing solutions approved for clinical use that are not specifically for PLT storage.     

亚甲蓝／光照法病毒灭活血浆的制备及应用评价

目的探讨亚甲蓝／光照法病毒灭活血浆的制备及其临床应用评价。方法随机抽取200份病毒灭活血浆,检测灭活前后的血浆容量、总蛋白、凝血因子及亚甲蓝的残余量;选取15756人份HBsAg、抗-HCV、抗-HIV酶联免疫吸附法检测阴性者的血浆,在病毒灭活前后分别进行HBV、HCV、HIV的核酸检测;临床随机抽取200例输注病毒灭活血浆的患者,观察病毒灭活血浆输注后是否出现输血不良反应。结果经亚甲蓝／光照法进行灭活处理的血浆,血浆容量达到（227．34±5．21）g,回收率达到（96．67±2．34）％;血浆总蛋白、血浆凝血因子（Ⅷ因子和纤维蛋白原）回收率分别达到（88．69±3．32）％,（86．84±2．16）％和（84．62±1．86）％,与处理前相比,差异无统计学意义（P〉0．05）;血浆经病毒灭活后亚甲蓝的残余量为（1．17±0．05）μmol／L,而过滤后残余量减少至（0．16±0．03）μmol／L,去除率达到86．32％;对15756人份血浆进行HBV、HCV、HIV核酸检测,发现HBV阳性23例,HIV阳性1例,阳性率为1．52‰,进行病毒灭活后,HBV、HCV、HIV核酸检测均为阴性。病毒灭活血浆输注人体后无不良反应发生。结论采用亚甲蓝／光照法进行病毒灭活的血浆,临床使用较安全;病毒灭活血浆能够有效降低经输血传播疾病的危险性,且不良反应较小。     

Plasma volume expansion and transcapillary fluid exchange in skeletal muscle of albumin, dextran, gelatin, hydroxyethyl starch, and saline after trauma in the cat

OBJECTIVE: To compare 5% albumin, 6% dextran 70, 3.5% gelatin, 6% hydroxyethyl starch 130/0.4, and saline regarding their plasma volume expanding effect after a surgical skeletal muscle trauma and their simultaneous effects on transvascular fluid exchange in skeletal muscle. DESIGN: Controlled, prospective, randomized laboratory study. SETTING: University research laboratory. SUBJECTS: Thirty-six adult cats. INTERVENTIONS: Systemic arterial pressure and tissue volume variations of and blood flow to a surgically isolated and autoperfused calf muscle placed in a plethysmograph were recorded. Arterial and venous pressures to the muscle were kept constant. After preparation, plasma volumes were determined by a I albumin tracer technique just before and 3 hrs after a bolus infusion of the plasma expander (25 mL/kg). MEASUREMENTS AND MAIN RESULTS: Plasma volume was 20.9 +/- 2.9 mL/kg (n = 36) just before infusion of the plasma expander (normal plasma volume for the cat is 34-37 mL/kg). The remaining volume expansion of the infusion after 3 hrs was 6.8 mL/kg for albumin, 11.2 mL/kg for dextran, 1.8 mL/kg for gelatin, 2.2 mL/kg for hydroxyethyl starch, and 0.9 mL/kg for saline. Plasma volume decreased by 1.1 mL/kg when no solution was given (n = 6 per group). Colloid osmotic pressure was better preserved with dextran and albumin than with the other solutions. Albumin and dextran reduced muscle volume by absorption after 3 hrs, whereas the initial absorption turned to net filtration in the gelatin and hydroxyethyl starch groups. Saline infusion increased muscle volume by filtration for about 20 mins, followed by an approximately constant volume. CONCLUSION: The relatively poor plasma expansion for all solutions analyzed can most likely be explained by increased transcapillary leakage due to increased microvascular permeability following trauma. Under such circumstances, for equal volumes, plasma expansion was better preserved with 6% dextran 70 than with 5% albumin, which was better than 3.5% gelatin, 6% hydroxyethyl starch 130/0.4, and saline.     

Pharmacokinetic-pharmacodynamic relationships of morphine in neonates.

Morphine pharmacokinetics and pharmacodynamics (analgesia and sedation) were evaluated after continuous intravenous infusion of morphine in 19 neonates, both preterm and term, whose lungs were ventilated to relieve respiratory distress. Elimination half-life, total plasma clearance, and volume of distribution (mean +/- SD) were 9.6 +/- 3.0 hours, 2.55 +/- 1.65 ml/min/kg (area analysis) or 2.09 +/- 1.19 ml/min/kg (steady-state data), and 2.05 +/- 1.05 L/kg, respectively, and were not significantly different in preterm and term neonates. In neonates with adverse effects of morphine, the plasma clearance was decreased twofold. Mean morphine concentration required to produce adequate sedation in 50% of patients was found to be 125 ng/ml, but concentrations above 300 ng/ml may be associated with adverse effects of morphine. Morphine-6-glucuronide was not detected in the plasma of any neonate, which may explain why neonates require high plasma concentrations of unchanged morphine for sedation.     

Comparison of the effects of a 50% exchange-transfusion with albumin, hetastarch, and modified hemoglobin solutions.

We compared the hemodynamic effects of replacing 50% of the blood volume of anesthetized rats with an equal volume of five solutions: human serum albumin (HSA), hetastarch, unmodified hemoglobin, diaspirin-crosslinked hemoglobin, and o-raffinose-crosslinked hemgolobin. Control rats were exchange-transfused with their own blood. HSA and hetastarch caused a severe reduction in systemic vascular resistance (SVR), hypotension, and acute renal failure immediately after the exchange-transfusion. Unmodified and diaspirin-crosslinked hemoglobins caused comparable and severe increases in SVR, whereas vasoconstriction induced by o-raffinose-crosslinked hemoglobin was minimal. The increased SVR induced by all hemoglobin solutions resolved over a 2-day period as the hemoglobin was cleared from plasma. Body weight was monitored for 5 days after the exchange transfusion as a measure of the relative long-term efficacy of the exchange solutions tested and increased substantially in control rats (that received blood). Rats that received both crosslinked hemoglobin solutions gained a comparable amount of weight as the control group. By contrast rats that received HSA, hetastarch and unmodified hemoglobin failed to gain weight or lost weight over the same period. In summary: i) HSA and hetastarch are relatively ineffective as resuscitative fluids when administered after the loss of a large volume of blood; ii) diaspirin-crosslinked hemoglobin causes severe vasoconstriction, comparable in intensity to that induced by unmodified hemoglobin; iii) o-raffinose-crosslinked hemoglobin induces minimal vasoconstriction; iv) the vasoactive effects of all hemoglobin solutions are reversible. We conclude, that of all solutions tested, both the short- and long-term effects of an exchange-transfusion with whole blood are most closely reproduced by an exchange with o-raffinose-crosslinked hemoglobin.