40．海脉素
出处：按学科分类—医药、卫生 军事医学科学出版社《临床常用进口药物手册》第209页（15156字）
【中文释文】：
3．5%胶体输注溶液容量替代品
有效成分：血脉素(Polygeline)
〔成分〕
1000ml含有：
通过尿素桥(相当于6．3g氮)
交联的明胶降解明胶多肽(来源于牛骨) 35g mmol g
氯离子 145 5．14
钾离子 5．1 0．20
钙离子 6．25 0．25
钠离子 145 3．33
微量的磷酸根离子和硫酸根离子，及带负电荷至等渗点的多肽
注射用水 加至1000ml
物理化学参数：
平均分子量 30000道尔顿(1)
相对粘滞度(35℃) 1．7～1．8
输注溶液的pH值 7．3±0．3
胶凝点 低于3℃
〔包装规格〕
10瓶塑料瓶输注液的临床包装，每瓶500ml。
24瓶塑料瓶输注液的临床包装，每瓶500ml。
〔以适应证分类的药品〕
输注溶液，容量代用品。
〔适应证〕
海脉素是一种容量代用品，用于纠正或预防血浆／全血容量缺乏引起的循环功能不全，包括绝对性(如由出血引起)和相对性(如由于血容量在循环各腔室间移动引起)。
海脉素适用于以下方面：
低血容量性休克；
全血或血浆丢失(如由于创伤、烧伤、术前自体输血或供献血浆引起)；
充填心肺循环机。
另外，海脉素可用作各种药物的输注溶剂。
〔禁忌证〕
已知对该制剂组成成分产生过敏反应者。已存在严重过敏反应者。
以下情况，海脉素仅可以在严格控制的范围内应用，如果医生认为有必要输注，给药应特别谨慎：
所有血管内容量增多及其结果(如每搏输出量增多，血压上升)、组织间液容量增多或血液稀释等情况下给药可给病人带来特殊的危险性。
这些情况常见于：充血性心力衰竭、高血压、食管静脉曲张、肺水肿、出血素质、肾性及肾后性无尿。所有具有组织胺释放高危因素的病人(如过敏者或有组织胺反应史的病人)。
后一种情况，海脉素只可以在给予适当的预防措施后应用(见给药中的注意事项)。
此制剂的应用对孕妇和哺乳期的妇女不是禁忌，但一般来说，妊娠期间和刚刚结束之后，使用容量代用品液体应予特别护理。
〔给药中的注意事项〕
像所有输注溶液一样，由于生理原因，海脉素不能在冰冷状态下输入。
溶液仅能在清亮状态下输注。
组织胺释放引起的反应可以通过预防性使用H1和H2受体阻断剂(如静脉注射二甲吡茚0．1mg／kg和静脉注射甲氰咪呱0．5mg／kg)来避免。
由于技术原因，容器中留有一定量的空气，因此，用塑料输液瓶加压输液必须在控制下进行，因为不能完全排除产生空气栓塞的危险。
〔与其它药物的相互作用〕
使用强心甙的病人，应考虑到海脉素中的钙剂与其具有协同作用。
〔剂量，用法和输注时间〕
通常情况下的剂量：
剂量及输注速度可按照个体情况调整并应特别依据通常的循环参数(如血压)来决定。
作用程度和持续时间依输注量、输注速度和存在的容量缺乏程度而定。
对于健康的成年人，以下输注量为宜：
全血及血浆丢失
预防休克 500～1500ml
容量缺乏性休克 最多2000ml
急救 按所需要量
血压可作为参考指标。
如果血液的主要成分稀释后仍保持在临床限值以上，并无高血容量和水分过多出现，则上述剂量可补充得更多一些。
一般来说，当红细胞压积降至25%以下时，必须立即考虑给予浓缩红细胞或凝血因子。
对婴儿及老人应注意，这类病人蛋白储备不足。
〔给药方法〕
海脉素是一种现成可用的静脉注射溶液，输注速度和持续时间应按照病人需要而定。
输注速度应按照监测的血压值调整，滴速可使用下列公式计算：
如：500ml液体要在1h内输入
急救时，海脉素可快速输注(如5～15min内输入500ml)。
〔副作用〕
若发生药品说明书中未提及的副作用，请您及时通知您的医师或药师。
在此容量代用品输注中及输注后，偶可出现一过性皮肤反应(荨麻疹、风团)、低血压、心动过速、心动过缓、恶心呕吐、呼吸困难、体温升高和／或寒战。
罕见有休克状态的严重过敏反应病例。若发生时，依据副作用的性质和严重程度进行处理。如果出现副作用，应立即停止输注，若需要，应按下述原则处理：
轻微反应：给予抗组织胺药物。
严重反应：如果适宜，立即缓慢静脉注射儿茶酚胺，加用大剂量的皮质类固醇(缓慢静脉注射)、容量代用品、吸氧。
现已证实组织胺释放是输注海脉素产生过敏性副作用的原因。
输注速度过快可促发组织胺介导的过敏反应。
另外，出现上述反应可能是由于数种促组织胺释放药物累积引起的结果(如麻醉药、肌肉松弛药、镇痛药、神经节阻断剂、抗胆碱能药物)。
〔贮存和稳定性〕
海脉素贮存在2～25℃，该溶液过期后不能使用。包装箱及容器上均有终止日期，若海脉素贮存在25℃以上，该终止日期应减去2年。
一旦输液瓶被打开，任何未用的内容物均弃掉。请存放于儿童不易接触的地方。
〔补充资料〕
海脉素是一种淡黄色透明的多肽溶液。
此制剂不含防腐剂，冻结及融化均不影响其物理化学特性。
组织化学，放射化学和组织学研究均显示海脉素不在网状内皮系统蓄积，即使用大剂量时亦未发现器官功能障碍。
对肾功能未受损的病人，从输注结束到海脉素完全排出体外，正常需要48h，而对透析的病人，若海脉素未被完全排出体外，则被内源性蛋白酶降解。
海脉素的输注可导致血液稀释并因此而降低血液粘度，这样可以改善微循环。
海脉素无致免疫性，因而不会诱发抗体形成。海脉素不会导致任何物质特异性凝血功能损伤，但如果输入量相对过多，应注意可能稀释血液系统内的成分，但血小板的功能不受影响，海脉素不会影响血型鉴定。
〔注意〕
由于海脉素中钙含量较多，使用后短期内可出现血清钙浓度轻度升高，特别是在大剂量海脉素快速输注时。迄今为止，输注海脉素后导致高钙血症的临床病例尚未见报道。
采用两个静脉通道同时分别输注海脉素和经枸椽酸抗凝剂处理过的全血，不会产生副作用，再钙化仅出现于海脉素与其他物质在体外配伍并于同一静脉通道输注时。而肝素化的血可与海脉素混合。谨慎消毒的同时，也应注意海脉素不但可与常用的输注溶液(盐水、葡萄糖、林格液等)混合，而且可与心血管药物、皮质类固醇、肌肉松弛药、巴比妥类、维生素、链激酶、尿激酶、青霉素系列和头孢氨噻肟等抗生素相混合，当然前提是它们可溶于水。输注海脉素可导致暂时性红细胞沉降率加快。
〔生产厂商〕
德国马堡贝林大药厂
(附本品别名：血代)
【外文释文】：
3．5%Colloidal Infusion Solution for Volume Substitution
Active ingredient：Polygeline
Composition
1000 ml contain：
Polypeptides of degraded gelation(origin：
bovine bone)，cross-linked via urea bridges 35g
(equivalent of 6．3g of nitrogen) mmol g
chloride ions 145 5．14
potassium ions 5．1 0．20
calcium ions 6．25 0．25
sodium ions 145 3．33
Traces of phosphate ions and sulphate ions，plus anionic polypeptides up to the isoionic point．
Water for injections ad 1 000 ml
Physico-chemical data：
Mean molecular weight 30 000 Dalton%(2)
Relative viscosity(35℃) 1．7-1．8
pH of the infusion solution 7．3±0．3
Gel point below 3℃
Presentatin and contents by weight，volume or number of intems
Clinic pack of 10 plastic infusion bottles
each containing 500ml
Clinic pack of 24 plastic infusion bottles
each containing 500ml
Substance or indication category
Infusion solutions，volume replacement
Indications
Haemaccel is a plasma substitute for volume replacement used to correct or avert circulatory insufficiency due to plasma／blood volume deficiency，absolute(e．g．resultin from bleeding)or relative(e．g．resulting from a shift in plasma volume between the circulatory compartments)：
·Hypovolaemic shock
·Loss of blood and plasma(e．g．due to trauma，burns，autologous blood or plasma donation before an operation)
·For filling the heart-lung machine
In addition Haemaccel can be used as a vehicle for various drugs．
Contraindieations
Known hypersensitivity to constituents of the preparation．Existing severe allergic reactions．
In the following cases，Haemaccel is indicated to a restricted extent only．If the physician considers the infusion necessary，it should be given taking special precautions：All conditions in which an increase in intravascular(blood vessel)volume and its consequences( e．g．increased stroke volume，elevated blood pressure)，or an increase in interstitial fluid volume or haemodilution could represent a special risk for the patient．Examples of such conditions are：congestive heart failure，hypertension，oesophageal varices，pulmonary oedema，haemorrhagic diathesis，renal and post-renal anuria．
In all patients at an increased risk of histamine release(e．g．persons with allergic／allergoid reactions and patients with a history of histamine response)．
In the latter cases Haemaccel may be given only after taking appropriate prophylactic steps(see Measures of precaution for administration)．
Use of the preparation in pregnant women and nursing mothers is not contraindicated．Generally，however，particular care should be exercised when fluid or volume replacements are administered during or immediately after pregnancy．
Measures of precaution fo administration
For physiological reasons Haemaccel should not be infused in the cold state，like all infusion solutions．
Infuse clear solutions only．
Reactions caused by histamine release can be avoided by the prophylactic use of H1 and H2 receptor antagonists(e．g．dimetinden 0．1mg／kg of body weight i．v．and cimetidin 5mg／kg of body weight i．v．)．
For technical reasons there is a residual air volume in the container．Thus，pressure infusions with the plastic infusion bottle must be carried out under controlled conditions only，as the risk of an air embolism can not be excluded．
Interactions with other agents
In the case of patients receiving cardiac glycosides，the synergistic effect of the calcium in Haemaccel should be taken into account．
Dosage instruction，mode and duration of administration
Dosage，unless otherwise prescribed：
The dosage and infusion speed are to be adjusted according to the individual situation and will depend inter alia on the usual circulatory parmeters(e．g．blood pressure)．
The extent and duration of the effect achieved depend on the infusion volume，the infusion speed and the existing volume deficit．
For healthy adults the following volumes are considered appropriate：
blood or plasma loss
shock prophylaxis 500--1500ml
volume deficiency shock up to 2000ml
in emergencies volume as required
The blood pressure is the parameter of reference．
The above volumes may be even higher，provided that the essential elements of the blood are maintained above the critical limit of dilution and that hypervolaemia and hyperhydration are avoided．
Generally，at the latest the administration of red cell concentrate or coagulation factors must be considered when the haematocrit falls below 25% by volume．
Note that in the case of babies，infants and elderly persons such patients have inadequate reserves of protein．
Mode of administration
Haemaccel is a ready-for-use solution to be infused by the intravenous route．The speed and duration of the infusion depend on the needs of the patient．
The infusion speed is to be adjusted in accordance with the monitored blood pressure values．The drip rate can be calculated using the following formula：
e．g．：500 ml to be infused in 1 hour：
In emergencies it is possible to administer Haemaccel as a rapid infusion(e．g．500 ml in 5 to 15min)．
Side-effects
If you develop side-effects which are not mentioned in this package insert，please inform your doctor or pharmacist．During or after the infusion of plasma substitutes，transient skin reactions(urticaria，wheals)，hypotension，tachycardia，bradycardia，nausea／vomiting，dyspnoea，increases in temperature and／or chills may occasionally occur．
Rare cases of severe hypersensitivity reactions reaching as far as life-threatening shock have been observed．Here，the treatment required depends on the nature and severity of the side-effect．
If side-effects occur the infusion should be discontinued at once．If necessary，treatment should be given as follows：Mild reactions：Administer antihistamines．
Severe reactions：If appropriate，immediately inject catecholamines slowly i．v．，plus high doses of corticosteroids slowly i．v．，volume replacement，oxygen．
Histamine release has been shown to be the cause of anaphylactoid side-effects associated with infusions of Haemaccel．
Histamine-induced reactions can be encouraged by rapid infusion．
Furthermore，the above-described reactions may occur as a result of the cumulative effect of several histamine releasing drugs(e．g．anaesthetics，muscle relaxants，analgetics，ganglia blockers and anticholinergic drugs)．
Storage and Stability
Haemaccel should be stored at 2-25℃．The solution must not be used after the date of expiry given on the pack and container．If Haemaccel is stored at above 25℃ the stated expiry date has to be reduced by 2 years．
Once an infusion bottle has been opened，any unused contents are to be discarded．
Store out of reach of children!
Additional information
The preparation contains no preservative．Freezing and thawing do not result in a change in its physicochemical properties．
Histochemical，radiochemical and histological studies have shown that Haemaccel is not stored in the RES．Disturbances of organ functions have not been observed even at high dosages．
In patients with intact renal function polygeline is normally fully excreted 48 hours after the edn of the infusion．If，for example in dialysis patients，the polygeline cannot be excreted adequately，it will be degraded by endogenous proteases．
Infusion of Haemaccel leads to haemodilution and thus lowers the viscosity of the blood．This can result in an improvement of microcirculation．
Administration of Haemaccel does not induce antibody formation．
Haemaccel does not lead to a substance-specific impairment of coagulation or platelet function．However，if large amounts are infused，haemodilutional effects on the coagulation potential occur．
Blood-grouping tests are not affected by polygeline．
Notes
Due to the raised calcium content of Haemaccel，the serum calcium concentrations may be found to be slightly elevated for a temporary period-especially when large amounts of Haemaccel are administered by rapid infusion．So far no reports have been received of cases involving clinical signs of hypercalcemia resulting from an infusion of Haemaccel．
In case of simultaneousadministration of Haemaccel and blood，anticoagulated with citrate，into separate venous accesses，no adverse reaction is to be expected；recalcification due to the calcium ion content in Haemaccel can only occur when Haemaccel is mixed with other substances or if subsequent infusions are given using the same venous access．Heparinized blood，however，can be mixed with Haemaccel．
Taking sterile precautions，Haemaccel can be mixed with the usual infusion solutions(saline，glucose，Ringer’s solution，etc．)as well as with cardiovascular drugs，corticosteroids，muscle relaxants，barbiturates，vitamins，streptokinase，urokinase，antibiotics of the penicillin series and cefotaxime，provided that these are soluble in water．
The infusion of Haemaccel may result in a temporary increase in the erythrocyte sedimentation rate．
Manufacturer
Behring werke AG Marburg，Faderal Republic of Germany