Recent advances in the pharmacotherapy for hyperbilirubinaemia in the neonate

Jaundice is a common cause for diagnostic works-up and therapeutic intervention in neonates. This is motivated by the risk for severe neurological sequelae (kernicterus). The mainstays of treatment for the past decades have been exchange transfusion and phototherapy. Exchange transfusion is now becoming rare due to immune prophylaxis in Rhesus-negative women, and treatment of sensitised infants with intravenous immunoglobulin. Several different pharmacological approaches have been studied as far as the treatment of neonatal jaundice. Of these, the focus of attention in recent years has been on the haem oxygenase inhibitors (metal meso- and protoporphyrins). These are effective inhibitors of bilirubin production and have been shown to significantly reduce peak serum bilirubin levels in several clinical trials, both when used prophylactically and therapeutically. However, questions remain regarding long-term safety, as well as the advisability of whole-scale inhibition of bilirubin production. Nevertheless, in selected infants with a high risk of severe jaundice, the use of haem oxygenase inhibitors may be acceptable. Pharmacotherapy in jaundiced infants is fraught with risks, as many drugs may increase the entry of bilirubin into the brain and presumably, the risk for neurotoxicity. Both the displacement of bilirubin from its albumin binding and interference with the function of phosphoglycoprotein in the blood-brain barrier are documented mechanisms in this respect.     

Management of neonatal hyperbilirubinaemia and prevention of kernicterus.

Hyperbilirubinaemia remains one of the most common and more important pathological conditions in the newborn. The possibility that the so-called physiological or developmental hyperbilirubinaemia, with relatively low levels of serum bilirubin, could be responsible for bilirubin encephalopathy in the small premature infant is of great concern to the neonatologist; premature newborns are prone to developing hyperbilirubinaemia. Current methodologies for suppressing severe neonatal jaundice include: (a) attempts to stimulate liver conjugating enzymes using drugs such as phenobarbital; (b) attempts to degrade bilirubin with phototherapy; and (c) exchange transfusion. It is too soon to consider tin-protoporphyrin as a drug for the prevention and treatment of neonatal hyperbilirubinaemia. However, if it can be shown that tin-protoporphyrin can serve as a safe and less costly alternate treatment, a considerable improvement in the management of neonatal jaundice would be achieved.     

换血治疗新生儿重症溶血病的护理

目的探讨换血疗法治疗新生儿重症溶血病的最佳护理措施。方法采用外周动静脉同步换血疗法,加强术前、术中及术后的监护,采取相应的护理措施。结果46例重症溶血病的患儿换血后血清胆红素明显下降,换血后无并发症发生。结论重症溶血病的患儿一经入院,护士即应作好换血疗法的急救准备,统筹安排时间,做好严密的监护,才能赢得抢救时机,减少并发症的发生。     

新生儿高胆红素血症471例临床分析

目的 分析新生儿高胆红素血症的高危因素,建立重点监测、及早发现和早治疗病理性黄疸的方法,减少胆红素脑病的发生.方法 选取2012年5月至2013年4月我院新生儿科收治的471例新生儿高胆红素血症患儿,回顾性分析新生儿高胆红素血症的病因和3例胆红素脑病的临床资料.结果 本研究中,新生儿高胆红素血症已明确病因的排位依次是围生因素（54.99％）、血液系统方面的原因（12.74％）、感染（4.46％）;3例胆红素脑病的病因无一例是溶血性疾病,与围生因素和家长不重视有关.结论 新生儿黄疸是新生儿期常见的疾病,14.52％患新生儿高胆红素血症（这个比例比实际低）,不及时治疗会发生胆红素脑病,留下后遗症,影响预后.从孕期开始对家长进行黄疸知识的普及,新生儿科医生进驻爱婴区查房,对存在高危因素的婴儿重点监测,对出院病人动态随访,是早期发现新生儿高胆红素血症和预防胆红素脑病的最有效预防干预措施;对高胆红素血症应尽早采取首选光疗加药物辅助治疗的综合方法,减少胆红素脑病的发生.     

新生儿黄疸治疗进展

本文探讨目前新生儿黄疸治疗常用的蓝光照射、换血疗法、酶诱导剂、微生态制剂、茵栀黄制剂等治疗方法的应用指征、临床疗效及利弊,临床工作中,新生儿黄疸的干预方案应建立在病史、病程、体检和权衡利弊的基础上,对患儿尽早给予相应的干预治疗,可有效实现降低高胆红素血症以及胆红素脑损伤患病率的目的 。     

外周动静脉同步换血治疗新生儿高胆红素血症的临床研究

目的 评价外周动静脉同步换血疗法治疗新生儿重症高胆红素血症的效果及安全性,探讨其适应症及对临床的指导意义.方法 采用外周动静脉同步换血术治疗96例高间接胆红素血症患儿,比较其换血前后血常规、胆红素、电解质、凝血功能及血糖水平的变化,监测换血后神经系统症状体征及血常规、胆红素的变化情况.结果 换血术后血清总胆红素平均下降48.6%,以间接胆红素为主,白细胞、血小板、血钾均有下降(P<0.01),红细胞、血红蛋白及血糖明显上升(P<0.01),血钙、钠、镁及氯无明显变化(P>0.05),纤维蛋白原下降(P<0.01),异常的活化部分凝血酶原时间恢复正常.凝血酶原时间及凝血酶时间无明显变化(P>0.05),术中有个别病例发生呼吸减慢及心血管功能障碍,术后有坏死性小肠结肠炎发生.结论 外周动静脉同步换血疗法疗效好,安全性高,操作简单,但术中术后的严密监测仍是必要的.     

新生儿溶血病诊疗体会

目的 总结新生儿溶血病的治疗方法,以减少新生儿高胆红素脑病的发生,避免或减少换血治疗.方法 对60例新生儿溶血病的临床资料进行回顾性分析.结果 60例新生儿溶血病中,ABO溶血55例,Rh溶血5例,黄疸消退时间6～7天,平均住院时间8天,全部病例均治愈,1例予换血疗法,无一例发生胆红素脑病和死亡,无严重并发症及后遗症的发生.结论 对存在母婴血型不合的新生儿应早筛查、早诊断、早治疗.双面蓝光照射、酶诱导剂应用、洗肠、纠正酸中毒、大剂量白蛋白及丙种球蛋白应用等是治疗新生儿溶血病的有效方法,可有效降低换血治疗的风险及并发症.     

新生儿黄疸动态监测及早期干预治疗疗效观察

目的 评价新生儿黄疸动态监测的意义及早期不同干预治疗的临床疗效。方法 对新生儿进行早期黄疸动态监测, 将动态监测中发现胆红素超标的患儿随机分成蓝光治疗组、蓝光辅助茵栀黄治疗组、蓝光辅助妈咪爱(枯草杆菌二联活菌)治疗组和对照组, 通过比较各组胆红素脑损伤的发生率及胆红素值的下降程度, 客观评定新生儿早期黄疸监测的临床意义及不同干预治疗的临床疗效。结果 治疗组黄疸峰值、高胆红素血症的发生率明显低于对照组, 差异有统计学意义(P<0.05)。与单一蓝光治疗相比, 蓝光治疗辅助茵栀黄或妈咪爱均能更有效降低胆红素值。结论 动态监测黄疸可尽早发现胆红素水平的异常, 为尽早干预治疗提供了保障。早期联合治疗能更有效降低胆红素, 有效预防新生儿胆红素脑损伤的发生。     

Haem arginate: a new stable haem compound

Intravenous administration of haem in acute hepatic porphyrias inhibits the induction of delta-aminolaevulinic acid synthase, reduces the formation of potentially harmful metabolites of porphyrin synthesis and corrects the haem deficiency. Typically, haem therapy has been given in the form of haematin--haem dissolved in alkali. Such haematin solutions are, however, extremely unstable. Thus, the rapid decomposition of this therapeutic agent may have been responsible for the ineffectiveness of treatment in some clinical states and adverse reactions may have been caused by haematin degradation products. There is, therefore, a need for a stable, effective and well-tolerated haem preparation. We have prepared certain highly soluble haem compounds of which haem arginate has proved to be the most promising. Pure haemin was isolated from HIV and hepatitis B negative human blood. The haem derivatives prepared were screened as substrates for haem oxygenase. Haem arginate and haem lysinate were found to be as good substrates as methaemalbumin. Stock solutions of haem arginate were stable for 2 years at +6 degrees C. After dilution with sterile isotonic saline the haem arginate infusion was clearly more stable than haematin solutions made in the laboratory or prepared by dissolving commercial lyophilized haematin. The antiporphyrogenic effect of haem arginate (even after storage for two years) in 2-allyl-2-isopropylacetamide-induced experimental porphyria of rats was equal to that of freshly prepared haematin. The acute oral toxicity of haem arginate was low compared with the parenterally administered drug, indicating poor oral bioavailability. The acute toxic effects after high intravenous or intraperitoneal doses were directed to the liver.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of heparin injection on plasma protein binding of bilirubin and salicylate in rats

Intravenous heparin injection significantly increased the free bilirubin and salicylate fractions in the plasma of rats. This effect occurred within 2 min after injection of 500 U of heparin/kg and lasted for 15--45 min (bilirubin) or for greater than 45 min (salicylate). In vitro addition of heparin to plasma had no quantitatively significant effect on the protein binding of bilirubin and salicylate. The in vivo effect of heparin on protein binding was reversible by treating the plasma with activated charcoal, a procedure known to remove fatty acids from albumin. Since protein binding affects the pharmacokinetic characteristics and the pharmacological activity of drugs, the heparin--drug interaction may have significant clinical implications. Use of heparinized plasma for exchange transfusion in the treatment of neonatal jaundice may be hazardous.     

3M透明敷料在新生儿黄疸双面蓝光治疗中的应用价值分析

目的 探讨3M透明敷料在新生儿黄疸双面蓝光治疗中的临床应用价值.方法 选择新生儿黄疸者80例分为两组,各40例,所有患儿均采用双面蓝光治疗,对照组采用手套脚套包裹,观察组采用3M透明敷料覆盖,比较两组患儿新生儿胆红素脑病发生率、换血治疗率及皮肤破溃感染情况,并统计两组黄疸消退时间、照射蓝光时间及住院时间.结果 观察组新生儿胆红素脑病发生率、换血治疗率及皮肤破溃感染率均低于对照组（P＜0.05）;观察组黄疸消退时间、照射蓝光时间及住院时间均显著短于对照组（P＜0.05）.结论 3M透明敷料操作简单、安全有效,可达到缩短住院时间的目的.     

母乳性黄疸192例临床分析

目的：提高对母乳性黄疸的认识,以期早期诊断和治疗。方法：192例确诊为母乳性黄疸,新生儿血清总胆红素〈256μmol/L为轻度黄疸35例,血清总胆红素256～342μmol/L为中度黄疸114例。本组患儿轻、中度黄疸均不改变母乳喂养的频率及数量,间断给予轻度黄疸以光疗治疗,胆红素浓度过高者同时给予血浆或白蛋白辅助治疗。血清总胆红素〉342μmol/L为重度黄疸43例,给予间断光疗。结果：164例（80.2%）患儿在3d内血清胆红素降至原来水平的50%。结论：母乳性黄疸可导致高胆红素血症,及时干预可加速黄疸消退,其预后良好。     

新生儿高胆红素血症66例临床分析

目的探讨本地区新生儿高胆红素血症的病因,为预防及治疗提供依据。方法将66例高胆红素血症患儿分为换血组（33例）与未换血组（33例）进行病因分析,并对两组患儿的临床特点进行比较。结果两组高胆红素血症的病因均以溶血性因素为首,占62.1%（41例）,感染因素占22.7%（15例）,原因不明占15.1%（10例）。两组患儿在总胆红素浓度、发现黄染时间、就诊时间和黄疸持续时间等方面进行比较,差异有统计学意义（P〈0.001）。结论溶血与感染是新生儿高胆红素血症的主要原因,总胆红素浓度过高和干预延迟是引起高胆红素血症的高危因素。加强宣传,出院后的随访和及时就诊,是减少胆红素脑病发病的关键。     

茵陈蒿汤加味治疗婴儿黄疸69例的效果分析

目的探讨茵陈蒿汤加味治疗婴儿黄疸的临床效果。方法选择在本院中医科门诊就医的婴儿黄疸患者,单用茵陈蒿汤加味煎汤内服,10～15ml/次,3～4次,d,观察患儿二便的变化。结果患儿全部治愈,其中50例（72．50％）复查血清总胆红素、结合胆红素等项指标均降至正常值,或经皮测胆红素已正常;19例（27．50％）复诊或电话访问家长,婴儿皮肤黄疸消退,小便正常。结论茵陈蒿汤加味治疗婴儿黄疸,效果肯定,操作方便,不良反应少,临床可推广应用。     

Value of bile acid determination for the diagnosis of neonatal jaundice

Serum concentrations of bile acids and bilirubin, and activity of alanine transferase and alkaline phosphatase as well as bile acid and bilirubin levels in duodenal contents were determined in 90 infants aged 1-44 weeks (including 49 under 10 weeks of age) admitted to hospital for prolonged jaundice. Infants with extrahepatic cholestasis were found to have statistically higher serum bile acid and bilirubin concentrations. Oral administration of cholestyramine produced a statistically significant decrease in serum bile acids and bilirubin in infants with intrahepatic cholestasis under 10 weeks of age. In 24 out of the 30 infants with biliary tract obstruction total absence of bile acids in the duodenal contents was demonstrated while in the others the concentration did not exceed 0.2 mmol/l. The mean bile acid concentration in infants with intrahepatic cholestasis was 2.81 mmol/l while in 8 infants out of the 60 bile acids were either absent or present in trace amounts. The method had an 84.4% sensitivity.     

新生儿高胆红素血症外周动静脉换血疗法及护理

目的观察外周动静脉换血法治疗重症新生儿高胆红素血症的效果及采取的护理措施。方法对35例重症高胆红素血症患儿采用外周动静脉换血疗法,外周静脉输血,外周动脉抽血,均用输液泵控制,速度200～240ml/h。置辐射台上保暖,在换血的过程同时给予光疗。结果 35例患儿血清总胆红素在换血前为（552±101.2）μmol/L,换血后为（250.3±75.4）μmol/L,两者差异有统计学意义,P〈0.01,总胆红素换出率54.7%。结论输液泵控制的外周动静脉换血法简单、实用、安全,是治疗重症新生儿高胆红素血症的有效方法。优良的护理对提高换血的成功率,减少并发症起着重要作用。     

Effects of repeated intravenous administration of haem arginate upon hepatic metabolism of foreign compounds in rats and dogs.

Haem arginate is a new haem compound, recently introduced for the treatment of acute hepatic porphyrias. Porphyrias are characterized biochemically by decreased formation of haem due to defects in certain enzyme activities involved in the haem biosynthesis. Haem is essential for cell respiration and oxidative biotransformation. Hepatic drug metabolism, haem biosynthesis and catabolism were investigated after repeated intravenous administration of haem arginate in connection with toxicity studies. The daily doses of haem for rats were 4, 12 and 40 mg kg-1 and for dogs 3 and 9 mg kg-1 for 30 days and for 28 days, respectively. Hepatic microsomes were used in the assay of the following drug metabolizing enzymes: cytochrome P-450 and b5, aminopyrine N-demethylase, ethoxyresorufin O-deethylase and UDP-glucuronyl transferase. The assay of NADPH-cytochrome C-reductase and the enzymes reflecting synthesis and metabolism of haem in the liver (delta-aminolaevulinic acid synthase, delta-aminolaevulinic acid dehydratase, uroporphyrinogen I-synthase, uroporphyrinogen decarboxylase, haem synthase, haem oxygenase and biliverdin reductase) were performed from 20,000 g supernatants. The lowest dose administered to rats and dogs did not cause any significant changes compared to controls in the parameters measured. The highest doses significantly increased the activities of haem oxygenase and uroporphyrinogen I-synthase but decreased concentrations or activities of other enzymes, e.g. cytochrome P-450 and ethoxyresorufin O-deethylase. The results show that it is important to avoid overdosage of haem when restoration of mixed function oxygenase activity is needed.     

新生儿重症高胆红素血症外周动静脉同步换血法应用研究

目的探讨外周动静脉同步换血治疗新生儿重症高胆红素血症的疗效、安全性、适用性及对血液内环境的影响。方法采用股动脉、头皮静脉做换出、换入途径对15例重症高胆红素血症患儿进行同步换血,并对换血前后及换血后24h的多项指标进行监测。结果换血后总胆红素、间接胆红素明显下降(P<0.001),内环境影响小,多数变化指标换血24h内恢复或有不同程度回升。结论外周动静脉同步换血法疗效肯定,无明显并发症,值得推广。     

新生儿黄疸的治疗药物研究进展

新生儿黄疸是新生儿早期的一种生理现象,也是出生之后多种病理性疾病的临床表现之一。如不积极治疗,容易引起核黄疸等严重后遗症。药物治疗是新生儿黄疸的主要治疗手段之一。本文从抑制胆红素生成、加速胆红素转运、阻断胆红素肝肠循环、增加胆红素结合及促进胆红素排泄等不同环节,综述了新生儿黄疸的药物治疗进展,旨在为新生儿黄疸的防治及相关药物的临床合理应用提供参考。