危重患者胶体复苏的有效性和安全性

尽管已有临床研究和荟萃分析的证据表明在危重患者中使用胶体复苏和晶体复苏同样有效，而且有来自于高水平的临床试验和荟萃分析的报告称，使用羟乙基淀粉（hydroxyethylstarch，HES）溶液会出现肾毒性反应、出血风险增加以及死亡率增高的趋势，但胶体治疗依然流行，在世界范围内HES溶液的使用与日俱增。我们主要探讨使用胶体的优势，即胶体是比晶体更为有效的血浆扩容剂、合成胶体与白蛋白一样安全、HES溶液在合成胶体中的风险／效益比最优而且第三代的HES130／0．4比前两代HES不良反应发生率更低等。临床研究表明用晶体溶液达到类似复苏效果的用量比通常认为的要少，即少于2倍胶体用量。白蛋白对于闭合性脑损伤以外的重症监护室（intensiveunitcare，ICU）患者安全性都很高。所有的合成胶体，如右旋糖酐、明胶和HES等都有剂量依赖的副作用，例如凝血障碍、肾衰竭和组织蓄积。在严重脓毒症患者中使用大剂量HES可能导致过高的死亡率。第三代HES130／0．4副作用更小的假设目前还未经证实。有关HES130／0．4的临床试验有着显著缺陷，主要因为并未针对ICU或急诊科患者；仅有24—48小时的短暂观察期；累积使用剂量小于每日剂量限值（50ml／kg）；并且使用了不合适的对照液体如其他HES溶液或明胶。总之，首选胶体溶液对急性血容量减少的患者进行复苏治疗的理论缺乏临床证据的支持。基于给药剂量的限制，合成胶体治疗危重成人及儿童患者的效果并非有益而是有害。安全剂量需通过对高风险患者进行长达90天观察期的研究来确定。尽管HES130／0．4的使用日益增加，但是它还缺乏研究证实。由于有晶体作为等效并且更为安全的选择方案，因此除进行临床研究外应避免使用胶体。

Despite evidence from clinical studies and meta-analyses that resuscitation with colloids or crystalloids is e- qually effective in critically ill patients, and despite reports from high-quality clinical trials and meta-analyses regarding neph- rotoxic effects, increased risk of bleeding, and a trend toward higher mortality in these patients after the use of hydroxyethyl starch （HES） solutions, colloids remain popular and the use of HES solutions is increasing worldwide. We investigated the major rationales for colloid use, namely that colloids are more effective plasma expanders than crystalloids, that synthetic colloids are as safe as albumin, that HES solutions have the best risk/benefit profile among the synthetic colloids, and that the third-generation HES 130/0.4 has fewer adverse effects than older starches. Evidence from dinical studies shows that compa- rable resuscitation is achieved with considerably less crystalloid volumes than frequently suggested, namely, 〈2-fold the vol-ume of colloids. Albumin is safe in intensive care unit patients except in patients with dosed head injury. All synthetic colloids, namely, dextran, gelatin, and HES have dose-related side effects, which are coagulopathy, renal failure, and tissue storage. In patients with severe sepsis, higher doses of HES may be associated with excess mortality. The assumption that third-generation HES 130/0. 4 has fewer adverse effects is yet unproven. Clinical trials on HES 130/0.4 have notable short- comings. Mostly, they were not performed in intensive care unit or emergency department patients, had short observation pe- riods of 24 to 48 hours, used cumulative doses below 1 daily dose limit （50 ml/k~）, and used unsuitable control fluids such asother HES solutions or gelatins. In conclusion, the preferred use of colloidal solutions for resuscitation of patients with acute hypovolemia is based on rationales that are not supported by clinical evidence. Synthetic colloids are not superior in critically ill adults and children but must be considered harmful depending on the cumulative dose administered. Safe threshold doses need to be determined in studies in high-risk patients and observation periods of 90 days. Such studies on HES 130/0.4 are still lacking despite its widespread and increasing use. Because there are safer and equally effective alternatives in the form of crvstalloids, use of synthetic colloids should be avoided except in the context of clinical studies.