After this product was injected into the body, the average molecular weight of hydroxyethyl starch in plasma was 70,000-80,000 Daltons, which remained above the renal threshold during the treatment.
The distribution volume of this product is about 5.9 liters. After infusion of this product for 30 minutes, the blood drug concentration was 75% of the maximum blood drug concentration, and decreased to 14% after 6 hours. After a single dose of 500ml hydroxyethyl starch, the plasma concentration almost returned to the baseline level after 24 hours.
After a single administration of 500 ml, the plasma clearance rate of the drug was 3 1.4 ml/min, AUC was 1.4 mg/ml× hour, t 1/2α was 1.4 hour, and t1/. 46646
Pharmacokinetics of this product was studied in patients with mild to severe renal insufficiency. Subjects took 500 ml of this product at a time. The results showed that AUC of the drug increased moderately, and its clearance rate in muscle and liver was CLCR.
Subjects' research showed that there was no obvious accumulation of drugs in plasma when 500 ml 10% hydroxyethyl starch 130/0.4 solution was given daily for 10 days.
In the rat model test, 18 days was given at the weight of 0.7g/kg every day, and the drug content in the tissues was detected on the 52nd day after the last administration. The results showed that only 0.6% of the given dose was stored in tissues.
There is no study on the effect of dialysis therapy on pharmacokinetics of this product.
Hydroxyethyl starch: Really? No?
Author: Li Yan compiled Source: China Medical Tribune Date: 20 13-02-2 1.
Hydroxyethyl starch has been widely used in liquid resuscitation since it was listed in the 1960s. However, its efficacy and safety have been controversial. British Medical Journal (BMJ) and Journal of American Medical Association (JAMA) published two articles, which systematically reviewed and meta-analyzed the published research on hydroxyethyl starch. Here are two articles and a summary of JAMA release in the same period.
He can't bring benefits to septicemia patients.
Danish and Swiss scholars searched the evidence-based medicine library, MEDLINE and other databases, and selected randomized controlled clinical trials (RCT) published before September 20 130/0.38-0.45 to compare the efficacy and safety of crystalloid fluid or human albumin in fluid resuscitation of sepsis patients, and finally included 9 studies (involving 3456 patients) for analysis. The results showed that fluid resuscitation with HES 130/0.38-0.45 increased renal replacement therapy (RR = 1.36), acute renal failure (RR= 1. 18) and red blood cell transfusion (RR =
Risk of acute renal failure and death in patients with severe HES
Canadian scholars searched MEDLINE, EMBASE and other databases, selected 38 items of RCT * * * published before 20 12 and 10, and compared the use of HES and other resuscitation fluids (including crystalloid fluid, albumin and gel) in critically ill patients. The results showed that compared with other resuscitation fluids, hydroxyethyl starch could not reduce the mortality of patients (RR = 1.07). After excluding the seven studies conducted by Boldt (with scientific violations), HES significantly increased the mortality (RR= 1.09) and the risk of acute renal failure (RR= 1.27), and increased the use of renal replacement therapy (RR= 1.32). This paper was published in Journal of American Medical Association on February 20th [JAMA 2013,309 (7): 678].
Parallel review
Application of hydroxyethyl starch in liquid resuscitation: the disadvantages outweigh the advantages.
Antonelli and Sandroni of Italian Catholic sacred heart university.
This meta-analysis published in JAMA raises some questions worth discussing.
⑴ This result is inconsistent with the research results published in Cochrane systematic review database 20 12. The latter did not show that HES caused an increase in mortality, and whether Boldt was excluded had no effect on the results. Of course, this analysis only compares HES and crystal solution, and only two Boldt studies are included (the mortality rate is zero); However, this study includes 7 Boldt studies (different from the above two), and the control group reported 84 deaths, which will affect the overall results. In addition, this study includes three studies published on 20 12, among which 6S study is the first report that the use of HES significantly increases mortality, with a large sample size.
⑵ People tried to reduce the nephrotoxicity of HES by reducing its molecular weight and hydroxyethyl degree. However, compared with ringer's lactate solution, it is still more likely to cause renal tubular injury. The subgroup analysis of this study also confirmed this point.
⑶ This study emphasizes the seriousness of scientific violations in patient safety assessment. 20 1 1, 14 The editors-in-chief of medical journals issued a joint statement, announcing the results of the ethical review of the Boldt incident and the clinical trial conducted by the German Rheinland-falk National Medical Association (LAK-RLP). Among them, 80 studies are considered to be inconsistent with ethical standards or scientific violations.
This study confirmed the nephrotoxicity of HES and was the first meta-analysis to prove that acute fluid resuscitation with HES increased mortality. However, due to the variety of comparative liquids, there is no direct evidence for the long-standing dispute between colloidal and crystalline liquids. In the future, high-quality RCT should be carried out to evaluate the safety and effectiveness of HES.
Renal injury caused by hydroxyethyl starch exposure in European and American academic circles
Hydroxyethyl starch is a commonly used drug widely used in intensive care and anesthesiology for more than 50 years, which is accused of "causing renal function damage". The top three clinical medical journals in the world (JAMA Journal of American Medical Association, BMJ British Medical Journal, NEJM New England Journal of Medicine) have published adverse clinical research results. The source of this incident is that JoachimBoldt, an advocate of hydroxyethyl starch and a German professor, forged his paper. After the scandal broke out, the European and American intensive care societies successively issued statements saying that they were not recommended. However, according to the survey of National Business Daily, hydroxyethyl starch is still the best-selling drug in China, and its sales volume is increasing year by year. The conservative estimate in the industry has exceeded 654.38+0.5 billion yuan. Due to the shortage of blood and the increase of market sales, many domestic enterprises actively develop hydroxyethyl starch products and market development, including Kelun Pharmaceutical and China Resources Shuanghe, a big infusion giant. Regarding the side effects of the product, Kelun Pharmaceutical told the National Business Daily that it would pay close attention to the results of clinical research. As of press time, China Resources Shuanghe has not yet given a reply. Advocates' paper fraud triggered a ban in Europe and America/Recently, the top international medical magazine BMJ published an article about Yue Kaim? Bert's article, entitled "Bert the Great Forger". The article said, Yue Kaim? Burt's more than 90 clinical studies on hydroxyethyl starch are all behind closed doors. Hydroxyethyl starch is a blood volume dilator, which is mainly used for the treatment of hemorrhagic, traumatic, infectious and toxic shock in clinic. However, hydroxyethyl starch has been controversial because of its effectiveness and safety since it was listed in the 1960s. Yue Kaim? Bert became a key figure in turning the market around. Yue Kaim? Bert works in the Medical College of ludwigshafen University and is an expert in intravenous drugs. He published many papers in major European medical journals, demonstrating the effectiveness and safety of hydroxyethyl starch. Based on his research results, hydroxyethyl starch has been included in the medical guidelines of many European countries and has become a commonly used drug in clinic. Lies need to accumulate. In 2009, Yue Kaim? Bert's paper published in AnesthesiaandAnalgesia was exposed because the data was too perfect, and readers kept writing to question it. Yue Kaim? Burt's indifference led the editor-in-chief of the magazine to finally investigate this. From June 20 10 to June 20 10, the results of the investigation were surprising: this so-called clinical research was not approved by the ethics Committee, and even the drug suppliers needed for clinical trials were not supplied for many years. Subsequent investigations have proved step by step that Yue Kaim? More than 90 papers by Bert are fabricated products. Therefore, the safety and effectiveness of hydroxyethyl starch have been reconsidered. The top three clinical medical journals in the world have made unfavorable statements about hydroxyethyl starch: in terms of effectiveness, hydroxyethyl starch is not higher than similar products, but it will significantly increase the risk of kidney injury. The effectiveness is not high, there are many side effects, the price is 10 times that of similar products, and the cost performance is low, which leads to the decision not to recommend or even oppose the use of intensive care society in Europe and America. State Food and Drug Administration: Not concerned at present/According to the reporter of National Business Daily, hydroxyethyl starch is a commonly used drug in intensive care and anesthesiology departments in China. "Europe is the birthplace of hydroxyethyl starch. I used it a lot before, but it was rarely used after the scandal broke out, while the United States has been using it very little. " A person from the Institute of Critical Care Medicine of the Chinese Medical Association told the National Business Daily that many people in the Institute of Critical Care Medicine have reached a * * * understanding: clinical use with caution. However, what worries these people is that many doctors in China, including anesthesiologists and surgeons, are still ignorant of the adverse reactions of hydroxyethyl starch and the latest evidence. Expose Yue Kaim on Lilac Garden, the largest doctor's professional website in China. Bert's fraud and strong opposition from European and American countries called for doctors to use it cautiously, which caused quite a controversy after it was published in anesthesiology department. Some doctors said that "this medicine should be thrown directly into the trash can." There are also many anesthesiologists who are puzzled, saying that this drug is a common drug and has been instilled with many advantages on the first day of clinical anesthesia. Some doctors also said that the training a few days ago said how good this medicine is. Yesterday, the reporter consulted the State Food and Drug Administration as an anesthesiologist and said that they were not concerned about this drug. When the reporter tried to know the information of adverse reactions of hydroxyethyl starch as an ordinary citizen, he was told by the relevant regulatory authorities that the information of adverse reactions was only used as a reference for drug evaluation and was not made public. However, according to the official website of the US Food and Drug Administration, in the Information Bulletin of Adverse Drug Reactions in 2005, the then State Administration of Pharmaceutical Products had issued a notice on renal function damage caused by hydroxyethyl starch 40 and sodium chloride injection 20. 1988 to March 2005, there were "706 generation plasma", hydroxyethyl starch 40 sodium chloride and hydroxyethyl starch 20 sodium chloride injection in the case report database of the National Adverse Drug Reaction Monitoring Center. At that time, the State Administration of Pharmaceutical Products concluded that hydroxyethyl starch 40,20 sodium chloride injection could cause kidney injury, and medical personnel should strictly control the indications and avoid long-term large-dose and large-dose use. Industry: Products enter China or are suspected of commercial bribery/A person from the Institute of Critical Care Medicine of Chinese Medical Association said that the scandal did not have much impact on sales in China. It is understood that the sales of hydroxyethyl starch reached 400 million yuan in 2004, and now the most conservative estimate is 65.438+0.5 billion yuan. The reporter of National Business Daily found that in 2004, at the International Academic Progress Forum on Clinical Transfusion Substitution held in Juska, Fei Sen, Yue Kaim? Bert appeared as an expert to explain the benefits of Hess (hydroxyethyl starch). Hess is the trade name of hydroxyethyl starch produced by Juska Bi Company in Fei Sen, which occupies the largest share in the previous generation plasma market at home and abroad. According to industry insiders, it is not recommended internationally, but used much more in China, and commercial bribery may have played a role. The poster of a net post claimed to be an anesthesiologist in a hospital in Shenzhen, pointing out that a deputy director of the department who had served for 7 years received high kickbacks to collect money, involving tens of millions of yuan. In his list of bribery, Fei Sen Juska looms large. After the incident was exposed by the media, the hospital involved quickly launched an investigation. The Shenzhen Municipal Commission for Discipline Inspection has also received a report letter before, and is preparing to conduct an investigation, saying that its violations are true, but the specific amount has yet to be verified. Juska Company of Fei Sen did not respond to the question of whether it knew or whether the bribe was true. Kelun Pharmaceutical: Clinical reaction will be closely followed. With the increasing shortage of blood and its products, there are still many domestic manufacturers interested in hydroxyethyl starch, including domestic infusion giants China Resources Shuanghe and Kelun Pharmaceutical. In the semi-annual report of China Resources Shuanghe in 2009, hydroxyethyl starch (Yingyuan) was listed as a key product. Lianxun Securities said in the published research report that hydroxyethyl starch was also listed as the key variety of China Resources Shuanghe non-alkaline infusion. The research report shows that in 20 1 1 year, therapeutic infusion accounts for 20% of the company's infusion income, and the sales volume has rapidly increased from 25 million bottles in 201year to 52 million bottles in 201year, with a year-on-year increase of/kloc-0. Kelun Pharmaceutical has also invested a lot of energy in hydroxyethyl starch, and its sales volume has been quite high. Kelun Pharmaceutical said in the 20 12 annual report that its other product, hydroxyethyl starch sodium lactate Ringer injection, has been industrialized and has been approved by the National Development and Reform Commission for the development of generic drugs. As of press time, China Resources Shuanghe has not given a reply on whether it knows the side effects of the product and whether it has been verified by clinical trials. The reply from Kelun Pharmaceutical to the National Business Daily reporter shows that for Yue Kaim? Kelun Pharmaceutical is well aware of Berber's fraud and the opposition of foreign academic circles to hydroxyethyl starch. In addition, Kelun Pharmaceutical also admitted that there are indeed many problems in the study of hydroxyethyl starch abroad, especially the side effects on renal function damage. In this regard, the company will closely follow the clinical reaction of the drug. However, Kelun Pharmaceutical believes that the conclusions of authoritative foreign magazines and critical care societies are overkill, and the product has not been ordered to be recalled. At the same time, Lin Hongyuan, a professor of critical care medicine in PLA General Hospital, also questioned the foreign conclusions. Domestic Ruijin Hospital believes that this product still has certain advantages, and many domestic clinicians still support compatibility, so they still hold a positive attitude towards the product.
Clinical application of hydroxyethyl starch in first aid
The emergency department of Pingdu People's Hospital of Shandong Province and the Department of Orthopaedics of Pingdu People's Hospital of Shandong Province published papers to explore the clinical effect of hydroxyethyl starch 130/0.4 sodium chloride injection resuscitation method on early hemorrhagic shock. It is pointed out that the resuscitation method of hydroxyethyl starch 130/0.4 sodium chloride injection can increase the effective circulating blood volume, improve the perfusion of tissues and organs and reduce the mortality rate. This article was published in China Journal of Physician Training, Volume 35, No.24, 20 12.
52 patients with early hemorrhagic shock were randomly divided into compound sodium chloride injection group (control group) and hydroxyethyl starch 130/0.4 sodium chloride injection group (treatment group), with 26 cases in each group. The therapeutic effect, average arterial pressure, respiratory rate, heart rate, blood sodium, blood chlorine and prothrombin time of the two groups were observed and compared.
The results showed that the cure rates of the treatment group and the control group were 84.6%(22/26) and 38.5%( 10/26) respectively, and the mortality rates were 15.4%(4/26) and 610.5% (/kloc-) respectively. 0.05)。 The average arterial pressure, heart rate and respiratory frequency in the treatment group 60 minutes after treatment were (91.5 8.6) mmhg (1mmhg = 0.133 kpa) and (78.5±7.9)mmHg and (81.