1.

Lactulose
Drug Nomenclature
Date of monograph revision: 03-Oct-1996; 05-Mar-1998; 09-Aug-2000; 18-Oct-2001; 10-May-2004; 20-Jul-2006; 17-May-2007; 28-Jul-2008; (last modified: 29-Jul-2008) Synonyms: Lactulosa; Lactulosum; Laktulioz; Laktuloosi; Laktulos; Laktulosa; Laktulz; Laktloz BAN: Lactulose USAN: Lactulose INN: Lactulose [rINN (en)] INN: Lactulosa [rINN (es)] INN: Lactulose [rINN (fr)] INN: Lactulosum [rINN (la)] INN: [rINN (ru)] Chemical name: 4-O--D-Galactopyranosyl-D-fructose Molecular formula: C12H22O11 =342.3 CAS: 4618-18-2 ATC code: A06AD11; QA06AD11 (veterinary)

Chemical Structure of Lactulose Pharmacopoeias: In Eur. (see ) and Jpn. Chin. only contains specifications for a solution. US only

contains specifications for a solution and a concentrated liquid. Ph. Eur. 6.2 (Lactulose). A white or almost white, crystalline powder. Freely soluble in water; sparingly soluble in methyl alcohol; practically insoluble in toluene.

Ph. Eur. 6.2 (Lactulose, Liquid; Lactulose Solution BP 2008). An aqueous solution of lactulose. It contains not less than 62.0% w/v of lactulose; it may contain lesser amounts of other sugars including lactose, epilactose, galactose, tagatose, and fructose. It may contain a suitable antimicrobial preservative. It is a clear, colourless or pale brownishyellow, viscous liquid. Miscible with water. It may be a supersaturated solution or may contain crystals that disappear on heating. USP 31 (Lactulose Concentrate). A colourless to amber syrupy liquid that may exhibit some precipitation and darkening on standing. Miscible with water. Store in airtight containers preferably at a temperature between 2 degrees and 30 degrees.

Adverse Effects
Lactulose may cause abdominal discomfort associated with flatulence or cramps. Nausea and vomiting have occasionally been reported after high doses. Some consider the taste to be unpleasant; this can be minimised by dilution in water, fruit juice, or milk, or by mixing the dose with food. Prolonged use or excessive dosage may result in diarrhoea with excessive loss of water and electrolytes, particularly potassium. Hypernatraemia has been reported.

Lactic acidosis
Severe lactic acidosis developed in a patient with adynamic ileus who was being given lactulose for hepatic encephalopathy.1
1. 1. Mann NS, et al. Lactulose and severe lactic acidosis. Ann Intern Med 1985; 103: 637. PubMed

Precautions
Lactulose should not be given to patients with galactosaemia or intestinal obstruction. It should not be used in patients on a low galactose diet and care should be taken in patients with lactose intolerance or in diabetic patients because of the presence of some free galactose and lactose.

Pharmacokinetics

Taken orally, lactulose passes essentially unchanged into the large intestine where it is metabolised by saccharolytic bacteria with the formation of simple organic acids, mainly lactic acid and small amounts of acetic and formic acids. The small amount of absorbed lactulose is subsequently excreted unchanged in the urine.

Uses and Administration

Lactulose is a synthetic disaccharide osmotic laxative () used in the treatment of constipation () and in hepatic encephalopathy (). Lactulose is broken down by colonic bacteria mainly into lactic acid. This exerts a local osmotic effect in the colon resulting in increased faecal bulk and stimulation of peristalsis. It may take up to 48 hours before an effect is obtained. When larger doses are given for hepatic encephalopathy the pH in the colon is reduced significantly and the absorption of ammonium ions and other toxic nitrogenous compounds is decreased, leading to a fall in blood-ammonia concentration and an improvement in mental function. Lactulose is usually given orally as a solution containing about 3.35 g of lactulose per 5 mL, with other sugars such as galactose and lactose; an oral powder formulation is also available in some countries. In the treatment of constipation, the usual initial dose is 10 to 20 g (15 to 30 mL) given daily in a single dose or in 2 divided doses; doses up to 45 mL daily of the solution (or up to 40 g of the reconstituted oral powder formulation) have been given. The dose is gradually adjusted according to the patient's needs. For doses in children, see. In hepatic encephalopathy, an oral dose of 60 to 100 g (90 to 150 mL) is given daily in 3 divided doses. The dose is subsequently adjusted to produce 2 or 3 soft stools each day. Lactulose solution 200 g (300 mL) mixed with 700 mL of water or sodium chloride 0.9% has been used as a retention enema; the enema is retained for 30 to 60 minutes, repeated every 4 to 6 hours until the patient is able to take oral medication. References. 1. 1. Clausen MR, Mortensen PB. Lactulose, disaccharides and colonic flora: clinical
consequences. Drugs 1997; 53: 93042. PubMed

2. 2. Schumann C. Medical, nutritional and technological properties of lactulose: an update. Eur J Nutr 2002; 41 (suppl): I17I25. PubMed

Administration in children
In the UK, children may be given the following oral doses of lactulose 3.35 g per 5 mL solution for constipation; doses may be adjusted according to response: 1 month to 1 year: 2.5 mL twice daily 1 to 5 years: 5 mL twice daily 5 to 10 years: 10 mL twice daily 10 to 18 years: 15 mL twice daily

Diagnosis and testing

THE SUGAR ABSORPTION TEST.

In healthy individuals lactulose is largely unabsorbed

from the gastrointestinal tract, but in, for example, coeliac disease there is increased permeability to disaccharides such as lactulose and a paradoxical decrease in the absorption of monosaccharides. This led to the development of the differential sugar absorption test in which 2 sugars are given simultaneously by mouth and the urinary recovery of each is determined; mannitol is commonly used as the monosaccharide component and lactulose as the disaccharide. Alternatives include mannitol plus cellobiose and rhamnose plus lactulose. This absorption test is useful in the investigation of intestinal disease.1 The lack of a standardised test solution has hampered comparison of test results. Although hyperosmolar solutions are better at determining intestinal damage,2 some have preferred to use low osmolar solutions because of the risk of inducing osmotic diarrhoea, especially in children. A study found the sugar absorption test to be strongly predictive of an organic cause of chronic diarrhoea; it may be useful in improving the selection of patients who need further evaluation.3

THE LACTOSE BREATH TEST

(hydrogen breath test). Lactulose is converted by bacteria in

the large bowel to short chain fatty acids with the production of small quantities of hydrogen gas. The hydrogen is rapidly absorbed and is exhaled in the breath and measurement of its production is used to measure orocaecal transit time and carbohydrate malabsorption. However, even small doses of lactulose shortens transit time, which may limit the value of this test.4 The test is also diagnostic for bacterial overgrowth in the small intestine, which is increased in irritable bowel syndrome. Although hydrogen is produced in most subjects, methane is also produced in up to 50% of healthy subjects, and data suggest there may be clinical implications to different gas profiles. A study found that the presence of methane was associated with constipation, and with constipation-predominant irritable bowel syndrome. Methane production was infrequent in diarrhoea-predominant irritable bowel syndrome and virtually absent in inflammatory bowel disease. Diarrhoea and inflammatory bowel disease were associated with hydrogen production. Whether the type of bacterial flora causally determines symptoms is as yet unknown

2. Albumin
Drug Nomenclature
Date of monograph revision: 22-Sep-1997; 01-May-1998; 14-Sep-1999; 28-Nov-2001; 24-Jun-2004; 08-Nov-2004; 25-Nov-2005; 27-Jun-2006; 10-Sep-2008 Synonyms: Albmin; Albmina; Albumine; Albuminum ATC code: B05AA01; QB05AA01 (veterinary); QV08DA01 (veterinary) (microspheres of human albumin) NOTE: Use in Sport. Albumin may be restricted in certain sports (see ) and competitors should check with the appropriate sports authorities. Pharmacopoeias: Many pharmacopoeias have monographs, including Eur. (see ) and US.

Ph. Eur. 6.2 (Human Albumin Solution; Albumini Humani Solutio). An aqueous solution of protein obtained from the plasma of healthy donors; the plasma is tested for the absence of hepatitis B surface antigen and antibodies against HIV-1 and HIV-2 and hepatitis C virus. It is prepared as a concentrated solution containing 15 to 25% of total protein or as an isotonic solution containing 3.5 to 5% of total protein; not less than 95% of the total protein is albumin. A suitable stabiliser, such as sodium octanoate or Nacetyltryptophan or a combination of the two, may be added but no antimicrobial preservative is added. It contains not more than 160 mmol of sodium per litre and not more than 200 micrograms of aluminium per litre. The solution is sterilised by filtration and distributed aseptically into containers which are sealed to prevent contamination and maintained at 59 degrees to 61 degrees for not less than 10 hours. Finally, the containers are incubated for not less than 14 days at 30 degrees to 32 degrees or for not less than 4 weeks at 20 degrees to 25 degrees and examined visually for signs of microbial contamination. It should be stored in a colourless glass container and protected from light. A clear, almost colourless, yellow, amber, or green slightly viscous liquid. A solution in sodium chloride 0.9% containing 1% protein has a pH of 6.7 to 7.3. The BP 2008 gives Albumin and Human Albumin as approved synonyms. USP 31 (Albumin Human). A sterile, nonpyrogenic, preparation of serum albumin obtained by fractionating material (blood, plasma, serum, or placentas) from healthy human donors, the source material being tested for the absence of hepatitis B surface antigen. It is made by a process that yields a product that is safe for intravenous use. It contains 4, 5, 20, or 25% of serum albumin and not less than 96% of the total protein is albumin. It may contain sodium acetyltryptophanate with or without sodium caprylate as a stabilising agent; it contains no added antimicrobial agent. It contains 130 to 160 mmol of sodium per litre. It is a practically odourless, moderately viscous, clear, brownish fluid. It should be stored in airtight containers.

Adverse Effects and Precautions

Adverse reactions to albumin infusion occur rarely and include nausea and vomiting, increased salivation, flushing, urticaria, hypotension, tachycardia, and febrile reactions.

These effects usually respond to slowing or stopping the infusion. Allergic reactions, including severe anaphylactic shock, are possible. Rapid increases in circulatory volume can cause vascular overload, hypertension, haemodilution, and pulmonary oedema. Solutions containing albumin 20 or 25% are hyperosmotic and draw fluid from the extravascular compartment. Infusion of albumin solutions is contra-indicated in patients with severe anaemia or heart failure. They should be given with caution to patients with hypertension or low cardiac reserve. Dehydrated patients may require additional fluids. Injured or postoperative patients should be observed carefully when given albumin as the rise in blood pressure may result in bleeding from previously undetected sites. Human albumin preparations carry a risk of viral transmission. Manufacturing processes, including heating to about 60 degrees, have reduced the risk of transmitting some viral infections.

Aluminium toxicity
Albumin solutions may contain appreciable amounts of aluminium. Marked increases in plasma-aluminium concentrations have been demonstrated in patients receiving large volumes by infusion and accumulation of aluminium may occur in patients with renal impairment.1-3 In the UK albumin solutions with an aluminium content of less than 200 micrograms/litre are available for use in premature infants and patients undergoing dialysis. 1. 1. Milliner DS, et al. Inadvertent aluminum administration during plasma exchange due
to aluminum contamination of albumin-replacement solutions. N Engl J Med 1985; 312: 1657. PubMed

2. 2. Maher ER, et al. Accumulation of aluminium in chronic renal failure due to

administration of albumin replacement solutions. BMJ 1986; 292: 306. PubMed 3. 3. Maharaj D, et al. Aluminium bone disease in patients receiving plasma exchange with contaminated albumin. BMJ 1987; 295: 6936. PubMed

Critically ill patients

Volume expansion with albumin (a colloid) has been widely used in critically ill patients, although its use had never been formally tested in large controlled studies. A systematic review based on available studies up to March 1998 (relatively small, old trials that recorded only a small number of deaths) suggested that albumin was of no benefit in critically ill patients with hypovolaemia, burns, or hypoalbuminaemia, and that it might be linked to increased mortality.1 The authors of the review stressed that these results should be treated with caution but nevertheless called for an urgent reconsideration of the use of albumin in critically ill patients. The review was severely criticised2 and while it was recognised that albumin had probably been overused in the past it was considered that more studies were required to define the effect of albumin on mortality.3-5 Another review6 found that the use of albumin did not significantly affect mortality; this meta-analysis had broader criteria and included studies that were considered to be relevant but that had been excluded by the other review. In response to this debate, albumin 4% was compared with sodium chloride 0.9% for resuscitation in a study of 6997 hypovolaemic patients in intensive care (the SAFE study).7 This large, randomised, double-blind study found equivalent rates of death from any cause during the 28-day study period. Survival-time during the 28 days, length of stay in the intensive care unit and in hospital, time on mechanical inhalation or renal replacement therapy, and development of organ failure were also similar. Although these two fluids seem clinically equivalent in a heterogeneous population of patients in intensive care, further study of selected groups, such as those with trauma or severe sepsis, is required. An update to the original 1998 review included the results of SAFE. The authors maintained that patients with burns (a group excluded from the large trial) or hypoproteinaemia might still be at risk of increased mortality, and although no longer suggesting a generally increased risk, concluded that there was no evidence that albumin reduced mortality in patients with hypovolaemia. Whether highly selected groups of critically ill patients might benefit is as yet unclear.8

Pharmacovigilance data reported to albumin suppliers over 3 years (1998 to 2000) has also been analysed.9 During this period of heightened awareness about possible adverse effects of albumin, due to the publication of the 1998 review, a total of 1.62 X 107 doses of 40 g had been distributed. Serious adverse effects possibly or probably related to albumin were found to be rare, and no death was classified as probably related to albumin use. On a broader level, debate continues about the relative merits and risks of such colloid solutions, compared with those of crystalloids such as glucose or sodium chloride solutions, in the management of hypovolaemia and shock ( ).

Dilution
If concentrated albumin solutions are to be diluted before use, a suitable solution such as sodium chloride 0.9% or glucose 5% must be used. Albumin 25% that was erroneously diluted with water to produce a hypo-osmolar albumin 5% solution has produced severe haemolysis and renal failure in patients undergoing plasmapheresis,1,2 including a fatality in one patient.3
1. 1. waterUnited States, 19941998. MMWR 1999; 48: 1579. PubMed

Transmission of infections
There has been concern that albumin preparations may carry a potential risk of transmission of viral and subviral particles, notably Creutzfeldt-Jakob disease. In 1993, Pasteur-Mrieux (one of the largest producers of blood products) withdrew all products containing albumin derived from placental blood1 due to uncertainty regarding the adequacy of screening procedures for placentas as a source. It was considered that the agent responsible for Creutzfeldt-Jakob disease might be contained in placentas from women who have been treated with growth hormone derived from cadaver pituitaries. More recently, the production of blood products (including albumin) using plasma from UK donors has been phased out due to the possible risk of transmission of new variant Creutzfeldt-Jakob disease.

1. 1. Anonymous. Placental-derived albumin preparations withdrawn. WHO Drug Inf 1994; 8: 2930.

Uses and Administration

Albumin is the major protein involved in maintaining colloid osmotic pressure in the blood. It also binds a number of endogenous and exogenous substances including bilirubin, steroid hormones, and many, mainly acidic, drugs. Albumin solutions are used for plasma volume replacement and to restore colloid osmotic pressure. They have been used in conditions such as burns, severe acute albumin loss, and acute hypovolaemic shock (). They are also used as an exchange fluid in therapeutic plasmapheresis. Concentrated albumin solutions are used in neonatal hyperbilirubinaemia associated with haemolytic disease of the newborn (). They have also been suggested for short-term management of hypoproteinaemia in hepatic disease and in diuretic-resistant patients with nephrotic syndrome but are of little value in chronic hypoproteinaemias. Albumin may be included in diagnostic preparations such as those labelled with technetium-99m () for use as radiopharmaceuticals in scanning of the heart, lung, liver, spleen, bone marrow, veins, and lymphatic system. Albumin labelled with iodine-125 () is used to measure blood and plasma volumes, blood circulation, and cardiac output. A suspension of albumin microspheres with perflutren () is available for enhancing cardiac ultrasound imaging. Recombinant forms of human albumin have been developed as excipients for vaccines and other drug products, and for the treatment of hypoalbuminaemia and hypovolaemic shock. Albumin solutions are usually available as 4.5% or 5% solutions, which are iso-osmotic with plasma, and as 20% or 25% solutions which are hyperosmotic with respect to plasma, and cause a movement of fluid from the extravascular to the intravascular compartment. These concentrated solutions may be used undiluted or may be diluted with a suitable solution, commonly sodium chloride 0.9% or glucose 5%. Adequate hydration

should be maintained and electrolytes monitored in patients receiving hyperosmotic solutions of albumin. The amount of albumin solution given will depend upon the clinical condition of the patient and the response to treatment. The following doses have been suggested: acute hypovolaemic shock: an initial dose of 25 g for adults (for example, 500 mL of a 5% solution or 100 mL of a 25% solution) and up to about 1 g/kg for children hypoproteinaemia: a maximum of 2 g/kg daily neonatal hyperbilirubinaemia: 1 g/kg before exchange transfusion The rate of infusion should be adjusted according to the indication and patient response, but in general, suggested rates of infusion are up to 5 mL/minute (5% solution) or 1 to 2 mL/minute (20% solution). In plasmapheresis the albumin infusion rate should be adjusted according to the rate of removal. Albumin solutions should not be used for parenteral nutrition. 1.Lactulose Danh mc thuc Ngy ca phin bn chuyn kho: 03-Oct-1996; 05-Mar-1998; 09-Aug-2000, 18-Oct2001, 10-May-2004; 20-Jul-2006; 17-May-2007, 28-Aug -2008; (sa i ln cui: 29Aug-2008) T ng ngha: Lactulosa; Lactulosum; Laktulioz; Laktuloosi; Laktulos; Laktulosa; Laktulz; Laktloz BAN: Lactulose USAN: Lactulose INN: Lactulose [rINN (en)] INN: Lactulosa [rINN (es)] INN: Lactulose [rINN (fr)] INN: Lactulosum [rINN (la)] INN: [rINN (ru)] Tn ha hc: 4-O--D-Galactopyranosyl-D-fructose Cng thc phn t: C12H22O11 = 342,3 CAS: 4618-18-2 ATC m: A06AD11; QA06AD11 (th y) Cu trc ha hc Lactulose Pharmacopoeias:

Trong Eur. (Xem) v JPN. Chin. ch cha cc thng s k thut cho gii php. M ch cha cc thng s k thut cho mt gii php v cht lng tp trung. Ph Eur. 6.2 (Lactulose). A, mu trng hoc gn nh trng tinh bt. T do ha tan trong nc, t tan trong ru methyl, thc t khng ha tan trong toluen. Ph Eur. 6.2 (Lactulose, lng; Lactulose Gii php BP nm 2008). Mt dung dch nc ca lactulose. N cha khng t hn 62,0% w / v ca lactulose, n c th cha mt lng t hn cc loi ng khc k c ng lactoza, epilactose, galactose, tagatose, v fructose. N c th cha mt cht bo qun ph hp vi khng sinh. N l mt mu nuvng r rng, khng mu hoc mu nht, nht cht lng. C th trn ln vi nc. N c th l mt gii php bo hoc c th cha cc tinh th bin mt vo lm nng. USP 31 (Lactulose Tp trung). Mt cht lng khng mu h phch xir c th trng by mt s lng ma v ti v ng. C th trn ln vi nc. Lu tr trong cc thng cha kn tt nhit t 2 v 30 . Hiu ng bt li Lactulose c th gy kh chu bng y hi hoc kt hp vi chut rt. Bun nn v nn c i khi c bo co sau khi dng liu cao. Mt s xem xt cc hng v c kh chu, iu ny c th c gim thiu bng cch pha long trong nc, nc tri cy, hoc sa, hoc bng cch trn vi liu vi thc phm. S dng lu di hoc liu lng qu nhiu c th gy ra tiu chy vi s mt mt qu nhiu nc v in gii, c bit l kali. Hypernatraemia c bo co. Lactic toan Nghim trng nhim axit lactic pht trin mt bnh nhn vi tt rut adynamic ngi c a ra lactulose cho gan encephalopathy.1 1. 1. NS Mann, et al. Lactulose v axt lactic nng. Ann Intern Med 1985; 103: 637. PubMed Bin php phng nga Lactulose khng nn cho bnh nhn vi galactosaemia hoc tc nghn ng rut. N khng nn c s dng bnh nhn trn mt ch n ung galactose thp v chm sc cn c thc hin bnh nhn khng dung np lactose hoc bnh nhn tiu ng v s hin din ca mt s galactose min ph v lactose. Dc ng hc Dng bng ng ung, v c bn khng thay i lactulose i vo trong rut gi, ni n c chuyn ha bi vi khun saccharolytic vi s hnh thnh cc axit hu c n gin, ch yu l acid lactic v mt lng nh axit axetic v formic. S tin nh ca lactulose hp thu c sau bi tit khng thay i trong nc tiu. S dng v Qun tr Lactulose l mt Disacarit nhun trng thm thu tng hp () c s dng trong iu tr to bn () v trong bnh no gan (). Lactulose l chia nh theo vi khun rut ch yu l thnh acid lactic. iu ny tc ng nh hng a phng thm thu trong rut dn n s lng ln phn gia tng v kch thch nhu ng. N c th mt n 48 gi trc khi c hiu lc mt l thu c. Khi liu lng ln hn c a ra cho bnh no gan pH trong rut kt s gim ng k v s hp thu ca ion amoni v cc hp cht c hi khc l gim m, dn ti s gim nng amoniac mu v ci thin chc nng tm thn. Lactulose thng c ung nh l mt dung dch cha khong 3,35 g lactulose mi 5 ml, vi cc loi ng khc nh galactose v lactose; mt cng thc bt ung cng c sn mt s nc. Trong iu tr to bn, liu ban u thng thng l 10-20 g (15 n

30 mL) cho mi ngy trong mt liu duy nht hoc chia 2 ln, liu hng ngy ln n 45 ml dung dch (hoc ln n 40 g ca ti ung bt xy dng) c a ra. liu dn dn c iu chnh theo nhu cu ca bnh nhn. i vi liu tr em, nhn thy. Trong bnh no gan, mt liu ung t 60 n 100 g (90-150 mL) dng hng ngy trong chia lm 3 ln. sau liu c iu chnh to ra 2 hoc 3 phn mm mi ngy. Lactulose gii php 200 g (300 ml) trn vi 700 ml nc hoc natri clorua 0,9% c s dng nh mt thuc x gi; thuc x c gi li cho 30 n 60 pht, lp i lp li mi 4 n 6 gi cho n khi bnh nhn c th i ung thuc. Chn on v xt nghim S hp thu ng TEST. ngi khe mnh lactulose khng c hp thu phn ln l t ng tiu ha, nhng trong, v d, bnh celiac c tng tnh thm disaccharides nh lactulose v gim mt nghch l trong s hp thu ca monosacarit. iu ny dn n s pht trin ca th nghim sai s hp thu ng trong c 2 loi ng c a ra cng mt lc bng ming v phc hi cc tit niu ca tng c xc nh; mannitol thng c s dng nh l thnh phn monosaccharide v lactulose nh Disacarit ny. La chn thay th bao gm mannitol cng cellobiose v rhamnose lactulose cng. Kim tra ny hp th rt hu ch trong vic iu tra ca rut disease.1 Vic thiu mt gii php kim tra tiu chun b cn tr so snh cc kt qu xt nghim. Mc d cc gii php hyperosmolar l tt hn vic xc nh thit hi ng rut, 2 mt s ngi thch s dng cc gii php osmolar thp v nguy c gy tiu chy thm thu, c bit l tr em. Mt nghin cu tm thy nhng th nghim hp th ng c d on mnh m ca mt nguyn nhn hu c ca bnh tiu chy mn tnh, n c th hu ch trong vic ci thin vic la chn cc bnh nhn cn tip tc evaluation.3 Lactose hi th (th hydro th nghim). Lactulose c chuyn i bi vi khun trong rut ln cc axit bo chui ngn vi vic sn xut mt lng nh kh hyr. Hydro c hp thu nhanh v th ra bng hi th v o lng sn xut ca n c s dng o thi gian qu cnh orocaecal v km hp thu carbohydrate. Tuy nhin, ngay c nh liu lactulose rt ngn thi gian qu cnh, m c th gii hn gi tr ca test.4 Xt nghim ny cng c chn on cho pht trin qu mc ca vi khun trong rut non, c tng ln trong hi chng rut kch thch. Mc d hydro c sn xut hu ht cc mn hc, kh m-tan cng c sn xut trong ln n 50% ca cc i tng khe mnh, v d liu cho thy c th c ngha lm sng cu hnh kh khc nhau. Mt nghin cu thy rng s hin din ca kh m-tan c kt hp vi to bn, v vi hi chng to bn, ch yu rut kch thch. Sn xut kh m-tan khng thng xuyn trong hi chng tiu chy chim u th rut kch thch v hu nh vng mt trong bnh vim rut. Tiu chy v bnh vim rut kt hp vi sn xut hydro. Cho d cc loi vi khun mi xc nh cc triu chng vn cha bit 2. Albumin Danh mc thuc Ngy ca phin bn chuyn kho: 22-Sep-1997; 01-May-1998; 14-Sep-1999; 28-Nov2001; 24-Jun-2004; 08-Nov-2004; 25-Nov-2005, 27-Jun -2006, 10-Sep-2008 T ng ngha: Albumin; Albmina; Albumine; Albuminum ATC m: B05AA01; QB05AA01 (th y); QV08DA01 (th y) (vi ca albumin ngi) Ch : S dng trong th thao. Albumin c th c hn ch mt s mn th thao (xem) v

i th cnh tranh nn kim tra vi cc c quan chc th thao thch hp. Pharmacopoeias: pharmacopoeias Nhiu chuyn kho, bao gm Eur. (Xem) v M. Ph Eur. 6.2 (Human Albumin gii php; Albumini Humani Solutio). Dung dch protein thu c t trong huyt tng ca cc nh ti tr lnh mnh; plasma c th nghim cho s vng mt ca khng nguyn b mt vim gan B v khng th chng li HIV-1 v HIV-2 v vim gan siu vi C. N c chun b nh mt gii php tp trung c t 15 n 25% tng s protein hoc nh l mt gii php ng trng c cha 3,5-5% ca tng s protein, khng t hn 95% ca tng s protein l albumin. Mt n nh ph hp, chng hn nh octanoate natri hoc N acetyltryptophan-hoc kt hp c hai, c th c thm vo nhng khng c cht bo qun khng khun c thm vo. N cha khng qu 160 mmol natri / lt v khng qu 200 mg nhm / lt. Gii php l kh trng bng cch lc v phn phi v trng vo container c nim phong ngn chn nhim v duy tr mc 59 n 61 khng t hn 10 gi. Cui cng, cc container c khng t hn 14 ngy 30 n 32 hoc khng t hn 4 tun 20 n 25 v kim tra trc quan v nhng du hiu ca nhim khun. N s c lu tr trong mt container knh khng mu v bo v khi nh sng. A, r rng gn nh khng mu, mu vng, h phch, hoc cht lng hi sn st mu xanh l cy. Mt gii php trong 0,9% natri clorua c cha protein 1% c pH 6,7-7,3. BP nm 2008 cho Albumin v Nhn Albumin l t ng ngha c ph duyt. USP 31 (Albumin Nhn). A, v trng nonpyrogenic, chun b cc albumin huyt thanh thu c bng vt cht ct phn on (mu, huyt tng, huyt thanh, hoc rau thai) t cc nh ti tr lnh mnh ca con ngi, vt liu ngun c th nghim cho s vng mt ca khng nguyn b mt vim gan B. N c thc hin bi mt qu trnh m sn lng mt sn phm c an ton s dng tnh mch. N bao gm 4, 5, 20, hay 25% ca albumin huyt thanh v khng t hn 96% tng s protein l albumin. N c th cha acetyltryptophanate natri c hoc khng c sodium caprylate nh mt tc nhn n nh, n khng c cha thm cht khng khun. N cha 130-160 mmol natri / lt. N l mt thc t khng mi nht va phi, r rng, cht lng mu nu. N phi c lu tr trong cc thng cha kn. Hiu ng bt li v Phng nga phn ng bt li vi albumin truyn him khi xy ra v bao gm bun nn v nn, tng tit nc bt, bng, ni m ay, h huyt p, nhp tim nhanh, v phn ng st. Cc hiu ng ny thng phn ng chm li hoc ngng truyn dch. Phn ng d ng, bao gm c sc phn v nng, l c th. Nhanh chng tng khi lng tun hon c th gy ra tnh trng qu ti mch, cao huyt p, haemodilution, v ph phi. Dung dch c cha albumin 20 hoc 25% l hyperosmotic v rt ra cht dch t khoang extravascular. Truyn cc gii php albumin l chng ch nh bnh nhn thiu mu nng hoc suy tim. H cn c cn thn cho bnh nhn c huyt p cao hay d tr tim thp. Bnh nhn mt nc c th yu cu b sung cht lng. B thng hoc bnh nhn sau phu thut cn c quan st cn thn khi dng albumin nh tng huyt p c th gy chy mu t cc trang web trc khng b pht hin. Nhn chun b albumin c nguy c ly truyn virus. quy trnh sn xut, bao gm c nhit cho khong 60 , c lm gim nguy c truyn mt s bnh nhim trng do virus. Nhm c tnh Albumin gii php c th cha mt lng ng ca nhm. nh du tng nng

trong huyt tng bng nhm c chng minh nhng bnh nhn nhn c s lng ln bng cch truyn dch v tch t ca nhm c th xy ra bnh nhn suy thn impairment.1-3 trong cc gii php albumin Vng quc Anh vi mt hm lng nhm nh hn 200 mg / lt c sn s dng tr non v bnh nhn chy thn. 1. 1. Ngi lam non DS, et al. V nhm chnh trong trao i huyt tng do nhim nhm ca cc gii php albumin-thay th. N Engl J Med 1985; 312: 165-7. PubMed 2. 2. Maher ER, et al. Tch t nhm trong suy thn mn tnh do chnh quyn cc gii php thay th albumin. BMJ 1986; 292: 306. PubMed 3. 3. Maharaj D, et al. Nhm xng bnh bnh nhn trao i vi albumin huyt tng b nhim. BMJ 1987; 295: 693-6. PubMed Bnh nhn b bnh nng Khi lng m rng vi albumin (mt dng keo) c s dng rng ri cc bnh nhn b bnh nng, mc d s dng ca n khng bao gi c chnh thc th nghim trong cc nghin cu ln c kim sot. Mt nh gi h thng da trn cc nghin cu ln n Thng Ba nm 1998 (tng i nh, c th nghim m ch ghi li mt s nh cc ca t vong) cho rng albumin l khng c li nhng bnh nhn b bnh nng vi hypovolaemia, bng, hoc hypoalbuminaemia, v rng n c th l lin kt tng mortality.1 Cc tc gi ca tng quan nhn mnh rng cc kt qu ny phi c i x mt cch thn trng nhng vn ku gi xem xt li cp bch ca vic s dng albumin bnh nhn b bnh nng. Vic xem xt b criticised2 v trong khi n c cng nhn l albumin c th c lm dng trong qu kh n c coi l nghin cu nhiu hn l cn thit xc nh tc dng ca albumin trn mortality.3-5 Mt review6 thy rng vic s dng albumin khng ng k nh hng n t l t vong, iu ny phn tch meta-tiu chun rng hn v bao gm cc nghin cu c xem l c lin quan nhng iu c loi tr bi s nh gi khc. i ph vi cuc tranh lun ny, albumin 4% c so snh vi natri clorua 0,9% hi sc trong mt nghin cu ca 6.997 bnh nhn hypovolaemic trong chm sc c bit (cc nghin cu SAFE) .7 ny ln, ngu nhin, m i nghin cu cho thy t l tng ng vi t vong bt k nguyn nhn trong thi gian hc 28 ngy. Thi gian sng st trong 28 ngy, thi gian lu tr ti cc n v chm sc tch cc v trong bnh vin, thi gian trn ng h hp c hc hoc liu php thay th thn, v pht trin suy c quan cng tng t. Mc d hai nc c v lm sng tng ng trong mt dn s khng ng nht ca bnh nhn trong chm sc c bit, nghin cu su hn ca cc nhm c la chn, chng hn nh nhng ngi c chn thng hoc nhim trng huyt nng, c yu cu. Bn cp nht ca nh gi ban u c 1998 kt qu ca SAFE. Cc tc gi cho rng, bnh nhn b bng (mt nhm b loi tr khi cc th nghim ln) hoc hypoproteinaemia vn c th c nguy c t vong tng ln, v mc d khng cn cho thy mt nguy c thng tng ln, kt lun rng khng c bng chng cho thy albumin gim t l t vong bnh nhn hypovolaemia. Cho d nhm c chn lc ca bnh nhn b bnh nghim trng c th c li vn cha unclear.8 Dc liu bo co vi albumin nh cung cp hn 3 nm (1998-2000) cng c analysed.9 Trong thi gian ny ca nhn thc cao v hiu ng c th bt li ca albumin, do vic xut bn ca vic xem xt nm 1998, tng cng l 1,62 X 107 liu g 40 c phn pht. hiu ng bt li nghim trng c th hoc c th lin quan n albumin c

tm thy l rt him, v ci cht khng c phn loi l c th lin quan n s dng albumin. Trn mt mc rng hn, cuc tranh lun tip tc v cc gi tr tng i v ri ro ca cc gii php nh keo, so vi nhng gii php crystalloids nh glucose hoc natri clorua, trong qun l ca hypovolaemia v sc (). 1. 1. Thng tch Cochrane Group Albumin phn bin. Nhn albumin quan hnh chnh bnh nhn b bnh: c h thng nh gi th nghim ngu nhin c kim sot. BMJ 1998; 317: 235-40. PubMed 2. 2. Khc nhau. Nhn albumin qun l nhng bnh nhn b bnh nng. BMJ 1998; 317: 882-6. [Th.] 3. 3. Tomlin M. Albumin s dng trong cc bnh nghim trng. Pharm J nm 1998; 261: 193. 4. 4. McClelland B. Albumin: ng nhm ln gia chng ti vi cc s kin. BMJ 1998; 317: 829-30. PubMed 5. 5. y ban v an ton ca thuc / Thuc C quan kim sot. S an ton ca albumin ngi. Vn hin ti nm 1999; 25: 11. C sn ti: trc tuyn (truy cp 08/06/06) 6. 6. MM Wilkes, Navickis RJ. Bnh nhn sng st sau khi dng albumin ngi: mt siu phn tch ngu nhin, cc th nghim kim sot. Ann Intern Med 2001; 135: 149-64. PubMed 7. 7. Cc nh iu tra nghin cu SAFE. Mt so snh ca albumin v mn cho hi sc cht lng trong chm sc c bit. N Engl J Med 2004; 350: 2247-56. PubMed 8. 8. Cc Albumin phn bin. Nhn albumin gii php cho hi sc v khi lng m rng nhng bnh nhn b bnh nng. C sn trong C s d liu Cochrane ca h thng xt; s 4. Chichester: John Wiley, 2004 (truy cp 27/10/05). PubMed 9. 9. Vincent J-L, et al. An ton ca con ngi albumin-nghim trng tc dng ph c bo co trn ton th gii trong nm 1998-2000. Br J Anaesth nm 2003; 91: 625-30. PubMed Pha long Nu gii php albumin tp trung s c pha long trc khi s dng, mt gii php ph hp nh natri clorua 0,9% hoc glucose 5% phi c s dng. Albumin 25% l sai lm pha long vi nc sn xut mt albumin hypo-osmolar 5% dung dch sn xut haemolysis nng v suy thn bnh nhn tri qua plasmapheresis, 1,2 bao gm mt t vong trong mt patient.3 1. 1. Steinmuller DR. Mt li nguy him trong cc pha long albumin l 25 phn trm. N Engl J Med 1998; 338: 1226. PubMed 2. 2. Pierce LR, et al. Tn huyt v suy thn kt hp vi s dng nc tit trng tim vo dung dch long 25% albumin ngi. Am J-Syst Pharm Y t nm 1998; 55: 1057,1062, 1070. PubMed 3. 3. Cha xc nh. Tn huyt ca con ngi lin kt vi albumin 25% pha long vi nc v trng, Hoa K, 1994-1998. MMWR nm 1999; 48: 157-9. PubMed Truyn nhim Hin c lo ngi rng cc ch phm albumin c th mang mt nguy c tim n ly truyn ca cc ht virus v subviral, c bit l bnh Creutzfeldt-Jakob. Nm 1993, Pasteur-Mrieux (mt trong nhng nh sn xut ln nht ca cc sn phm mu) rt tt c cc sn phm c cha albumin c ngun gc t nhau thai blood1 do s khng chc chn v tnh y ca th tc kim tra nhau thai nh l mt ngun. N c coi l tc

nhn chu trch nhim v Creutzfeldt-Jakob bnh c th c trong nhau thai t nhng ph n c iu tr bng hormone tng trng c ngun gc t pituitaries t thi. Gn y, vic sn xut cc sn phm mu (bao gm albumin) bng cch s dng huyt tng t cc nh ti tr: Anh b loi b v ri ro c th ly truyn bnh Creutzfeldt-Jakob mi bin th. 1. 1. Cha xc nh. cc ch phm c ngun gc t nhau thai albumin b thu hi. WHO thuc Inf nm 1994; 8: 29-30. S dng v Qun tr Albumin l protein chnh c lin quan trong vic duy tr p sut thm thu keo trong mu. N cng lin kt vi mt s cht ni sinh v ngoi sinh bao gm c bilirubin, cc hormone steroid, v nhiu loi thuc, ch yu l axit,. Albumin gii php c s dng thay th lng huyt tng v phc hi p sut thm thu keo. H c s dng trong iu kin nh bng, mt albumin nng cp tnh, v sc hypovolaemic cp tnh (). Chng cng c s dng nh l mt cht lng trao i trong plasmapheresis iu tr. cc gii php tp trung albumin c s dng trong hyperbilirubinaemia s sinh lin quan n bnh tn huyt ca tr s sinh (). H cng c xut qun l ngn hn ca hypoproteinaemia trong bnh gan, li tiu bnh nhn khng vi hi chng thn h nhng t gi tr trong hypoproteinaemias mn tnh. Albumin c th c bao gm trong cc ch phm chn on nh l nhng nhn vi Tc99m () s dng nh radiopharmaceuticals trong qut ca tim, phi, gan, l lch, ty xng, tnh mch, v h thng bch huyt. Albumin c nhn vi it-125 () c s dng o mu v huyt khi lng, lu thng mu v cung lng tim. Mt nh ch vi albumin vi perflutren () c sn tng cng hnh nh siu m tim. cc hnh thc ti t hp ca cc albumin con ngi c pht trin nh l t dc i vi vc xin v cc sn phm thuc khc, v iu tr hypoalbuminaemia v sc hypovolaemic. Albumin gii php ny thng c sn nh l 4,5% hoc 5 gii php%, l iso-thm thu vi huyt tng, v l 20% hoc 25% cc gii php l hyperosmotic i vi huyt tng, v gy ra mt s chuyn ng ca cht lng t extravascular ngn ni mch . Nhng gii php ny tp trung c th c s dng khng pha long hoc c th pha long vi mt gii php ph hp, thng NaCl 0,9% hoc glucose 5%. hydrat ha y nn c duy tr v gim st in nhng bnh nhn nhn c cc gii php hyperosmotic ca albumin. S tin ca gii php albumin c s ph thuc vo tnh trng lm sng ca bnh nhn v p ng vi iu tr. Cc liu lng sau y c xut: hypovolaemic sc cp tnh: mt liu ban u ca 25 g cho ngi ln (v d, 500 ml dung dch 5% hoc 100 ml dung dch 25%) v ln n khong 1 g / kg cho tr em hypoproteinaemia: ti a l 2 g / kg / ngy hyperbilirubinaemia s sinh: 1 g / kg trc khi truyn trao i T l tim truyn phi c iu chnh theo ch dn v tr li bnh nhn, nhng ni chung, ngh mc gi ca truyn c ln n 5 ml / (dung dch 5%) pht hoc 1-2 ml / pht (20% dung dch). Trong plasmapheresis t l albumin truyn phi c iu chnh theo t l b ra. Albumin gii php khng c s dng cho dinh dng nui.

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