2 English reference benzylpenicillin
3 Overview Benzylpenicillin is an antibiotic produced by Penicillium, Aspergillus and other fungi. Benzpenicillin is the first antibiotic that can treat human diseases. 1929, British bacteriologist Fleming obtained benzylpenicillin from Penicillium punctatum for the first time. Because of the different side chains in chemical structure, there are many kinds. Penicillin can be synthesized artificially, and some new derivatives can be prepared by modifying some of its structures by chemical methods. At present, about 30 kinds of synthetic benzylpenicillin have been put into clinical application. Penicillin produced by artificial method has low toxicity and high curative effect. For example, cyanotoxin G is only effective against Gram-positive bacteria and unstable against acid, while ampicillin is stable against acid and has a wide antibacterial spectrum.
The discovery of benzylpenicillin was a great medical achievement in the 20th century, which made an important contribution to human health and promoted the development of the whole fermentation industry. Benzpenicillin is effective against Gram-positive bacteria, such as Streptococcus, Staphylococcus, Clostridium and Bacillus. But it has no activity or low activity to gram-negative bacteria such as Escherichia coli, Vibrio and Mycobacterium. Benzpenicillin is harmless to humans and most animals. After intramuscular injection or subcutaneous injection, it can quickly spread into the blood and reach almost all tissues. Clinically, penicillin is used to treat pneumonia, abscess, bacterial meningitis, syphilis, dental and oral infections, osteomyelitis and other traumatic infections caused by penicillin-sensitive bacteria. However, benzylpenicillin can cause allergic reactions in some recipients, and in severe cases, it can cause shock or even death, so skin test must be done before application. This product is most prone to anaphylactic shock. Large doses can cause penicillin encephalopathy.
In the early 1940s, the world's first antibiotic, benzylpenicillin, came out, which provided an anti-infective drug with high efficiency and low toxicity for clinic. In recent years, the number of penicillin-resistant strains has been increasing, and new antibacterial drugs have been discovered, which has affected its clinical application to some extent. However, due to its strong bactericidal activity, good systemic distribution and low toxicity, penicillin G still has a good effect on the infection of sensitive bacteria. Benzpenicillin is still the main therapeutic drug. For patients with secondary or tertiary syphilis or severe primary syphilis, especially those with early symptoms of the central nervous system, high-dose benzylpenicillin should be used, 5 million to 20 million U per day, and the treatment effect is stable for 3 to 4 weeks. Neisseria gonorrhoeae is sensitive to benzylpenicillin, but the number of drug-resistant bacteria has increased significantly in recent years, and some drug-resistant bacteria are highly resistant. Therefore, it is necessary to decide whether to choose benzylpenicillin according to the results of drug sensitivity test, and the therapeutic dose should also be determined according to the sensitivity.
Benzylpenicillin is a national essential drug.
4 common name benzylpenicillin
5 English name benzylpenicillin
6 Another name for benzylpenicillin: sodium benzylpenicillin; Benzylpenicillin potassium; Penicillin; Benzylpenicillin g; Benzylpenicillin g; Penicillin; Benzylpenicillin
Classification of Antibacterials >: β -lactam antibiotics >:? Benzylpenicillins
British bacteriologist Fleming discovered benzylpenicillin. 1928 One day, Fleming studied staphylococci causing human fever in his humble laboratory. As the lid was not properly covered, he found that there was a layer of Penicillium attached to the agar used to cultivate bacteria. This is coming from the window of a scholar who studies Penicillium upstairs. To Fleming's surprise, Staphylococcus suddenly disappeared near Penicillium. This accidental discovery deeply attracted him, and he successfully cultivated this mold many times, which proved that penicillin could kill all staphylococci in a few hours. Fleming invented penicillin, the bane of staphylococcus.
1929, Fleming published an academic paper and reported his findings, but it was not paid attention to at that time, and the purification of penicillin was not solved.
From 65438 to 0935, biochemist Qian En and physicist Flory of Oxford University in England were very interested in Fleming's discovery. Ernst Boris Ernst boris chain is responsible for the cultivation of Penicillium and the separation, purification and strengthening of benzylpenicillin, which has improved its antibacterial power by thousands of times. Flory is responsible for the observation and experiment of animals. So far, the efficacy of benzylpenicillin has been confirmed.
Due to the discovery and mass production of benzylpenicillin, millions of patients with pneumonia, meningitis, abscess and septicemia were saved, and many wounded and sick people were rescued in time.
. The appearance of benzylpenicillin caused a sensation in the world at that time. In recognition of this contribution to the benefit of mankind, Fleming, Ernst Boris Chane and Flory won the Nobel Prize in Medicine and Physiology in 1945 * *.
9 pharmacological action benzylpenicillin has bactericidal effect on bacteria in reproductive period by interfering with the synthesis of bacterial cell wall. Benzylpenicillin sodium and potassium are not acid-resistant, and their oral absorption is poor, so they are not suitable for oral administration. It has a good antibacterial effect on streptococcus hemolyticus, streptococcus pneumoniae, staphylococcus which does not produce penicillinase, etc. It has moderate antibacterial effect on enterococcus. Neisseria gonorrhoeae, Neisseria meningitidis, Corynebacterium diphtheriae, Bacillus anthracis, Actinomyces bovis, Streptococcus moniliforme, Listeria monocytogenes, Leptospira and Treponema pallidum are sensitive to this product. This product also has certain antibacterial activity against Haemophilus influenzae and Bordetella pertussis, and other gram-negative aerobic or facultative anaerobic bacteria are less sensitive to this product. This product has good antibacterial effect on Clostridium, anaerobic bacteria of digestive streptococcus and Bacteroides melanogenesis, but it has poor antibacterial effect on Bacteroides fragilis. [ 1]
Among gram-positive cocci, Streptococcus pyogenes, Streptococcus pneumoniae and Staphylococcus aureus are highly sensitive, Streptococcus viridis is moderately sensitive and Streptococcus faecalis is moderately sensitive. Among gram-negative cocci, meningococcus is highly sensitive, Neisseria gonorrhoeae is moderately sensitive and partially resistant. Among Gram-positive bacilli, tetanus, diphtheria, anthrax and Clostridium perfringens are highly or moderately sensitive, while among Gram-negative bacilli, intestinal negative bacilli are drug-resistant, some influenza strains are moderately or low sensitive, and enzyme-producing influenza bacilli are drug-resistant. It is effective for treponema pallidum, treponema circulatory, leptospira and actinomycetes. The antibacterial mechanism of penicillin is to affect the synthesis of bacterial cell wall. According to the classical Park theory, penicillin binds to the transpeptidase necessary in the process of bacterial cell wall mucin synthesis, so that mucin cannot be synthesized and bacteria die. On the basis of Parker's theory, modern research has made great progress, mainly as follows:
1. It proves that Park's theory is basically correct, but it is not perfect. The mechanism of action of benzylpenicillin drugs is much more complicated than known.
2. It is proved that the cross-linking system has two enzyme systems, transpeptidase and carboxypeptidase. The latter can hydrolyze terminal D- alanine, but it has nothing to do with crosslinking. These two enzymes are sensitive to penicillin and can degrade and inactivate penicillin.
3. The bactericidal effect of benzylpenicillins is mainly combined with the target protein on the cell membrane, namely benzyl PBPs PBPS, which makes the bacteria unable to maintain normal morphology and normal division and reproduction, and finally cracks and dies.
4.PBPs are indispensable protein in the process of bacterial cell wall synthesis, and some PBPs are penicillin-sensitive enzymes in the process of cell wall synthesis.
5. Different PBPs have different functions. PBP 1a and PBP 1bs are related to glycopeptides, which make cells grow.
The pharmacokinetics of 10 benzylpenicillin is not acid resistant and should not be taken orally. After intramuscular injection, it reaches the peak of blood drug concentration (Cmax) within 0.5 hours, which can be widely distributed in tissues and body fluids and easily penetrate into inflammatory tissues. The concentration in pleural, abdominal and joint cavity fluid is about 50% of serum concentration. This product can penetrate the placenta, but it is difficult to penetrate the blood and cerebrospinal fluid barrier. Milk can contain a small amount of benzylpenicillin, which is difficult to penetrate into eyes, bone tissues, bloodless areas and pus cavities. The plasma protein binding rate is 45% ~ 65%, and the blood elimination half-life (t 1/2β) is about 30 minutes, which can be extended to 2.5 ~ 10 hour for patients with renal insufficiency, and is also suitable for the elderly and newborns. About 19% of this product is metabolized in the liver, mainly through renal tubules. Under the condition of normal renal function, about 75% of the dose is discharged from the kidney within 6 hours, and a small amount is discharged through the biliary tract. Hemodialysis can remove this product, peritoneal dialysis can't. [ 1]
Indications 1 1 benzylpenicillin is used for infections caused by sensitive bacteria or sensitive pathogens. Pharyngitis, tonsillitis, scarlet fever, endocarditis, erysipelas, cellulitis and puerperal fever caused by hemolytic streptococcus. Pneumonia, otitis media, meningitis and bacteremia caused by pneumococcus. Gas gangrene caused by tetanus and Clostridium. [ 1]
1. For pharyngitis, scarlet fever, cellulitis, suppurative arthritis, pneumonia, puerperal fever and septicemia caused by group A β hemolytic streptococcus, benzylpenicillin G is the first choice. For the above serious infections, intravenous drip, four times a day, each dosage1.2000 ~1.6000 u. The treatment of pharyngitis should be given at least 10 days to ensure that pathogenic bacteria are removed from the pharynx to avoid rheumatic fever in the future. Acute purulent meningitis (meningitis) and endocarditis caused by Streptococcus pyogenes should be treated by intravenous injection of large dose of penicillin G (654.38+million ~ 20 million U/ day).
2. Infection caused by other streptococci: including respiratory tract infection, acute purulent meningitis (meningitis), endocarditis and septicemia caused by group B β hemolytic streptococcus, green streptococcus and fecal streptococcus. Streptococcus pneumoniae is highly sensitive to penicillin G and can be used as the first choice for treatment.
3. Meningitis caused by meningococcus or other sensitive bacteria: Benzylpenicillin G is not easy to penetrate the normal blood-cerebrospinal fluid barrier, and the amount entering cerebrospinal fluid is small, but the permeability of meninges increases when they are injured by inflammation, and high-dose treatment is effective. The initial dose for adults is 6.5438+million ~ 20 million U/ day, which is given by intravenous drip for 4 times.
4. Gonorrhea caused by Neisseria gonorrhoeae: Neisseria gonorrhoeae is sensitive to benzylpenicillin G, but in recent years, the number of drug-resistant bacteria has increased significantly, and some drug-resistant bacteria are highly resistant. Therefore, it is necessary to decide whether to choose benzylpenicillin G according to the results of drug sensitivity test, and the therapeutic dose should also be decided according to the sensitivity.
5. Syphilis caused by Treponema pallidum: Benzpenicillin G is still the main therapeutic drug. For severe cases of secondary and tertiary syphilis or initial stage, especially those with early symptoms of central nervous system, high-dose benzylpenicillin G should be used for treatment, with a daily dose of 5 million to 20 million U, and the curative effect will be stable after 3 to 4 weeks of treatment.
6. Infection caused by Gram-positive bacilli: infection caused by tetanus, diphtheria and anthrax should be treated with benzylpenicillin G and antitoxin. Benzpenicillin is mainly used in dermatology for the following diseases: (1) syphilis. (2) gonorrhea. (3) Others such as scarlet fever, cellulitis, erysipelas, erysipelas, pyoderma, etc.
12 contraindications are prohibited for people who are allergic to penicillin or other penicillin drugs [1].
Before taking the medicine, the patient should be asked if he has any allergic history. Those who have not used penicillin for 24 hours should do intradermal sensitivity test, and those with positive test results should be banned. It is forbidden for people who are allergic to benzylpenicillin or other benzylpenicillin drugs, allergic diseases and allergic States.
13 adverse reactions penicillin common allergic reactions include severe anaphylactic shock and serum sickness type reaction, leukopenia, drug eruption, contact dermatitis and asthma attack. Toxic reactions of low-dose drugs are rare. Peripheral neuritis can occur at the site of intramuscular injection. Intrathecal injection of more than 20,000 units or large-dose intravenous drip can cause convulsion, muscle clonus and lethargy, and can also cause temporary mental disorder, which can be recovered by stopping the drug or reducing the dose. Long-term drug use may cause double infection, which may be caused by penicillin-resistant staphylococcus aureus, gram-negative bacilli or candida infection. [ 1]
1. Allergic reaction is the main adverse reaction of penicillin, including anaphylactic shock, serum sickness, rash, contact dermatitis, etc. The degree of reaction varies greatly, ranging from rash to anaphylactic shock and death. The incidence of allergic reaction was 1% ~ 10%, mostly skin rash, and the incidence of anaphylactic shock was 0.004% ~ 0.04%. It is worth noting that although the penicillin skin test is negative, there will still be allergic reactions to varying degrees and even deaths. Prevention and treatment of penicillin anaphylactic shock: ① Pay attention to asking about allergic history; ② Skin allergy test must be done, and 0.05ml of 500U/ml skin test solution should be injected intradermally, and the reaction should be observed after 20 minutes. The skin test solution should be freshly prepared and stored in the refrigerator for no more than one week. ③ Observe for 30 minutes; After injection of benzylpenicillin; ④ Penicillin antibiotics can only be injected in the case of rescuing anaphylactic shock. (2) Principles and methods of rescuing allergic shock caused by penicillin: ① Every minute counts, the patient should be rescued on the spot and lie down with his head down immediately; ② 0.5ml of 0. 1% epinephrine was injected subcutaneously into the upper arm immediately; ③ Quick preparation of intravenous infusion; (4) If the subcutaneous injection of adrenaline has no effect, repeat the subcutaneous injection once or add adrenaline to the infusion; ⑤ intravenous injection of hydrocortisone 25 ~100 mg; ⑥ In case of dyspnea or respiratory distress, aminophylline 0.25~0.5g can be injected slowly and artificial respiration can be given at the same time; ⑦ If there is angioedema and urticaria, antihistamines should be injected intramuscularly or intravenously; ⑧ Keep warm and maintain the respiratory and circulatory functions.
2. Central nervous system reaction: Large dose of benzylpenicillin (25 million U per day) can cause nervous system toxic reactions such as convulsion and coma 3 days or later after treatment, and intrathecal injection of benzylpenicillin can also cause the above reactions. High-dose penicillin injection occasionally causes abnormal mental reactions.
3. Abnormal blood reaction: Benzylpenicillin can cause unexplained neutropenia. Thrombocytopenia can also occur, but to a lesser extent. Benzylpenicillins can cause hemolytic anemia, which is an immune response caused by IgM antibody anti-benzylpenicillin red blood cell complex. A few patients may have positive reaction of Coombs test.
4. Abnormal reaction of liver and kidney function: Transient increase of liver enzymes can occur during benzylpenicillin treatment, and hemorrhagic cystitis has also been reported.
5. Benzylpenicillin can cause gastrointestinal reaction.
6. Gieher reaction: When benzylpenicillin is used to treat syphilis, Gieher reaction may occur. This is due to the large amount of endotoxin released by Treponema pallidum after being killed. Oral prednisone before medication can prevent Gieh reaction.
7. Those who have a history of penicillin allergy are prohibited. Patients with allergic diseases and allergic state are prohibited, and those with allergic history of other drugs should be used with caution.
14 Precautions [1]
(1) First, ask the allergic history in detail. People with a history of allergies are generally not suitable for skin tests.
(2) The skin test should be carried out according to the specified method (concentration is 500 units/ml, intradermal injection is 0.05 ~ 0. 1 ml).
(3) In case of anaphylactic shock, 0. 1% adrenaline 0.5 ~ 1 ml should be injected immediately. If the clinical manifestations are not improved, it should be repeated 1 time after half an hour, and other symptomatic treatments should be combined.
(4) This product is not suitable for intrathecal injection, but can be injected intramuscularly or intravenously. When the daily dose of adults exceeds 5 million units, it should be applied by intravenous injection. The speed of intravenous administration should not exceed 500,000 units per minute, and it should be rapidly dripped several times, generally every 6 hours 1 time, to avoid central nervous system reaction.
(5) Patients with a history of allergic diseases such as asthma, eczema, hay fever and urticaria should use it with caution, and those with severe renal function damage should adjust the dosage or extend the administration interval.
(6) When taking large doses of drugs, it should be considered that sodium ions or potassium ions brought in can cause hypernatremia or hyperkalemia. Benzylpenicillin sodium 1 10,000 units containing sodium ion 1.7 mmol (39 mg); Benzylpenicillin G potassium 1 10,000 units contains potassium ions 1.5mmol (65mg).
(7) The aqueous solution of this product is unstable and easy to hydrolyze, so the injection should be freshly prepared. If it must be preserved, it should be refrigerated in the refrigerator and used up within 24 hours.
15 drug interaction [1]
(1) combined with probenecid, aspirin, indomethacin and sulfonamides can reduce the excretion of benzylpenicillin drugs, increase the blood concentration of benzylpenicillin drugs and enhance the curative effect, but the toxic reaction may also increase. [ 1]
Probenecid can inhibit renal tubular secretion, so it can prolong the maintenance time of serum concentration of benzylpenicillin and has synergistic effect on benzylpenicillin.
(2) Combination with tetracycline, erythromycin, chloramphenicol and sulfonamides may reduce the antibacterial effect of this product [1].
Benzylpenicillins have antagonistic effects on tetracycline, chloramphenicol and macrolides. Because benzylpenicillin is a bactericide in the breeding period, bacterial reproduction is inhibited under the action of bacteriostatic drugs, which may make the efficacy of benzylpenicillin drugs unable to give full play.
(3) Combined with warfarin, anticoagulation can be enhanced [1].
(4) Taking contraceptives at the same time may affect the contraceptive effect [1].
(5) Benzpenicillin has synergistic effect with aminoglycoside antibiotics, but high dose of benzylpenicillin G or other semi-synthetic benzylpenicillin can reduce the activity of aminoglycosides.
16 benzylpenicillin (1) intramuscular injection Usage and dosage: ① Adults, 800,000 ~ 2 million units per day, administered 3 ~ 4 times. ② Children, 25,000 units /kg, once every 12 hours; ③ Newborn (full-term delivery): 50,000 units /kg each time, every 12 hours/kloc-0 times in the first week of birth, every 8 hours/kloc-0 times for more than one week, and every 6 hours/kloc-0 times for severe infection. [ 1]
(2) Intravenous drip: suitable for severe infection. ① Adults, 2 million ~ 20 million units per day, divided into 2 ~ 4 intravenous drip. The administration rate should not exceed 500,000 units per minute. ② Children, 500,000 ~ 200,000 units /kg daily, intravenous drip 2 ~ 4 times. ③ Newborns (full-term delivery): The dosage is the same as intramuscular injection. [ 1]
17 dosage form specifications (1) (potassium salt) sterile powder for injection: ① 0.25g (40 400,000 units); ② 0.5g (80 800,000 units). [ 1]
(2) (sodium salt) sterile powder for injection: ① 0.24g (40 400,000 units); ② 0.48g (80 800,000 sets); ③ 0.96g (6.5438+0.6 million units). [ 1]
18 benzylpenicillin is stored and dried, and stored in the dark. Don't put it in the refrigerator to prevent bottled products from absorbing moisture. [ 1]
19 benzylpenicillin poisoning benzylpenicillin (benzylpenicillin g, penicillin) is still one of the widely used antibacterial drugs in clinic, with high efficiency and low toxicity. Oral absorption is poor, the plasma protein binding rate is 45% ~ 65%, the half-life is 30min, and the renal insufficiency can be extended to 2.
.5 ~10h. Older people and newborns are also longer. It is the first choice for the treatment of group A and group B hemolytic streptococcal infections, sensitive staphylococcal infections, tetanus, diphtheria, anthrax, gas gangrene, syphilis, yaws and streptococcus viridis endocarditis. Can be intramuscular injection or intravenous drip. Common dosage: intramuscular injection of 800,000 ~ 2 million U/d, divided into 3 ~ 4 times; 2 million ~100000 u, divided into 2 ~ 4 times. This product is most prone to anaphylactic shock. Large doses can cause penicillin encephalopathy, and the dosage of penicillin should not exceed 40 million U/d [2].
Clinical manifestations of 19. 1 [3]
1. Allergic reaction ranks first among all kinds of drugs. The incidence of severe anaphylactic shock is 0.004% ~ 0.05%, and its mortality can reach 10%. Anaphylactic shock occurs very quickly, even before the needle is pulled out, it can also occur during the skin test. About 50% patients occur within 5 minutes after injection, and 90% patients occur within 20 ~ 30 minutes. Occurred several hours after injection or during continuous medication. If the penicillin skin test is negative, the possibility of penicillin allergy cannot be ruled out.
(1) The manifestations of anaphylactic shock are as follows:
1) Symptoms of airway obstruction: It is caused by laryngeal edema, bronchospasm and pulmonary edema. The patient has chest tightness, palpitation, throat obstruction, dyspnea and flushing. , accompanied by a sense of danger, dry mouth, dizziness, numbness in the face and limbs.
2) Microcirculatory disturbance: microvascular dilation leads to insufficient blood volume. The patient was pale, fidgety, chills, cold sweat, weak pulse and decreased blood pressure.
3) Central nervous system symptoms: caused by brain hypoxia. Loss of consciousness, coma, convulsion, incontinence, etc.
(2) Skin allergic reaction: itching, urticaria and various rashes. Others include nausea, vomiting, abdominal pain, diarrhea, sneezing and coughing.
(3) Other allergic manifestations: drug fever, asthma attack, allergic purpura, eosinophilia, occasional hemolytic anemia, granulocytopenia, thrombocytopenia and interstitial nephritis.
2. Penicillin encephalopathy? It is characterized by hyperreflexia, loss of consciousness, nausea, vomiting, headache, convulsion, paralysis, coma, incontinence, muscle spasm and dyspnea. The commonly used dose of benzylpenicillin is not easy to penetrate the blood cerebrospinal fluid barrier. When the central nervous system is infected, the permeability of blood cerebrospinal fluid barrier increases, and penicillin entering brain tissue can increase several times. When the concentration of cerebrospinal fluid exceeds 8 ~ 12U/ml; When the renal function is poor, the half-life of penicillin is prolonged, accumulated and the blood concentration is increased; The dose of benzylpenicillin exceeds 25 million U per day, which can cause encephalopathy. Intrathecal injection of more than 20 thousand U can also cause muscle spasm, convulsion and coma
3. Hershey reaction? Mainly seen in penicillin treatment of syphilis. If a large dose is used at the beginning, the patient will suddenly have fever, chills, headache, joint pain and other reactions within 2 ~12 hours after the first injection.
4. Peripheral neuritis? Peripheral neuritis can occur at the injection site.
5. electrolyte and acid-base balance disorder? Hyperkalemia can occur when a large amount of penicillin potassium salt is injected intravenously; Large doses of penicillin sodium salt, especially in patients with renal insufficiency or cardiac insufficiency, can cause hypernatremia and acute cardiac insufficiency, and a few patients are accompanied by hypokalemia and metabolic alkalosis.
19.2 the treatment points of penicillin poisoning are [4]:
1. Once allergic reaction occurs, stop using benzylpenicillin immediately, and you can heal yourself without medication. Serious cases should be treated with drugs.
(1) vitamin C 1 ~ 2g, 5% glucose 500 ~ 1000ml, intravenous drip of l/d; 10% calcium gluconate 10ml intravenous injection, l/d
(2) Application of antihistamines; Diphenhydramine 25 ~ 50mg, 3 ~ 4 times /d, orally; Dechlorazine 25mg, 3 times a day, orally; Astemizole 10mg, l/d, oral; Adrenal cortical hormone can be used when necessary.
2. Anaphylactic shock occurs
(1) Stop taking the medicine immediately. Let the patient lie flat, keep warm and take oxygen.
(2) Immediately inject 0.5 mg of adrenaline subcutaneously. If the symptoms are not relieved, inject/kloc-0 every 20 ~ 30 min until the symptoms are relieved.
(3) At the same time, intravenous injection of dexamethasone 5mg or hydrocortisone 200 ~ 300 mg plus 5% ~ 10% glucose 200 ~ 300 ml, intravenous drip.
(4) Application of antihistamines.
(5) In order to expand the blood volume, 10% low molecular dextran 100 ~ 250 ml can be given intravenously.
(6) If the blood pressure does not rise after the above treatment, vasoactive drugs and anti-shock treatment can be given.
(7) Symptomatic support therapy. If the heartbeat stops, perform cardiac resuscitation; Patients with respiratory failure were given oxygen inhalation and artificial respiration; Patients with laryngeal edema should do tracheotomy in time.
3. When penicillin encephalopathy occurs, penicillin should be stopped, and the symptoms can quickly subside after stopping the drug. At the same time, symptomatic support treatment was given, but the effect of anticonvulsant treatment was not good.
4. Hemodialysis can remove penicillin from blood, but peritoneal dialysis is ineffective.
5. Correct electrolyte disorder and acid-base imbalance in time.