Effects and mechanism of anaphylactoid reaction induced by nonapeptide activating mast cells / 中国药房

OBJECTIVE To study the effects and potential mechanism of anaphylactoid reaction induced by nonapeptide IVQKIKHCF activating mast cells. METHODS Using human mast cell line LAD2 as subject， and substance P as positive control， the activation effects of 25， 50 and 100 μmol/L IVQKIKHCF on mast cells were investigated by determining the release rate of β-aminohexosidase， histamine release， and the contents of inflammatory factors； using MrgprX2-knockdown LAD2 cells and Mas- related G protein-coupled receptor X2 （MRGPRX2） high-expression human embryonic kidney cell line HEK293 （MRGPRX2/ HEK293 cells） as subject， the correlation between the activation effect of IVQKIKHCF and MRGPRX2 was investigated by determining the release rate of β-aminohexosidase， and intracellular calcium ion concentration. RESULTS IVQKIKHCF with 25， 50， 100 μmol/L could significantly increase the release rate of β-aminohexosidase and histamine release in LAD2 cells （P＜0.05）， and promote the release of tumor necrosis factor-α， interleukin-8， macrophage inflammatory protein-1β and monocyte chemotactic protein-1 to varying degrees （P＜0.05）. After knocking down MrgprX2， the effects of 25， 50， 100 μmol/L IVQKIKHCF promoting the release of β-aminohexosidase in LAD2 cells were reversed significantly （P＜0.05）， resulting in an increase of calcium ion concentration in MRGPRX2/HEK293 cells. CONCLUSIONS Nonapeptide IVQKIKHCF can promote mast cells to release granular matter and inflammatory mediators by activating MRGPRX2 thus inducing anaphylactoid reaction.

Changes of peripheral blood tenascin-C level in children with Kawasaki disease and its clinical significance / 中华实用儿科临床杂志

Objective:To compare peripheral blood tenascin-C (TN-C) level in patients with Kawasaki disease (KD) on admission, after treatment and at recovery, and to assess the potential of TN-C as a novel predictor for coronary artery lesion.Methods:Retrospective study.Blood samples of 44 KD patients [including 21 patients with coronary artery lesions (CAL + group) and 23 patients without coronary artery lesions(CAL - group)], 39 anaphylactoid purpura patients and 36 non-infected and non-vasculitis controls in the Affiliated Hospital of North Sichuan Medical College during January 1, 2018 and November 1, 2018 were collected.TN-C level was measured by enzyme-linked immunosorbent assay.Normally distributed data were compared by the t test; otherwise, they were compared by the Mann- Whitney U test. Pearson product-moment correlation coefficient or Spearman rank correlation coefficient was used to analyze the correlation between TN-C and other laboratory indexes. Results:For KD patients, TN-C levels on admission [(32.0±13.8) μg/L] and after treatment [(33.5±11.4) μg/L] were significantly higher than that at recovery [(23.3±10.8) μg/L](all P<0.01), which was positively correlated with C-reactive protein ( r=0.317, P=0.038), and negatively correlated with sodium level ( r=-0.472, P=0.004). No significant difference in TN-C level was found between CAL + group and CAL - group [on admission: (31.7±15.4) μg/L vs.(32.3±12.5) μg/L; after treatment: (32.2±11.6) μg/L vs.(34.8±11.3) μg/L; at recovery: (22.6±7.3) μg/L vs.(24.0±13.4) μg/L; all P>0.05]. In addition, TN-C level in patients with KD [(32.0±13.8) μg/L] and anaphylactoid purpura [(37.2±18.2) μg/L] was significantly higher than that of control children [(24.0±8.05) μg/L] (all P<0.01). Conclusions:The study findings are able to prove the potential of peripheral blood TN-C as a predictor for coronary artery lesion in KD patients, nor as a maker of vascular injury.Nevertheless, it may be used as an indicator of immune response in the acute phase of KD.

Screening of Shuanghuanglian Injection allergenic ingredients based on immune fingerprint / 中国中药杂志

In this paper,immune fingerprint was used to screen the allergenic components of Shuanghuanglian Injection(SHLI) by enzyme-linked immuno sorbent assay(ELISA) combined with HPLC/MS method. ELISA-embedded anti-IgE antibody could successfully adsorb allergens in SHLI and its plasma samples containing drugs through different routes of administration,suggesting that SHLI can induce type I hypersensitivity in rats. HPLC fingerprints and MS map of SHLI and drug-containing plasma samples from different routes of administration before and after anti-IgE antibody adsorption were established. According to the similarity evaluation of HPLC fingerprints and analysis results MS map,the sensitization of traditional Chinese medicine injections can be changed by different administration methods. There were 22 kinds of components that can be adsorbed by specific anti-Ig E antibodies in Shuanghuanglian Injection and its drug-containing plasma,most of them were acids and nitrogen compounds. Based on supramolecular theory,it was inferred that these compounds came from SHLI or body,and may form supramolecular hapten,which results in immunotoxicity and allergic reaction when being used as injection instead of oral liquid. Immune fingerprint is not only used to screen out single component allergen,but also more comprehensive,sensitive and easy to operate. It can provide reference for the future research methods of allergic reaction of traditional Chinese medicine injections.

Establishment of new evaluation standards for systemic anaphylactoid reactions using mouse model / 中国中药杂志

The detection of drug-induced anaphylactoid reactions remains a global challenge,still lacking mature and reliable animal models or test methods. Therefore,the purpose of this paper is to explore and establish the test methods and evaluation standards for anaphylactoid reactions that apply to injection drugs. Based on the anaphylactoid reaction symptoms of mice induced by intravenous injection drugs C48/40 and Tween 80,a list of systemic anaphylactoid reaction symptoms in mice was sorted out and an evaluation standard of anaphylactoid reactions symptoms was established by applying symptom intensity coefficient K( that can represent these verity of anaphylactoid reaction symptoms) and its calculation formula Accordingly,histamine,tryptase,and Ig E were selected as blood indicators of anaphylactoid reactions,so that a test method combining symptoms evaluation and blood makers detection was established.This test method could be used to evaluate the characteristics of anaphylactoid reactions: coefficient K,blood histamine levels were highly and positively correlated with C48/80 and Tween 80 dose; The log value of histamine was highly and positively correlated with K; tryptase level may rise,or remain steady,or drop,possibly associated with the characteristics of the tested object and time for blood taking; and Ig E level would drop or remain steady,but it would not rise,which can be clearly distinguished from type I allergic reactions. On this basis,tiohexol,iopromide,paclitaxel,Xuesaitong Injection,Shuanghuanglian Injection and Shengmai Injection were used to investigate the applicability. The testing results showed a high degree of consistency with the actual clinical situation. The results suggest that the method of systemic anaphylaxis test in mice has high sensitivity,specificity and good consistency with clinical practice.It is suggested to be further validated and popularized.

Study on safflower yellow for injection based on cell degranulation and acute anaphylactoid model / 中国中药杂志

This paper was aimed to establish screening methods of anaphylactoid reaction caused by safflower yellow for injection based on RBL-2 H3 cell degranulation model and mice model for acute anaphylactoid reaction,and evaluate the hypersensitivity caused by safflower yellow for injection from different batches. An in vitro cell model was used to keep the cells stimulated for an hour with different batches of safflower yellow for injection as the drug group,serum-free MEM medium as negative control group and 30 mg·L-1 C48/80 as positive control group respectively. The supernatant was then absorbed,and neutral red staining technique was used to detect the effect of safflower yellow injection on the degranulation of RBL-2 H3 cells with the positive cell rate of degranulation as the indicator.An in vivo model was established to validate the experimental results,and mice model for acute anaphylactoid reaction and ELISA method were adopted to detect the plasma histamine content,and screen the hypersensitivity caused by safflower yellow for injection at the animal level by using plasma histamine content as a test index. The results of the neutral red staining experiments showed that the positive control C48/80 could cause cell degranulation,and most of the cells were deeply stained. There was significant difference in positive cell rate between different batches of safflower yellow and positive control group. In the mice model for acute anaphylactoid reaction,it was found that the positive control C48/80 significantly increased the histamine content in the plasma of mice,while the safflower yellow in each batch did not cause a significant increase in plasma histamine( P<0. 000 1). The mechanism of anaphylactoid reaction is relatively complicated. This study was mainly based on the release of histamine and other active substances by degranulation of mast cells. No significant degranulation reaction of RBL-2 H3 cells induced by safflower yellow for injection was detected,nor was the plasma histamine level significantly increased in mice from the in vitro and in vivo aspects.

Embolismo de líquido amniótico / Amniotic fluid embolism

Resumen El embolismo de líquido amniótico es una complicación seria y potencialmente mortal del embarazo, la cual es considerada imprevenible e impredecible. La mayoría de los casos ocurren durante la labor de parto, sin embargo hasta un tercio ocurren en el postparto inmediato. Su presentación es abrupta y se cree se debe a una respuesta anormal ante el paso de tejido fetal a la circulación materna, a través del sitio de inserción de la placenta. Ante la ausencia de criterios diagnósticos establecidos o pruebas de laboratorio específicas, los signos y síntomas clásicos como hipoxia, hipotensión y coagulopatía, en ausencia de otra explicación, conforman el diagnóstico clínico. Estos deben ser rápidamente identificados y tratados por parte de un equipo multidisciplinario, con el fin de reducir la morbilidad y mortalidad materna.

Abstract Amniotic fluid embolism is a serious and life-threatening complication of pregnancy, it is considered unpreventable and unpredictable, most cases occur during labor, however up to a third occur in immediate postpartum, its presentation is abrupt and is believed to be due to an abnormal response to the passage of fetal tissue to maternal circulation through the insertion site of the placenta. Due to the lack of established diagnostic criteria or specific laboratory tests, classic signs and symptoms such as hypoxia, hypotension and coagulopathy, in the absence of another explanation, make up the clinical diagnosis, these must be quickly identified and treated by a multidisciplinary team, in order to reduce maternal morbidity and mortality.

Experimental Study on Anaphylactoid Reactions of Hydroxyethyl Starch 40 Sodium Chloride Injection / 中国比较医学杂志

Objective To evaluate the sensitizations of Hydroxyethyl Starch 40 Sodium Chloride Injection . Methods Active systemic anaphylaxis ( ASA) test, internal sensitive index ' s determination and screening and Passive Cutaneous Anaphylaxis ( PCA) test are carried out .Observe the allergy safety of the samples .Results We use guinea pigs to carry on ASA test and PCA test with Hydroxyethyl Starch 40 Sodium Chloride Injection from 45 batches of 3 companies and no changes have occurred .Measuring and comparing the sensitive index of HIS ,IgG, IgM and IgE in plasma, IgM and IgE are not obvious variation;HIS and IgG positive group and negative group and sample groups are different .Conclusions It is suggestion that Hydroxyethyl Starch 40 Sodium Chloride Injection safety evaluation should include allergic reactions , HIS and IgG sensitive index monitoring in clinical application of hydroxyethyl starch .

Amniotic fluid embolism: historical perspective, pathophysiology and clinical management / Embolia de líquido amniótico: perspectiva histórica , fisiopatología y manejo clínico

Amniotic fluid embolism (hereafter, AFE) is a uniformly devastating event that is both unpredictable and unpreventable. Despite having been first described nearly 80 years ago, it remains a significant cause of maternal mortality worldwide. AFE is characterized by the triad of sudden hypoxia and hypotension, followed in most cases by coagulopathy. The diagnosis of AFE is clinical and prompt recognition and multi-disciplinary intervention essential. This paper seeks to review the history, pathophysiology, potential risk factors, strategies for identification and management, and outcomes of this unfortunate and storied obstetric emergency.

La embolia de líquido amniótico (ELA) es una ocurrencia devastadora, impredecible y no prevenible. A pesar de haber sido descrita por primera vez hace casi 80 años, todavía es causa significativa de mortalidad materna en el mundo. La ELA se caracteriza por la triada consistente en hipoxia súbita e hipotensión, seguida en la mayoría de casos por coagulopatía. El diagnóstico de la ELA es clínico, y es esencial su pronto reconocimiento y la intervención multidisciplinaria. Este artículo trata de revisar la historia, fisiopatología, factores de riesgo potenciales, estrategias para su identificación y manejo, así como los resultados de esta desafortunada y antigua emergencia obstétrica.

Pharmaceutical Intervention and Care for Anaphylactoid Purpura Patient by Clinical Pharmacist / 中国药师

Objective:To improve the effectiveness and safety of drugs and the compliance of patients with anaphylactoid purpura through the participation of clinical pharmacists in the practice of pharmaceutical treatment .Methods:In the treatment of one patient with anaphylactoid purpura , clinical pharmacists took part in the whole process and provided the individualized regimen , adverse reac-tion monitoring , relative indices monitoring and drug education after the discharge .Results:Through the participation of clinical phar-macists in the medication development , the rational use of drugs was strengthened and the treatment process was monitored .As a re-sult, the infection of the patient obtained effective control .Conclusion:The participation of clinical pharmacist in the treatment of pa-tients with anaphylactoid purpura reflects the patient-oriented pharmacy service concept , which improves the efficiency and safety of treatment.

A high content screening method for detection of anaphylactoid reaction of injection formulations / 中国中药杂志

Anaphylactoid reaction (AR) is the most common adverse reaction of injection formulations, however, there are obvious drawbacks in available methods for AR detection. A novel in vitro detection method for AR was established based on fluorescent labeling and high content screen (HCS) system in present study. With the use of RBL-2H3 cells degranulation model, positive cell count was determined with specific cellular membrane fluorescent dye FM4-64 labeling vesicle recycle, and total cells count was determined with specific nucleus fluorescent dye Hochest 3334, and then the ratio of cells degranulation after drug stimulation was calculated. In order to verify the reliability of this HCS method, positive drug Compound 48/80 was first used to confirm the consistence of HCS method with the traditional β-hexosaminidase release test and the Evans blue staining ears test in mice. The results showed high consistence between HCS method and traditional testing methods, and the HCS method showed higher sensitivity than the other two tests. Then 30 samples of Danhong injection (DHI) with clinical allergy symptoms further were used to confirm the reliability of this HCS method. The HCS results showed high consistence with the clinical report, and the HCS method had the advantage in reducing the interference by drug color. Therefore, this HCS method is reliable, sensitive, simple and high-throughput method in detection of AR, applicable for the AR evaluation of injection formulations, and can provide guidance for safety of clinical application in clinical practice.

Analysis of 27 Cases of Anaphylactoid Reactions Caused by Magnesium Isoglycyrrhizinate Injection / 中国药房

OBJECTIVE:To explore the regularity and characteristics of anaphylactoid reactions induced by Magnesium iso-glycyrrhizinate injection,and provide reference for clinical rational drug use. METHODS:27 ADR reports induced by Magnesium isoglycyrrhizinate injection from Hunan Center for ADR Monitoring from Jan. 2014 to Mar. 2015 were retrospectively analyzed. RE-SULTS:In the 27 cases,15 were male (55.56%) and 12 were female (44.44%),with percentage of 1.25∶1;ADR mainly oc-curred in patients with 41-60 years old(51.85%);involved organ/system were mainly skin and its appendages(35.85%)and sys-temic damage(26.42%),the main clinical manifestations were rash,itching,fever,chills,vomiting and dizziness;there were 7 severe ADR reports(25.92%),mainly showed chills,fever and other systemic symptoms;most ADR can be cured(40.74%)or relieved(55.56%)by related processing. CONCLUSIONS:There are no risk tips for severe allergic reactions in instruction,it is necessary to strengthen post-marketing surveillance and further improve the drug instructions to reduce the risk of severe ADR in-duced by Magnesium isoglycyrrhizinate injection.

Research on imbalances of peripheral blood Th17 cells and Treg cells in Anaphy-lactoid purpura children / 中国免疫学杂志

Objective:To evaluate the roles of imbalance between peripheral blood T helper17(Th17) cells and CD4+CD25+regulatory T(Treg) cells in the pathogenesis of Anaphylactoid purpura(AP).Methods: Peripheral blood samples were obtained from fifty-two patients with AP and thirty age-and sex-matched healthy controls.The percentage of Th17 cells and Treg cells in peripheral blood were detected with Flow cytometry.Furthermore,the serum level of IL-6,IL-17,IL-22 and IL-23 and transforming growth factor (TGF)-βand IL-10 were detected with the use of enzyme linked immunosorbent assay(ELISA).Results: In comparison with the controls,the AP children showed a higher percentage of Th17 cells and an increased serum level of IL-6,IL-17,IL-22 and IL-23(P<0.05),but the percentage of Treg cells and the serum level of TGF-βand IL-10 were significantly lower in AP group(P<0.05).Con-clusion:AP children experience a change in the percentage of peripheral blood T helper17 cells and CD4+CD25+regulatory T cells in peripheral blood.The imbalance between the Th17 cells and Treg cells in peripheral blood may contribute to the development of Ana-phylactoid purpura.

A Case Which Presented Morbidity Considered to Be Anaphylactoid Purpura after Thoracic Endovascular Aortic Repair / 日本心臓血管外科学会雑誌

We herein report a 79-year-old man who developed anaphylactoid purpura after thoracic endovascular aortic repair, which he underwent for a distal aortic arch aneurysm of saccular type. On the third postoperative day he had purpura over his lower legs and abdomen accompanied by intermittent fever. His serum C-reactive protein concentration reached a maximum of 12 mg/dl, and remained at around 4 mg/dl thereafter. A dermatologist diagnosed anaphylactoid purpura ; this gradually improved with topical steroid and the nature and dosage of the oral medication. We suspected the presence of malignancy ; however, appropriate investigations failed to identify a cause for the purpura. During 6 months of outpatient follow up he has been free of recurrence. Anaphylactoid purpura occurs most frequently in childhood, often after an upper respiratory tract infection, whereas this condition is rare in adults. Triggers for anaphylactoid purpura include surgery, infection, certain medications, chronic lung, liver, or renal failure, and malignancy. We believe that the stress of undergoing thoracic endovascular aortic repair was the trigger in this case. Anaphylactoid purpura may be complicated by arthritis, gastrointestinal involvement and renal manifestations. There were no such complications in this case.

Pseudoallergic reactions of traditional chinese medicine injections and the approaches for risk prevention and control / 中国药学杂志

Allergic hypersensitivity reactions (AHRs) are the most commonly reported adverse reactions of traditional Chinese medicine injections, mainly including skin and mucosa redness, itching, abdominal pain, chest tightness, dyspnea and nausea, blood pressure decline, with clinical symptoms, and even shock or death. In this paper, we analyzed the characteristics of clinical adverse reactions and preclinical study results of traditional Chinese medicine injections, and proposed a view of point that the main adverse reactions of traditional Chinese medicine injections are nonallergic hypersensitivity reactions (NHRs) or pseudoallergic reactions (PARs) instead of real AHRs. Because there are absolute differences in the characteristics and the pathogenesis mechanisms between PARs and AHRs, they should not be confused, otherwise, the clinical processing measures and the direction of basic research on the adverse reactions of traditional Chinese medicine injections would be misleading. This paper also discussed the approaches for risk prevention and control of PARs of traditional Chinese medicine injections.

Methodological and Applicability Study of Rat Skin Anaphylactoid Test / 中国中医药信息杂志

Objective To study the sensitivity and reliability of rat skin anaphylactoid test method, detect and evaluate the anaphylactoid reaction of traditional Chinese medecine injection. Methods The condition of rat skin anaphylactoid test was optimized by studying the influencing factors of sensitivity and reliability of test with C48/80 as a tool drug, Tween80, endotoxin, China cobra toxin, trichosanthin injection, Tanreqing injection and Xuesaitong injection were investigated. Results The best conditions of rat skin anaphylactoid test was as follows:intrademal inject the drug with insulin syringe, 50-100μL per point, immediately inject 0.5%Evans blue dye 1 mL though caudal vein, 15 min later, kill the rat by carotid artery bleeding, clip dorsal skin to do the test. With this method, Tween80, endotoxin, China cobra toxin and trichosanthin injection all can induce blue stain in rat skin. Tanreqing injection showed no blue stain at the clinical dose. Xuesaitong injection although can induce blue stain in rat skin at the clinical dose, but the results cannot exclude the interference of its pharmacological function. Conclusion The method is simple with short test cycle, less dose of test drug, high detection sensitivity and good reproducibility, but some drug can show false positive result due to its own property.

Study on Anaphylactoid Reaction Induced by Shuanghuanglian Injection / 中国中医药信息杂志

Objective To observe the anaphylactoid reactions of Shuanghuanglian injection, determine the serum histamine level of sensitized animal, and to investigate its correlation with anaphylactoid reactions.Methods The guinea pigs were randomly selected to observe the anaphylactoid reactions using Shuanghuanglian injections in the different injection speed or different doses, and the serum histamine and the serum IgE of sensitized animals were determined by ELISA. Results The anaphylactoid reactions were induced by Shuanghuanglian injections in the different conditions of injection speed and doses in guinea pigs. There were no obvious difference about the serum IgE level between Shuanghuanglian group and saline group were injected in injection speed and doses. The serum histamine level was significantly increased in Shuanghuanglian group both different conditions of injection speed and doses, and it related to doses and speed. Conclusion Shuanghuanglian injection can cause anaphylactoid reactions in guinea pigs, and the changes of serum histamine level are related to injection speed and doses of Shuanghuanglian injection.

Studies on Anaphylactoid Reactions Induced by Traditional Chinese Medicine Injections of Qingkailing and Xuesaitong / 中国中医药信息杂志

Objective To study anaphylactoid reactions induced by traditional Chinese medicine injections (TCMI) of Qingkailing (QKL) and Xuesaitong (XST) with RBL-2H3 cells;To provide some reference for improving the screening system of TCMI induced anaphylactoid reactions.Methods The IC50 induced by QKL and XST injections was determined by MTT assay. RBL-2H3 cells were stimulated with TCMI at different concentrations or with C48/80 or culture medium. Thirty minutes later, the supernatant was collected to determine the release of histamine andβ-hexosaminidase. The cell degranulation rate and the ultrastructure changes were observed. The ICR mice were given single injection of TCMI containing Evans Blue through tail vein. The number of the animal with blue ear, the total number of blue ears and the quantity of Evans Blue of extravasation were determined 30 minutes later.Results The IC50 of both QKL injection and XST injection was 12.5μL/mL. These two injections promoted RBL-2H3 cells to release histamine andβ-hexosaminidase at higher concentrations (P<0.05,P<0.01) in a dose dependent manner. Cell morphology showed a decrease of villous on the cell surface and an increase of the internal vacuolated structure. Both injections caused the blue ears of all animal with a rate of 100%. The quantity of Evans Blue of the extravasation was significantly increased (P<0.01). The results in vitro study were in close agreement with that in vivo.Conclusion Both QKL injection and XST injection may potentially cause anaphylactoid reactions. The RBL-2H3 cell model may be valuable to evaluate the anaphylactoid reactions induced by TCMI.

Replacing solubilizer with lipid microspheres eliminates the severe adverse reaction of vitamin K1 injection / 中国药学杂志

OBJECTIVE: To investigate whether substituting the solubilizer with lipid microspheres in vitamin K1 injection can eliminate the anaphylactoid reaction.

Allergic Reaction Following Insertion of Vancomycin Loaded in Bone Cement

Vancomycin bead is an important ancillary treatment for osteomyelitis caused by methicillin-resistant Staphylococcus aureus (MRSA). However, red-man syndrome, which can be a life-threatening complication of vancomycin, may occur from the use of vancomycin beads albeit rarely. We report our first case of red-man syndrome caused by vancomycin bead's insertion for chronic osteomyelitis. Symptomatic treatment was not effective and removal of the vancomycin beads seems to be the best treatment for this condition.

Antidote for acetaminophen poisoning: N-acetylcysteine

N-acetylcysteine (NAC) is widely recognized as the antidote of choice for acetaminophen overdose. Acetaminophen is a commonly used analgesic and antipyretic agent, and its use is one of the most common causes of poisoning worldwide. Acetaminophen toxicity may occur acutely when supratherapeutic amounts are ingested purposefully or unintentionally. Liver failure may occur in severe toxicity. However, if treated early, patients with acetaminophen poisoning generally recover uneventfully. Acetaminophen is metabolized to N-acetyl-p-benzoquinone imine (NAPQI), which is detoxified by conjugation with glutathione. In overdose, hepatic stores of glutathione are depleted and NAPQI binding to hepatocytes induces cell death and hepatic necrosis. NAC replenishes hepatic glutathione and may also act as a glutathione substitute, combining directly with the toxic metabolite. Intravenous NAC is indicated in patients who present with a history of acetaminophen overdose within the previous 8 to 10 hours, patients unable to tolerate oral NAC, and patients who present with evidence of fulminant hepatic failure. However, caution should be used in patients who have experienced previous hypersensitivity or anaphylactoid reactions to intravenous NAC, as well as in patients with asthma. The most common anaphylactoid reactions include rash, flushing, and bronchospasm. Adults should receive 150 mg/kg administered for 45 minutes, followed by 50 mg/kg administered for 4 hours, followed by 100 mg/kg administered for 16 hours. The total dose is 300 mg/kg delivered over 21 hours. Additionally, caution should always be used when intravenous NAC is prescribed and the amount of diluent is calculated. Monitoring of patients with a should include repeated neurologic and hemodynamic assessment.