Intravenous acetylcysteine in paracetamol induced fulminant hepatic failure: a prospective controlled trial.

OBJECTIVE--To see whether intravenous acetylcysteine would improve outcome in patients with fulminant hepatic failure after paracetamol overdose. DESIGN--A prospective randomised controlled study. SETTING--The Institute of Liver Studies, King''s College Hospital, London. PATIENTS--50 consecutive patients (21 male) aged 16-60 with fulminant hepatic failure after paracetamol overdose who had not previously received acetylcysteine. INTERVENTIONS--Conventional intensive liver care plus either acetylcysteine (25 patients) in the same dose regimen as used early after a paracetamol overdose, except that the infusion was continued until recovery from encephalopathy or death, or an equivalent volume of 5% dextrose (25 patients). MAIN OUTCOME MEASURES--Survival; incidence of cerebral oedema, renal failure, and hypotension requiring inotropic support; liver function as assessed by prolongation of the prothrombin time; and degree of encephalopathy. RESULTS--The rate of survival was significantly higher in the acetylcysteine treated group than in the controls (48% (12/25 patients) v 20% (5/25); p = 0.037, 95% confidence interval for difference in proportions surviving 3% to 53%). Acetylcysteine treated patients had a lower incidence of cerebral oedema (40% (10/25) v 68% (17/25); p = 0.047, 95% confidence interval for difference in incidence 2% to 54%), and fewer developed hypotension requiring inotropic support (48% (12/25) v 80% (20/25); p = 0.018, 95% confidence interval 7% to 57%). Rates of deterioration and recovery of liver function, however, were similar in the two groups. No adverse reactions to acetylcysteine were seen. CONCLUSIONS--Acetylcysteine is safe and effective in fulminant hepatic failure after paracetamol overdose.     

Mechanisms for an effect of acetylcysteine on renal function after exposure to radio-graphic contrast material: study protocol

Background

Contrast-induced nephropathy is a common complication of contrast administration in patients with chronic kidney disease and diabetes. Its pathophysiology is not well understood; similarly the role of intravenous or oral acetylcysteine is unclear. Randomized controlled trials to date have been conducted without detailed knowledge of the effect of acetylcysteine on renal function. We are conducting a detailed mechanistic study of acetylcysteine on normal and impaired kidneys, both with and without contrast. This information would guide the choice of dose, route, and appropriate outcome measure for future clinical trials in patients with chronic kidney disease.

Methods/Design

We designed a 4-part study. We have set up randomised controlled cross-over studies to assess the effect of intravenous (50 mg/kg/hr for 2 hrs before contrast exposure, then 20 mg/kg/hr for 5 hrs) or oral acetylcysteine (1200 mg twice daily for 2 days, starting the day before contrast exposure) on renal function in normal and diseased kidneys, and normal kidneys exposed to contrast. We have also set up a parallel-group randomized controlled trial to assess the effect of intravenous or oral acetylcysteine on patients with chronic kidney disease stage III undergoing elective coronary angiography. The primary outcome is change in renal blood flow; secondary outcomes include change in glomerular filtration rate, tubular function, urinary proteins, and oxidative balance.

Discussion

Contrast-induced nephropathy represents a significant source of hospital morbidity and mortality. Over the last ten years, acetylcysteine has been administered prior to contrast to reduce the risk of contrast-induced nephropathy. Randomized controlled trials, however, have not reliably demonstrated renoprotection; a recent large randomized controlled trial assessing a dose of oral acetylcysteine selected without mechanistic insight did not reduce the incidence of contrast-induced nephropathy. Our study should reveal the mechanism of effect of acetylcysteine on renal function and identify an appropriate route for future dose response studies and in time randomized controlled trials.

Trial registration

Clinical Trials.gov: NCT00558142; EudraCT: 2006-003509-18.     

Meconium ileus equivalent in adults with cystic fibrosis of pancreas: a report of six cases.

Eleven episodes of "meconium ileus equivalent" have been seen in six adults with cystic fibrosis of the pancreas. Three patients were initially treated surgically; one died and the other two developed serious postoperative chest infections. Six episodes were successfully treated medically with acetylcysteine orally and by enema, nasogastric suction, and intravenous fluids. Operation should be avoided if possible, and maintenance treatment with acetylcysteine may be necessary to prevent relapse.     

Treatment of acetaminophen poisoning.

Acetaminophen is an analgesic that is frequently used in Canada, and the occurrence of overdoses with this drug seems to be increasing. The most serious complication of acetaminophen overdose is hepatic failure. Because of pathophysiologic effects of acetaminophen poisoning and the mechanisms of its toxic effects are now better understood, a rational approach to treatment is possible. Several precursors of glutathione, acetylcysteine in particular, are effective in preventing liver damage if administered within 10 hours of acetaminophen ingestion. Plasma acetaminophen levels are a helpful guide to therapy.     

Unexpected overdose with diltiazem: value of toxicological screening

We describe a 59-year-old woman who was admitted in deep coma with bradycardia, hypotension and fixed pupils. The cause of her severe condition was unclear. Cerebral and myocardial infarction was excluded. Temporary transcutaneous pacing was not successful, nor was atropine or norepinephrine (noradrenaline), but the patient responded well to isoprenaline infusion. Since she was known to have a psychiatric history, toxicological screening was performed which showed a severe diltiazem overdose. Later we discovered that she took diltiazem for angina pectoris. The patient survived and was discharged without neurological or cardiological deficits after two days of treatment. This case report emphasises the importance of toxicological screening in unconscious patients with no apparent cause. We review the clinical features and treatment options of diltiazem overdose and discuss the value of toxicological screening.     

Autonomic function following acute organophosphorus poisoning: a cohort study

Autonomic dysfunction after chronic low level exposure to organophosphorus (OP) pesticides has been consistently reported in the literature, but not following a single acute overdose. In order to study autonomic function after an acute OP overdose, sixty-six overdose patients were compared to 70 matched controls. Assessment of autonomic function was done by heart rate response to standing, deep breathing (HR-DB) and Valsalva manoeuvre; blood pressure (BP) response to standing and sustained hand grip; amplitude and latency of sympathetic skin response (SSR); pupil size and post-void urine volume. The patients were assessed one and six weeks after the exposure. The number of patients who showed abnormal autonomic function compared to standard cut-off values did not show statistically significantly difference from that of controls by Chi-Square test. When compared to the controls at one week the only significant differences consistent with autonomic dysfunction were change of diastolic BP 3 min after standing, HR-DB, SSR-Amplitude, SSR-Latency, post-void urine volume and size of the pupil. At 6 weeks significant recovery of autonomic function was observed and only HR-DB was decreased to a minor degree, -5 beats/min [95%CI 2-8]. This study provides good evidence for the lack of long term autonomic dysfunction following acute exposure to OP pesticides.     

Glycemia and Immune Responses

The intensity of experimental and clinical immune responses was correlated with the degree of glycemia of the reacting subject. Hyperglycemias resulting from overdosage with sugars, cortisol, adrenaline, or from diabetes inhibit the anaphylactoid reactions; anaphylaxis, and the tuberculin reaction; but potentiate infections. Hypoglycemias resulting from fasting, insulin and adrenalectomy potentiate the anaphylactoid reactions, anaphylaxis, and the tuberculin reaction; but inhibit infections. The hypothesis is proposed that hyperglycemia inhibits certain antigen-antibody combinations; this results in an inhibition of hypersensitivity, but an aggravation of infection.     

New Therapeutic Approach: Diphenyl Diselenide Reduces Mitochondrial Dysfunction in Acetaminophen-Induced Acute Liver Failure

The acute liver failure (ALF) induced by acetaminophen (APAP) is closely related to oxidative damage and depletion of hepatic glutathione, consequently changes in cell energy metabolism and mitochondrial dysfunction have been observed after APAP overdose. Diphenyl diselenide [(PhSe)₂], a simple organoselenium compound with antioxidant properties, previously demonstrated to confer hepatoprotection. However, little is known about the protective mechanism on mitochondria. The main objective of this study was to investigate the effects (PhSe)₂ to reduce mitochondrial dysfunction and, secondly, compare in the liver homogenate the hepatoprotective effects of the (PhSe)₂ to the N-acetylcysteine (NAC) during APAP-induced ALF to validate our model. Mice were injected intraperitoneal with APAP (600 mg/kg), (PhSe)₂ (15.6 mg/kg), NAC (1200 mg/kg), APAP+(PhSe)₂ or APAP+NAC, where the (PhSe)₂ or NAC treatment were given 1 h following APAP. The liver was collected 4 h after overdose. The plasma alanine and aspartate aminotransferase activities increased after APAP administration. APAP caused a remarkable increase of oxidative stress markers (lipid peroxidation, reactive species and protein carbonylation) and decrease of the antioxidant defense in the liver homogenate and mitochondria. APAP caused a marked loss in the mitochondrial membrane potential, the mitochondrial ATPase activity, and the rate of mitochondrial oxygen consumption and increased the mitochondrial swelling. All these effects were significantly prevented by (PhSe)₂. The effectiveness of (PhSe)₂ was similar at a lower dose than NAC. In summary, (PhSe)₂ provided a significant improvement to the mitochondrial redox homeostasis and the mitochondrial bioenergetics dysfunction caused by membrane permeability transition in the hepatotoxicity APAP-induced.     

雾化吸入不同剂量盐酸乙酰半胱氨酸溶液联合阿米卡星治疗呼吸机相关性肺炎的效果及对患者血气指标和炎症因子的影响

摘要 目的：探讨雾化吸入不同剂量盐酸乙酰半胱氨酸溶液联合阿米卡星治疗呼吸机相关性肺炎的效果及对患者血气指标和炎症因子的影响。方法：选取我院2020年1月到2023年1月收治的98例呼吸机相关性肺炎患者作为研究对象,应用随机数字表法将其分为对照组（n=38）、观察A组（n=30）与观察B组（n=30）。对照组采用阿米卡星注射液静脉滴注,观察组A组在对照组基础上采取3 mL盐酸乙酰半胱氨酸溶液雾化吸入,观察B组在对照组基础上采取6 mL盐酸乙酰半胱氨酸溶液雾化吸入,对比三组患者临床疗效、血气指标、炎症因子水平以及不良反应发生率。结果：观察B组和观察A组治疗总有效率明显对照组,且观察B组治疗总有效率明显高于观察A组（P＜0.05）;三组患者治疗前动脉血二氧化碳分压（PaCO₂）、动脉血氧分压（PaO₂）水平对比无明显差异（P＞0.05）,治疗后三组患者PaO₂均升高,且观察B组和观察A组明显高于对照组,观察B组高于观察A组（P＜0.05）,PaCO₂均降低且观察B组和观察A组明显低于对照组,观察B组低于观察A组（P＜0.05）;三组患者治疗前白细胞计数（WBC）、中性粒细胞百分比（GRA）、降钙素原（PCT）、C反应蛋白（CRP）、血沉（ESR）表达水平对比无明显差异（P＞0.05）,治疗后三组患者WBC、GRA、PCT、CRP、ESR表达水平均降低,且观察B组和观察A组明显低于对照组,观察B组高于观察A组（P＜0.05）;三组患者不良反应发生率对比无明显差异（P＞0.05）。结论：对呼吸机相关性肺炎患者采用雾化吸入盐酸乙酰半胱氨酸溶液联合阿米卡星治疗效果显著,但采取6 mL剂量能够进一步改善患者呼吸功能,降低患者机体炎症因子表达水平,且安全性较高。     

吡非尼酮联合乙酰半胱氨酸治疗IPF患者的疗效及机制分析

目的:探讨吡非尼酮联合乙酰半胱氨酸治疗特发性肺纤维化(idiopathic pulmonary fibrosis,IPF)患者的疗效及可能机制.方法:选择2018年1月至2020年1月我院收治的78例IPF患者,根据随机数字表法将其分为观察组(38例)及对照组(40例).对照组患者给予吡非尼酮,观察组给予吡非尼酮联合乙...     

Plasma prostaglandin E2 level in Kawasaki disease

Plasma levels of prostaglandin E2 and prostaglandin F2 alpha were determined in 15 patients in the acute and recovery stages of Kawasaki disease, 10 patients with anaphylactoid purpura, 16 with bacterial and viral infections and 10 healthy children. Plasma levels of prostaglandin E2 were markedly increased in the acute stage of Kawasaki disease, and these levels were decreased in the recovery stage. The prostaglandin F2 alpha/prostaglandin E2 ratio in the acute stage of Kawasaki disease was markedly decreased. Plasma levels of prostaglandin E2 in patients with anaphylactoid purpura, bacterial and viral infections were within the normal range. In Kawasaki disease which is associated with systemic vasculitis with a severe inflammatory reaction, prostaglandin E2 is considered to be more selectively produced and released than prostaglandin F2 alpha, suggesting that prostaglandin E2 plays an important role in the immunological and inflammatory reaction.     

Acute Sirolimus Overdose: A Multicenter Case Series

BackgroundThere are few data relating to sirolimus overdose in the medical literature. Our objectives were to describe all cases of overdose with sirolimus reported to Swiss, German and Austrian Poisons Centres between 2002-2013.MethodsAn observational case-series analysis was performed to determine circumstances, magnitude, management and outcome of sirolimus overdose.ResultsFive cases of acute sirolimus overdose were reported – three in young children and two in adults. Four were accidental and one was with suicidal intent. Two patients developed symptoms probably related to sirolimus overdose: mild elevation of alkaline phosphatase, fever and gastroenteritis in a 2.5-year-old male who ingested 3 mg, and mild changes in total cholesterol in an 18-year-old female after ingestion of 103 mg. None of these events were life-threatening. Serial blood concentration measurements were performed starting 24 h after ingestion of 103 mg in a single case, and these followed a similar pharmacokinetic time-course to measurements taken after dosing in the therapeutic range.ConclusionsAcute sirolimus overdose occurred accidentally in the majority of cases. Even large overdoses appeared to be well-tolerated, however children might be at greater risk of developing complications. Further study of sirolimus overdose is needed.     

The protective effect of prolil-glycil-proline peptide (PGP) under compound 48/80-induced anaphylactoid reaction in mice

The influence of PGP on compound 48/80-induced anaphylactoid reaction development in mice and on histamine secretion from rat peritoneal mast cells (RPMS) under their activation by compound 48/80 were investigated. Anaphylactoid reaction was caused by intraperitoneal injection of compound 48/80 into mice. The number of animals with manifestations of anaphylactoid reaction symptoms, the severity of these symptoms, the amount of died animals and the time of death were registering during an hour. Mast cells for in vitro investigations were obtained from rats’ peritoneal cavity. Secreted histamine was evaluated from formation of fluorescent product of it’s condensation with ortho-phthalaldehyde. The preventive injection of PGP in mice (15 min before compound 48/80) decreased the mortality rate of animals and intensity of anaphylactoid reaction symptoms. But PGP had no effect on histamine secretion from mast cells under their activation by compound 48/80 in vitro. Results show that there is a component in the mechanism of PGP protective effect under anaphylactoid reaction which is not connected with mast cells stabilization.     

Acute drug poisoning in the adult

In a prospective study of 349 patients with acute poisoning treated at The Montreal General Hospital in 1972 benzodiazepines and non-barbiturate hypnotics were found to be the most frequent putative drugs. Of the 108 patients admitted to hospital 37% had taken an overdose of a drug prescribed for them by their psychiatrist or other physician; 48% had formerly taken an overdose of drugs and 44% had had previous psychiatric treatment. Unconsciousness, respiratory depression, metabolic acidosis and acidemia, and hypokalemia were the most frequent clinical abnormalities observed. Treatment was supportive. There were six deaths. The average duration of coma was short; only five surviving patients remained unconscious for more than 24 hours. Respiratory complications were frequent.It is recommended that more attention be paid to recognizing patients whose behaviour pattern might include such an impulsive gesture, and that alternatives be found for barbiturate and non-barbiturate hypnotics.     

Acute Thiopurine Overdose: Analysis of Reports to a National Poison Centre 1995–2013

Literature regarding acute human toxicity of thiopurines is limited to a handful of case reports. Our objectives were to describe all cases of overdose with thiopurines reported to the Swiss Toxicological Information Centre between 1995–2013. A retrospective analysis was performed to determine circumstances, magnitude, management and outcome of overdose with these substances. A total of 40 cases (14 paediatric) were reported (azathioprine, n = 35; 6-mercaptopurine, n = 5). Of these, 25 were with suicidal intent, 12 were accidental and 3 were iatrogenic errors. The magnitude of overdose ranged from 1.5 to 43 (median 8) times the usual dose in adults. Twelve cases (30%) had attributable symptoms. The majority of these were minor and included gastrointestinal complaints and liver function test and blood count abnormalities. Symptoms were experienced by patients who took at least 1.5-times their usual daily thiopurine dose. Overdoses over two or more consecutive days, even if of modest size, were less well tolerated. One case of azathioprine and allopurinol co-ingestion over consecutive days led to agranulocytosis. Decontamination measures were undertaken in 11 cases (10 activated charcoal, 1 gastric lavage) and these developed fewer symptoms than untreated patients. This study shows that acute overdoses with thiopurines have a favourable outcome in the majority of cases and provides preliminary evidence that gastrointestinal decontamination with activated charcoal may reduce symptom development after overdose of these substances if patients present to medical services soon after ingestion.     

Vasculitis and anaphylactoid shock in mice induced by the polysaccharide fraction secreted into culture supernatants by the fungus Candida metapsilosis

The biological effects of Candida metapsilosis water-soluble fraction (CMWS), prepared using a completely synthesized medium, were examined to determine whether CMWS induces vasculitis similar to that seen in Kawasaki disease, and anaphylactoid shock, in mice. It was found that intraperitoneal injection of CMWS induces coronary arteritis and i.v. injection induces acute anaphylactoid shock in mice, similar to Candida albicans water-soluble fraction (CAWS)-induced arteritis and anaphylactoid shock. The mannan structure of the polysaccharide fraction was then analyzed by performing antiserum reactivity tests and nuclear magnetic resonance spectroscopy. The mannan structure was investigated because the present authors have recently found that the mannan moiety within the polysaccharide fraction might be responsible for these pathogenic activities. The structural analysis showed that the mannan structure within CMWS expresses α-mannan residues, but not β-mannan. In addition, the mannan structure of CMWS is quite similar to that of CAWS. The present findings indicate that the polysaccharide fraction from C. metapsilosis, which is mainly composed of mannan, contributes to coronary arteritis and acute shock, and that the mannan structure could be responsible for this pathogenicity.     

Adverse Reactions to Radiographic Contrast Material

Major adverse reactions to radiographic contrast media will occur more often as contrast material is now also administered during computerized tomographic (CT) scanning. Differentiation of the two major contrast reactions, the vagus reaction and the anaphylactoid reaction, is essential. Bradycardia is the key finding for identifying the vagus reaction. The vagus reaction involving hypotension and bradycardia requires treatment with large doses of atropine given intravenously. The immediate generalized reaction or anaphylactoid reaction should be treated as anaphylaxis with administration of vasopressors, fluids, steroids and antihistamines. Steroids and antihistamines given before the examination may offer protection to those high-risk patients who have had previous anaphylactoid reactions to contrast material.