Use of anti-digoxin antibodies in digitalis poisoning in an infant

Digitalis poisoning is rare, always iatrogenic and potentially lethal in infants. We report one case of severe poisoning in which treatment with digoxin Fab antibody fragments was successful. Evolution of plasma digitoxin levels showed an initial rapid decrease (T 1/2:1 hour), then a slower decline (T 1/2:5.5 days). No undesirable side-effects were observed.     

Immunopharmacologic treatment of 9 digitalis poisonings in children with sheep antidigoxin Fab

A report is presented of the clinical experience in the treatment of severe digitalis poisoning in nine young children aged 1 month to 4 years with digitalis antibody fragments (Fab). In 8 cases, accidental poisoning was involved, and in one case there was overdosage during the course of treatment. Digoxin preparations had been taken by 8 of the cases, 6 times in liquid form, and in one case digitoxin. Reliable signs for the ingestion of digitalis with high concentrations in the serum and the appearance of life-threatening disorders of rhythm or conduction were taken as the indication for the use of Fab. The Fab dose was 80 to 480 mg per case treated and was adjusted according to the quantity of glycoside ingested. All of the children recovered completely. Regression of the arrhythmias and improvement of the clinical condition were seen during or shortly after administration of the Fab infusion. In the serum there was a rapid fall in the level of free digoxin and a simultaneous marked rise in that of bound inactive digoxin. The digoxin was excreted in the urine in the bound form. Tolerance was good. No allergic reactions to foreign protein or later reactions in the form of serum sickness were observed.     

抗呼吸道合胞病毒Fab噬菌体抗体库的构建及初步筛选

目的：该研究旨在利用噬菌体展示技术，构建小儿呼吸道合胞病毒感染患者人源性噬菌体抗体库，搭建人源性抗体制备的技术平台，解决鼠源性单克隆抗体临床应用的不足，为小儿呼吸道合胞病毒感染发病机制的研究、诊断、治疗和预防提供新的有效途径。方法：从52例呼吸道合胞病毒感染患儿外周血淋巴细胞中提取总RNA，并逆转录为cDNA。用PCR扩增轻链和重链Fd段（即重链的可变区和第一恒定区）基因，并将扩增的轻链和重链基因片段克隆于pComb3x噬粒载体，电转化XL1-Blue大肠杆菌，经辅助噬菌体M13K07超感染后构建成Fab段噬菌体抗体库。对此抗体库双酶切进行鉴定，并用呼吸道合胞病毒颗粒作抗原进行初步筛选。结果：经过重轻链基因的重组，成功构建一免疫噬菌体抗体基因库，共有2.08×107个不同的克隆菌，其中70%的克隆均含有轻链和重链Fd 基因。因此，所构建的噬菌体抗体库的库容量为1.46×107，经过滴定，原始抗体库的滴度为1.06×1012 pfu/mL。经初步筛选，抗体库得到了不同程度的富集。结论：利用基因重组技术和噬菌体展示技术，成功构建了小儿呼吸道合胞病毒感染患者人源性Fab噬菌体抗体库，为人源性单克隆抗体的制备提供了良好的条件，为进一步的研究奠定了基础，亦将有益于小儿呼吸道合胞病毒感染的诊断、治疗和预防。     

Digitalis intoxication during the neonatal period: role of dehydration]

BACKGROUND: Despite the great progress which has been made in the treatment of acute digitalis intoxication by digoxin-immune Fab, it still remains a severe complication of cardiotonic therapy. CASE REPORT: A neonate with ventricular septal defect and large left-to-right shunt was treated with digitalis and diuretics at the usual starting doses. An intensive phototherapy was also required because of a hyperbilirubinemia due to glucose-6-phosphate dehydrogenase deficiency. Toxic digoxin accumulation (plasma level 14 ng/mL) was diagnosed three days after the initiation of treatment by the presence of sinus bradycardia and bursts of ventricular fibrillation. Intravenous administration of digoxin-specific antibody Fab fragments (Digidot) was effective, with a rapid improvement of the digitalis poisoning. CONCLUSION: Because of the particularities concerning drug distribution, metabolism and elimination of drugs in the neonatal period, the digoxin therapeutic index is narrow. This case report suggests the involvement of phototherapy and diuretics, which might induce a significant decrease in extracellular water and drug distribution volumes, ultimately promoting the occurrence of an intoxication.     

Pflanzenvergiftungen im Kindesalter

Each summer the number of patients presenting with possible poisoning after ingestion of berries or other plant parts increases sharply. In contrast to former practice, nowadays the vast majority of accidental plant ingestions can go untreated. In order to prevent unnecessary and potentially dangerous therapeutic measures, rapid risk assessments—often on the basis of fragmentary anamnestic information—are mandatory. Appropriate action can only be taken if the nurse or the doctor have a rough idea of the few poisonous plants requiring immediate action after accidental exposure. It should be kept in mind that the spectrum of accidental pediatric plant poisoning has undergone substantial changes during the last decade.     

Plant poisoning : A hospital-based study in Sri Lanka

This is a prospective hospital based study of 148 cases of plant poisoning seen by the author during a 12 year period. All cases were accidental. There were 2 deaths. Some measures to reduce the incidence of plant poisoning in Sri Lanka are listed.     

Massive digitoxin intoxication treated with digoxin-specific antibodies in a child

Summary A 20-month-old girl with massive digitoxin intoxication (initial digitoxin serum level: 629 ng/ml) was successfully treated with digoxin-specific antibody fragments (Fab). She presented with moderate signs of digitalis toxicity (somnolence, bradycardia, first-degree AV block) and improved rapidly during fractional Fab administration. Free serum-digitoxin disappeared after 6 vials of Fab (480 mg), but was measurable again on days 6 and 7. This case demonstrated that digoxin-specific antibodies, despite a 30–100 times lesser affinity for digitoxin, are effective in massive digitoxin intoxications. A rebound phenomenon may occur several days later and should be taken into consideration.     

New and novel antidotes in pediatrics

Antidotal therapy can be lifesaving in the management of poisoned children. Although supportive care is sufficient in many cases, a specific antidote can significantly reduce morbidity and mortality in a number of poisoning scenarios, and so the pediatric emergency medicine practitioner must be familiar with its indications for use, dosage and administration, and contraindications. A number of new antidotes have emerged in recent years. This review discusses the pediatric uses and limitations of intravenous N-acetylcysteine, octreotide, crotaline Fab antivenom, fomepizole, atropine and pralidoxime autoinjectors and provides some brief discussion on newer antidotes for which data is only starting to emerge.     

Childhood poisoning in Sri Lanka

Poisoning in children is a common accident and poison information services should be aware of the toxic agents responsible for poisoning in the community. A retrospective hospital based study was performed, before-the establishment of the National Poisons Information Centre in Sri Lanka. There were 4,556 admissions of poisoning to the selected hospitals in the Western Province in 1986 and of this, 540 (11.4%) were below 15 years. Males accounted for 66%. Kerosene oil was responsible for 47% of the poisoning cases in less than 5 years age group, while kerosene oil, pesticides and plants/mushrooms were the commonest toxic agents in the 5 to 14 years age group. The case fatality rate was 3.2%.     

Early tubular involvements in lead poisoning in children]

One of the main targets of lead poisoning is the kidney. Chronic poisoning can lead to kidney failure, and acute poisoning to tubulopathy with Toni-Debré-Fanconi syndrome. The primum movens of this tubulopathy is a distortion of mitochondrial energetic metabolism. We studied 27 children presenting with non symptomatic poisoning. Serum creatinine levels were normal. There was neither proteinuria nor glycosuria and only one child presented with hyperaminoaciduria. One third already presented with signs of tubulopathy, as shown by an increase in beta 2 microglobinuria in 36.5% of the cases studied (8 times in 22 samples) and enzymuria in 30.4% of the cases (23.5% if one excludes the children having had a chelation before the study). Kidney is therefore involved early in lead poisoning in children.     

Poisoning in children: Indian scenario

The retrospective data on childhood poisoning from eight regional hospitals in India has been reviewed. The demographic features and types of poisonings encountered have been compared. The analysis of the data indicated that pediatric poisonings constituted 0.23–3.3% of the total poisoning. The mortality ranged from 0.64–11.6% with highest being from Shimla. Accidental poisoning was common involving 50–90% of children below 5 years of age and males outnumbered the females. Suicidal poisoning was seen after 13 years of age and was due to drugs and household chemicals. One of the hospitals in Delhi recorded a very high incidence (66.6%) of drug poisoning in children. The drugs consumed belonged to phenothiazines, antiepileptics and antipyretics. Iron poisoning was seen in younger children. Kerosene was one of the causes of accidental poisoning at all hospitals except Shimla and rural Maharashtra where probably wood charcoal is widely used. Pesticide poisoning was more prevalent in Punjab and West Bengal whereas plant poisoning was very common in Shimla. Significant number of snake envenomation has been recorded from rural Maharashtra. Other less common accidental poisonings in children included alcohol, corrosives, heavy metals, rodenticides, detergents and disinfectants. Thus various regions in the country showed some variation in types and frequency of childhood poisoning which could be attributed to different geographical and socio-economic background.     

Poisoning in children.

This study is a retrospective analysis of 670 cases of poisoning (including phenothiazine toxicity) admitted to this hospital in the past six years, accounting for 0.9% of all pediatric admissions. Nearly half (45%) of the cases were in the age group of 1-4 years. Medicines and chemicals were the commonest agents (53%), followed by pesticides (15%), kerosene (11.2%), plant poisons (9.4%), food poisoning (3.9%) and corrosives (1.9%). Accidental poisoning was the commonest (70%) followed by iatrogenic (29.6%) and suicidal (0.4%). Overall mortality was 1.8%. Stress is laid on judicious use of phenothiazines as antiemetics and replacing them with drugs of lesser toxicity.     

Adolescent risk factors for poisonings - a prospective cohort study

Aim: This study assessed whether adolescents’ socioeconomic background, health and health behaviours are associated with later risk of poisoning hospitalization. Methods: A prospective cohort of 54 169 Finns aged 14–18 years was followed for an average of 10.6 years. The end‐point of the study was poisoning hospitalization, death or termination of follow‐up in 2001. The relationships of socioeconomic background, health and health behaviour characteristics with poisoning hospitalization were studied with adjusted Cox’s proportional hazard model. Results: We identified 443 persons (0.8%) with a diagnosed poisoning leading to hospital admission. The mean age at the time of the poisoning hospitalization was 22.7 years. The strongest risk factors for poisoning hospitalization in males were more than three stress symptoms weekly (HR 1.9), poor school success (HR 1.9) and not living with both of the parents in adolescence (HR 1.8). In females, the strongest risk factors were more than three stress symptoms weekly (HR 2.1), poor school success (HR 2.2) and recurring drunkenness as drinking style (HR 1.7). Conclusion: Poor school performance, health and health‐compromising behaviour adopted in adolescence are associated with a poisoning hospitalization risk in adulthood. Daily smoking and recurring drunkenness were strongly associated with a later poisoning hospitalization.     

Acute poisoning caused by the herbicide dichlorprop (preparation SYS 67 PROP)

We report on the acute poisoning of a 5-year-old boy by the herbicide "dichlorprop". This preparation is described as an effective means of plant protection. The effects of the intoxication were established by changes observed in almost all of the child's organs. The predominant effect was haemolytic anemia. All the pathological parameters regressed as a result of symptomatic therapy. General conclusions are drawn about intoxication, especially by means of plant protection agents.     

Common Childhood Poisonings and Their Outcome in a Tertiary Care Center in Delhi

Clinical profile of children presenting with poisoning to the Pediatric emergency department of a tertiary care hospital in Delhi from 8.1.2009 to 8.10.09 was studied prospectively. Fifty two cases of accidental poisoning were reported during this period which formed 1.05 % of all pediatric admissions (5094 admissions). No case of homicidal poisoning was reported. There were 80.7 % children between 1–5 y of age with male preponderance. PICA was observed in 57.7 % children. Overall mortality was 7.7 % and 11.3 % children required pediatric intensive care unit (PICU). Kerosene oil poisoning remained the commonest accidental poisoning in this study. An interesting trend was concentrated HCL poisoning (now a common household product) as the second commonest poisoning (17.3 %). This was followed by poisoning with various drugs used by adults in the house.     

Jatropha curcas-poisoning

Jatropha curcas is common plant found all over India more commonly in the southern parts. Though it is a common cause of accidental poisoning among children in these parts, standard texts rarely cover it. Gastrointestinal manifestations are predominant feature of poisoning with the seeds of Jatropha curcas. Mortality is rare.     

Poisoning deaths among Finnish children from 1969 to 2003

Aim:  Trends in paediatric deaths due to poisoning are little studied. The aim of this study was to investigate the cause and secular trend of poisoning deaths among Finnish children.
Methods:  Death certificates of all Finnish children aged 0–15 who died due to poisoning between 1969 and 2003 were obtained from the Statistics of Finland and analysed.
Results:  During the study period, altogether 121 children aged 0–15 years died from poisoning in Finland. Among 0- to 4-year olds, the incidence of poisoning deaths declined to practically zero by the beginning of 1980s. Most of these deaths were unintentional poisonings. Among 5- to 15-year olds, the incidence of poisoning deaths varied during the study period. In this age group, up to 53% of the deaths were suicides among girls compared with 20% among boys (p = 0.017). The corresponding figures for substance abuse were 54% among boys and 9% among girls (p < 0.001).
Conclusion:  Despite the declining secular trend seen in paediatric poisoning deaths in Finland from 1969 to 2003, the risk of death from both intentional and unintentional poisoning persists in children. Health programmes should be continued especially to promote well-being in families and to prevent teenage suicides and substance abuse.     

Spectrum of poisonings among children in Afghanistan

Two hundred and ten cases of poisoning were seen during a 2-year study period accounting 1.2 per cent of all children hospitalised for medical disorders. About 80 per cent of children were under 5 years of age. Poisoning due to various therapeutic agents was commonest (67.1%) followed by chemical agents (10%), hydrocarbons (8.6%), plants (6.7%), food (5.7%) and carbon monoxide gas (2.4%). Overdosage due to wrong advice of the Physician or ignorance of mother was responsible for drug poisoning in 46.8 per cent of all poisonings due to medicaments. Chlorpromazine alone accounted for 33.3 percent cases of drug poisonings. The mortality rate was 3.3 percent and all deaths were apparently due to home made or proprietary drug formulations.     

Radiology of kerosene poisoning in young children

Chest radiographs of 75 Nigerian children with kerosene poisoning were studied. The commonest pulmonary abnormality, found in 77% of cases, was basal infiltrates. There were more severe lung changes than in previous reports. A striking seasonal variation in kerosene poisoning was observed. Interestingly, air oesophagogram and gaseous distension of the stomach were demonstrated in 23 and 25% of patients, respectively. Probable factors in pathogenesis are discussed.