Acute iron poisoning: management guidelines

Serum iron level may not be available and fully reliable in management decision and prognostication in our setting. An estimated ingestion of >60 mg/kg elemental iron, onset of symptoms, blood sugar >150 mg/dL, total leukocyte count >15,000 cumm and presence of iron tablets on abdominal radiograph indicates severe toxicity and need for chelation therapy. Appearance of "vin-rose" color urine following a dose of desferrioxamine may be helpful, but is not seen consistently after chelation therapy. Early decontamination of gut (gastric lavage/whole gut irrigation), desferrioxamine infusion (15 mg/kg/hour in saline), and aggressive management of shock, and organ failure preferably in a PICU are mainstay of management, and has improved the outcome. Shock, coagulopathy (prothrombin index <50%), severe acidosis and acute liver failure are poor prognostic indicators. Guardians should be counseled about safe storage of iron tablets made for adults, and general poisoning prevention measures.     

Early iron overload in beta-thalassaemia major: when to start chelation therapy?

Twenty-eight children with beta-thalassaemia major aged between 11 and 48 months were given intensive transfusions. Serum iron, transferrin saturation, serum ferritin, non-transferrin iron, and subcutaneous desferrioxamine-induced urinary iron excretion were measured. The results showed that even children with a limited number of transfusions had severe iron overload as indicated, in particular, by the raised serum ferritin levels and the high excretion rates after subcutaneous infusion of desferrioxamine. The desferrioxamine test was useful, even in very young children, in assessing response to chelation therapy thus enabling such treatment to be started early to prevent harm from iron overload.     

Non-transferrin-bound iron in long-term transfusion in children with congenital anemias

Non-transferrin-bound iron (NTBI), a potentially toxic compound, is increased in the serum of patients with iron overload and fully saturated transferrin. We found markedly elevated NTBI levels in 16 children (including nine with sickle cell disease and five with beta-thalassemia) with iron overload secondary to prolonged transfusion therapy. During iron chelation with subcutaneous desferrioxamine infusion, NTBI levels decreased to normal, but became elevated within 2 to 4 hours after discontinuation of desferrioxamine. NTBI causes hepatic and cardiac toxicity in experimental systems, but our patients lacked sufficient organ dysfunction for this association to be made. The use of continuous 24-hour chelation to maintain NTBI at low levels may prevent progressive iron toxicity in patients who first received chelation therapy at an older age or who already have evidence of cardiac damage.     

Aluminum intoxication in a child: treatment with intraperitoneal desferrioxamine

We report the successful chelation of aluminum and the clinical resolution of severe aluminum intoxication in an infant receiving chronic peritoneal dialysis through the use of intraperitoneal desferrioxamine. Following the introduction of desferrioxamine, urine and dialysate fluid aluminum levels exceeded those noted without the chelating agent, thus demonstrating enhanced removal of aluminum. As a result of therapy, plasma and bone aluminum levels decreased markedly, and previously noted histomorphometric abnormalities on bone biopsy resolved. Clinically, the aluminum-associated osteomalacia and microcytic hypochromic anemia completely reversed. Moderate developmental delay has also improved slightly but persists. Our experience suggests that intraperitoneal chelation therapy with desferrioxamine may be helpful to reverse aluminum intoxication in children with chronic renal failure. However, limited exposure to aluminum should remain a primary goal.     

A case of rhesus hemolytic disease with hemophagocytosis and severe iron overload due to multiple transfusions

BACKGROUND: A newborn with cholestatic hepatic disease and hemophagocytic lymphohistiocytosis due to rhesus hemolytic disease (RHD) is reported. OBSERVATION: A 34 weeks' gestation baby with RHD, who had received multiple intrauterine transfusions (IUT), developed cholestatic hepatic disease and secondary hemophagocytic lymphohistiocytosis (HLH). Her serum ferritin level increased to 5,527 ng/mL, and liver biopsy showed severe iron overload. Treatment with intravenous desferrioxamine resulted in a marked decrease in serum ferritin levels and normalization of liver function CONCLUSION: We suggest that patients who have undergone IUT be evaluated for hyperferritinemia. If hyperferritinemia is noted, chelation therapy should be considered. As another rare finding, HLH can complicate the course of RHD.     

Rare indications for iron chelation therapy with desferrioxamine]

In beta thalassaemia patients the subcutaneous desferrioxamine chelation therapy is performed routinely. Rare indications are hypoplastic anaemia, congenital dyserythropoetic anaemia and Fanconi anaemia. We initiated the chelation agent in three patients with the above mentioned diagnoses. The beginning of treatment in hypoplastic anaemia depends upon the quantity of red cell transfusions, whereas in dysterythropoetic anaemia the increased intestinal iron absorption has to be taken into consideration. Aim of the therapy is a negative iron balance. The evaluation of the iron balance is relatively simple. The girl with hypoplastic anaemia has been treated for 1.5 years. Within this time she received 11,680 mg iron by blood transfusions. The urinary iron output was 7112 mg. Depending on the analyzing method, the mean fecal iron excretion amounts 36.5% or 61% of the global excretion. Laboratory findings and clinical course are in favour to the aimed negative iron balance in two patients.     

Acute iron ingestion

Objective : Intoxication is one of the most common causes of admissions to emergency department in pediatric age group. Incidence of iron poisoning gradually increased because of wide spread use of iron containing drugs.Method : In this report, we present five cases of iron ingestion who were admitted to our emergency department within a year.Result : Whole bowel irrigation in addition to gastric lavage with an iron dose of over 50mg/kg as well as deferoxamine treatment for patients in whom clinical and laboratory indications are present.Conclusion : The prompt recognition and treatment of children with acute iron poisoning is the single and the most critical point for decreasing the morbidity and mortality associated with iron containing products.     

小儿急性中毒的特点和诊治进展

儿童急性中毒的发生与周围环境密切相关.我国儿童急性中毒以农药、药物和灭鼠药为主,主要因误服误食所致,重症急性中毒的病死率仍较高.加强对药物和上述毒物的管理,可以从源头减少中毒机会.对疑似中毒的患儿,除详细询问病史和查体外,多数情况下毒物鉴定是明确有元中毒和病情严重程度最直接、客观的方法.及时诊断、合理使用解毒药物、普及血液净化治疗技术、重视支持疗法是成功救治的关键.准确而全面的临床流行病学资料有助于对地区性、年龄阶段性及不同性别的中毒起到警示作用.     

Restoration of hematopoiesis after iron chelation therapy with deferasirox in 2 children with severe aplastic anemia

Iron overload is a significant clinical problem in patients with severe aplastic anemia or other transfusion-dependent bone marrow failure diseases. Iron chelation therapy is more readily available owing to the recent introduction of oral iron chelators. We describe 2 cases of children with severe aplastic anemia and related transfusional iron overload who received iron chelation therapy with oral deferasirox. Our patients experienced restoration of trilineage hematopoiesis after the administration of deferasirox along with the reduction in ferritin levels, and subsequently became transfusion-free. Our report raises the possibility of potential benefit on hematopoiesis from iron chelation therapy and warrants furthermore investigations.     

Unrelated hematopoietic stem cell transplantation in a patient with congenital dyserythropoietic anemia and iron overload

CDA is a heterogeneous group of disorders that result in morphologically abnormal erythroid maturation and ineffective erythropoiesis. Curative therapy for CDA focuses on the use of HSCT using fully matched sibling donors. This is the first report of a Type II CDA patient with severe iron overload who was successfully treated with HSCT using a HLA-matched unrelated donor after aggressive chelation therapy. Given the challenges of HSCT in any patient with CDA and severe iron overload, the role of novel approaches to iron chelation and HSCT is discussed.     

The total iron-binding capacity in iron poisoning. Is it useful?

Traditionally, a serum iron concentration in excess of the total iron-binding capacity (TIBC) is considered as an indication for deferoxamine therapy in acute iron poisoning. We observed a reversible elevation of the TIBC in patients with iron poisoning that coincided with their acute hyperferremia and have hypothesized that this is a laboratory aberration. We tested this hypothesis in vitro and found that the addition of iron to test serum samples produced a related increase in the TIBC, and alteration of the assay by providing additional adsorbent prevented this occurrence. We also evaluated the reproducibility of the TIBC as performed by 500 laboratories on 10 different reference samples. The mean coefficient of variation was 16%, which was unsatisfactory. We concluded that the TIBC should not be used in the decision for the initiation of deferoxamine therapy in acute iron poisoning. Furthermore, high TIBC values that are occasionally seen in patients with iron poisoning should not be considered as providing a protective effect.     

Severe lead poisoning in pregnancy.

BACKGROUND: Lead freely crosses the placenta. Consequently, gestational lead poisoning is not only harmful to the woman but also to the developing fetus, invariably producing congenital lead poisoning. The scope and consequences of severe lead poisoning in pregnancy (blood lead level > or =45 microg/dL) have not been well characterized. METHODS: We reviewed our experience in the management of women with severe gestational lead poisoning. Additionally, we reviewed the literature on this disorder in an effort to identify patterns in etiology and outcome. RESULTS: Over a 3-year period treatment was provided to 7 severely lead-poisoned women. A 25-year review of the medical literature identified an additional 8 cases. Among these 15 women, 70% were Hispanic, all of whom developed lead poisoning from the ingestion of soil, clay, or pottery ("tierra"). Other sources of lead poisoning were paint chip ingestion (n = 2), household renovation, and use of a complementary-alternative medication (bone meal). Lead poisoning was discovered in the third trimester in 12 (86%) subjects after the women presented with subtle but characteristic findings of severe lead poisoning, including malaise, anemia, or basophilic stippling on blood smear; one woman was identified when she presented after a generalized seizure, having a blood lead level of 104 microg/dL. Five women received chelation therapy during pregnancy with CaNa(2) EDTA, dimercaprol, or succimer. At delivery mean maternal blood lead level was 55 microg/dL, whereas mean neonatal lead level was 74 microg/dL (P =.009). Thirteen neonates underwent chelation, all within the first 28 days of life. No infant in the current series had an identifiable birth defect. CONCLUSIONS: On the basis of this experience we conclude that severe lead poisoning in pregnant women has the following characteristics: 1) it most often occurs because of intentional pica, 2) its presenting features are subtle, often consisting only of malaise and anemia, and 3) blood lead levels in the neonate are higher than simultaneous maternal lead levels.     

Acute iron poisoning: clinical picture, intensive care needs and outcome

In this retrospective study, we examined the prevalence of acute iron poisoning among children attending Pediatric Emergency service of a teaching hospital, and studied their clinical profile, treatment and outcome to define intensive care needs. During the 5 years' study period of 27125 patient visits to Pediatric Emergency, 337 (1.2%) were for accidental poisoning. Of these 21(7%) patients had iron poisoning; 18 were transferred to PICU. Three patients were asymptomatic, others had vomiting (n =15, 83%), diarrhoea (n =13, 72%), malena (n = 8, 44%), and hemetemesis (n=6, 33%) generally within 6 hours of ingestion. Nine progressed to shock and/or impaired consciousness; two had acute liver failure. Dose of ingested iron and clinical signs were most useful guide to iron toxicity and management decisions; serum iron did not help. Gastric lavage yielded fragments of iron tablets in 10 patients. On desferrioxamine infusion Vin-rose colour urine was not seen in 31% even in presence of high serum iron. Shock responded to normal saline (33 +/- 15 mL/kg) and dopamine (10 +/- 4 microg/kg/min) within 4-24 hours in 7 of 9 patients. Presence of shock or acute liver failure with coagulopathy and/or severe acidosis predicted all the four deaths. Desferrioxamine infusion and supportive care of shock was the mainstay.     

Growth and development in thalassaemia major patients with severe bone lesions due to desferrioxamine

Nine transfusion-dependent -thalassaemia major patients (seven males and two females), aged 4–15 years, with growth retardation and severe rickets-like radiological lesions due to continuous subcutaneous chelation therapy with desferrioxamine (45–75 mg/kg body weight, 6–7 times/week), were seen in our centre during the last 8 years. Serum ferritin levels ranged from 976 to 4115 g/l. There was a progressive decline in growth velocity in these patients 2–3 years before the appearance of rickets-like radiological lesions. All patients underwent surgery to correct genu valgum and/or slipped capital epiphyses. The final height was below the 3rd percentile in six patients (SDS: from –2.9 to –5.2). The short stature was mainly due to a disproportion between upper and lower segments. Six of the patients had an associated sensorineural hearing loss.Conclusion Our data emphasize the importance of an accurate surveillance of the toxic effects of desferrioxamine treatment and warn of the risk of overtreating patients with low iron overload and also suggest a possible individual idiosyncrasy to the adverse effects of chelation therapy.     

Reversal of desferrioxamine induced auditory neurotoxicity during treatment with Ca-DTPA.

Auditory neurotoxicity occurred in 13 (26%) of 50 evaluable patients receiving long term desferrioxamine chelation. In five of these patients, all of whom were receiving high doses of desferrioxamine, the toxicity caused deafness. These five patients were treated with subcutaneous calcium diethylene triamine pentacetic acid (Ca-DTPA) with zinc supplements instead of desferrioxamine, and their hearing improved during periods of seven to 19 months. Their serum ion concentrations remained unchanged. We suggest that all patients receiving long term desferrioxamine should have audiometric assessments at 6-12 monthly intervals. Ca-DTPA with oral zinc supplements should be considered as alternative to desferrioxamine as an iron chelating treatment in patients with auditory neurotoxicity.     

Yersinia Infections in Patients with Homozygous Beta-Thalassemia Associated with Iron Overload and its Treatment

Patients with homozygous beta-thalassemia are at increased risk of serious infections. Yersinia enterocolitica is an organism with a predilection for these and other iron-overloaded patients. Three young adult patients with beta-thalassemia who were chronically transfused and developed yersiniosis are reported. Iron overload and desferrioxamine use are predisposing factors, as supported by clinical, animal, and in vitro data. Iron excess both immunologically compromises the host and greatly enhances yersinial growth. Desferrioxamine may make host iron even more bioavailable to Yersinia. Recognition of this association and unusual manifestations in these patients such as an appendicitis-like syndrome may direct clinicians to earlier antiyersinial therapy and temporary cessation of chelation.     

Etiology of acute lower respiratory tract infection

Objective : To identify pathogens responsible for acute severe lower respiratory tract infection (ALRTI) in under five children by non-invasive methods.Method : 95 children hospitalized with acute severe lower respiratory tract infection were investigated for identification of viruses, bacteria, chlamydia or mycoplasma by nasopharyngeal aspirates, blood culture and serology.Result : Etiological agents could be identified in 94% of the patients. Viruses from NP aspirate could be isolated in 36 (38%), bacterial isolates from blood cultures in 15(16%); mycoplasma was identified in 23(24%) and chlamydia in 10(11%) by serological tests; mixed infections were present in 8 (8%) patients.Conclusion : Noninvasive methods can be useful in identifying etiological agents in severe ALRTI     

What is new in iron overload?

Children with severe chronic hemolytic anemia or congenital erythroblastopenia are transfusion dependent. Long-term transfusion therapy prolongs life but results in a toxic accumulation of iron in the organs. The human body cannot actively eliminate excess iron. Therefore, the use of a chelating agent is required to promote excretion of iron. So far, iron chelation has been done by subcutaneous infusion of deferoxamine given over 10 h, 5–6 days per week. Compliance is poor and chelation often insufficient. Ferritin measurements and sometimes liver biopsies are used to evaluate the iron burden in the body. At the present time, new iron chelators that can be given orally are available. Furthermore, magnetic resonance imaging (MRI) assessment of tissue iron is a noninvasive and highly reproducible method, which is able to quantitate organ iron burden. In conclusion, iron overload can be measured more accurately with noninvasive methods such as MRI. Deferasirox is a once-daily oral therapy for treating transfusional iron overload, which improves patient compliance and quality of life.     

Present status and future prospects of oral iron chelation therapy in thalassaemia and other diseases

In the last few years we have witnessed the emergence of oral chelation which is a new form of therapy for transfusional iron-loaded patients in thalassaemia and other refractory anaemias. The need for a cheap, non-toxic, orally effective iron chelator is paramount because it could potentially save the lives of many thousands of patients. At present, less than 10% of the patients requiring iron chelation therapy worldwide receive the widely used chelating drug desferrioxamine (DF) because of its high cost, oral inactivity and toxicity. The most promising oral iron chelator is 1, 2-dimethyl-3-hydroxypyrid-4-one (L1 or INN: Deferiprone), which has so far been taken by over 450 patients in 15 countries, and in some cases daily for over 4 years with very promising results. L1 was shown at 50–100 mg/kg/day to be effective in bringing patients to negative iron balance. It increases urinary iron excretion, decreases serum ferritin levels and reduces liver iron in multi-transfused iron-loaded patients. Toxic side effects were mainly encountered at high doses (80–100 mg/kg/day) and include transient agranulocytosis (5 cases), transient musculoskeletal and joint pains (10–20%), gastric intolerance (2–6%) and zinc deficiency (1%). The incidence of these toxic side effects was reduced by using lower doses of 50–75 mg/kg/day. The overall efficacy and toxicity of L1 is comparable to that of DF in animals and humans. Further work is required for identifying susceptible individuals to L1 toxicity, and also optimum dose protocols of L1 which can maximise iron excretion and minimise the incidence of toxic side effects.     

The value of oxygen index and base excess in predicting the outcome of neonatal acute respiratory distress syndrome

ObjectiveThis study aimed to identify the predictors and threshold of failure in neonatal acute respiratory distress syndrome.MethodsNewborns with severe acute respiratory distress syndrome aged 0–28 days and gestational age ≥36 weeks were included in the study if their cases were managed with non-extra corporal membrane oxygenation treatments. Patients were divided into two groups according to whether they died before discharge. Predictors of non-extra corporal membrane oxygenation treatment failure were sought, and the threshold of predictors was calculated.ResultsA total of 103 patients were included in the study. A total of 77 (74.8%) survived hospitalization and were discharged, whereas 26 (25.2%) died. Receiver operating characteristic analysis of oxygen index, pH, base excess, and combinations of these indicators demonstrated the advantage of the combination of oxygen index and base excess over the others variables regarding their predictive ability. The area under the curve for the combination of oxygen index and base excess was 0.865. When the cut-off values of oxygen index and base excess were 30.0 and ?7.4, respectively, the sensitivity and specificity for predicting death were 77.0% and 84.0%, respectively. The model with base excess added a net reclassification improvement of 0.090 to the model without base excess.ConclusionThe combination of oxygen index and base excess can be used as a predictor of outcomes in neonates receiving non-extra corporal membrane oxygenation treatment for acute respiratory distress syndrome. In neonates with acute respiratory distress syndrome, if oxygen index >30 and base excess <?7.4, non-extra corporal membrane oxygenation therapy is likely to lead to death.