Rapid Responses to:
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Rapid Responses: Rapid Responses published:
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Next Steps
- Brian Morgan (17 January 2003)
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Re: Next Steps
- Malcolm G Coulthard, George B Haycock (5 February 2003)
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Salt intoxication - further considerations
- T L Chambers, M T Bredow (17 February 2003)
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Distinguishing between salt poisoning and hypernatraemic dehydration
- Roy Meadow (14 March 2003)
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Re: Distinguishing between salt poisoning and hypernatraemic dehydration
- Brian Morgan (17 March 2003)
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Distinguishing Between Salt Poisoning and Hypernatraemic Dehydration
- Roy Meadow (18 March 2003)
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What if the wrong diagnosis was made?
- Penny Mellor, DARETOCARE1@aol.com (13 February 2006)
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Time to revisit allegations of salt poisoning?
- Penny Mellor (1 November 2006)
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Brian Morgan, Freelance Journalist Cardiff CF11 6LF
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This article is interesting for a number of reasons I can think of but I will mention three of them and wait to see what else transpires. 1) If the Meadow criteria are the most widely used for the diagnosis of salt poisoning as stated by the authors, and if these criteria have also been accepted as convincing in the criminal and family courts, resulting in convictions or care orders, then this discussion is most welcome. A quick internet search shows that this new paper is the first (on line at least) to examine Meadow's conclusions in the nine years since they were published in Archives of Disease in Childhood. Meadow's criteria emerged from a review of 12 cases. The new study is based on two cases. Readers might agree that there should now be a more methodical review which would lead to increased public confidence in the medical opinions being offered in court in this situation. 2 I personally know the details of one conviction of manslaughter due to salt poisoning based (generally speaking) on the Meadow criteria given in this article. I know that these criteria were fiercely challenged by appropriately qualified medical experts, including an experienced paediatrian, now a professor and by a professor of biochemistry. There are almost certainly bound to be other similar cases. This paper suggests to me that there should be an urgent review of any cases where convictions or care orders were based on salt poisoning criteria similar to the ones highlighted. And 3) I would ask why the 'one in 73 million' likelyhood is cited as having been introduced in a salt poisoning case when so far as is publicly known this was raised only in the Sally Clark murder trial. Was there a second case when this misleading statistic was introduced in court? Competing interests: I may write about this for payment. |
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Malcolm G Coulthard, Consultant paediatric nephrologist Royal Victoria Infirmary, Newcastle NE1 4LP, George B Haycock
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We thank Brian Morgan for his very prompt letter of 17/1/03, commenting on our paper published the next day.[1] He argues that it may be necessary to review all convictions and care orders where children have been found to have been poisoned with salt according to previous criteria. We agree that any cases where the diagnosis was based solely on a high admission urinary sodium concentration should be considered unsafe because this may also be seen in hypernatraemic dehydration, although in most cases the medical details form only part of the evidence. It is important to recognise that at no point in our article did we suggest that deliberate salt poisoning, by parents or others, does not happen. It most certainly does, and the physical consequences alone can be devastating (death or severe brain damage). This makes it all the more important that the diagnosis is made according to sound criteria: a high urinary sodium concentration alone is not enough. The statement that our paper is based on two cases is not strictly correct. It is based on physiological principles, and two cases were cited by way of illustration. The figure that appears in the paper was in fact derived from three cases, two with salt poisoning and one with hypernatraemic dehydration, although unfortunately the legend to the figure did not make this clear. The version originally submitted contained details of other cases but in the interests of space the shorter version finally appeared. Morgan queries why we referred to the issue of “73 million to one” odds [2] in our paper. This is because the argument was used by an advising paediatrician to support a diagnosis of salt poisoning in our case 2 (before it was the subject of a BMJ editorial). 1. Coulthard MG, Haycock GB. Distinguishing between salt poisoning and hypernatraemic dehydration in children. British Medical Journal 2003;326:157-160. 2. Watkins SJ. Conviction by mathematical error? Doctors and lawyers should get probability theory right. British Medical Journal 2000;320:2-3. Competing interests: None declared |
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T L Chambers, Consultant paediatricians Directorate of Children's Services, United Bristol Healthcare Trust, Bristol BS2 8BJ, M T Bredow
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Coulthard and Haycock (1) are to be commended on developing the work of Meadow (2) to clarify further our understanding of the physiological consequences of salt intoxication and its recognition. However we doubt if theirs are the last words on the matter. For example Coulthard and Haycock do not define salt poisoning. Is it an immediate hefty dose, longer term low level administration or is other (forensic) evidence for it needed? On what evidence do they choose fractional excretion rates of sodium >2% and <1% to distinguish salt intoxication from dehydration - and what of the salt intoxicated, dehydrated patient? Furthermore we would remind doctors that the identification of child abuse is not an individual medical endeavour but from the earliest stage requires inter-agency planning and well led and informed team work. Assessment of such complex cases often transcends physiology, renal or otherwise. 1. Coulthard M G, Haycock G B. Distinguishing between salt poisoning and hypernatraemic dehydration in children. BMJ 2003,326,157-160. 2. Meadow R. Non accidental salt poisoning. Archives of Disease in Childhood 1993, 68, 448-452. Competing interests: None declared |
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Roy Meadow, Emeritus Professor Leeds
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Distinguishing Between Salt Poisoning and Hypernatraemic Dehydration Brian Morgan, in his letter of 17.1.03, draws attention to the statement in the history of Case 2 entitled Hypernatraemic Dehydration: "the odds of a second innocent death were suggested (incorrectly) to be 73 million to one". He asks why that likelihood was introduced in this case. The answer, which is not clear from either the response of the authors of 5.2.03, or their published correction of 1.3.03, is that the 73 million to one odds were not used in this case at any stage. The first time that that figure was mentioned, to the recollection of the paediatric experts involved in the case, was at an experts meeting after the BMJ editorial at which one of the experts warned against citing such statistical probabilities. The other experts agreed, and adhered to that in subsequent discussions and in the court hearing itself. Roy Meadow
Competing interests: None declared |
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Brian Morgan, Freelance Journalist Cardiff UK CF11 6LF
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Professor Sir Roy Meadow does not declare in his response to the foregoing what his interest is or involvement was in the case referred to. His response seems incompatible with the situation as described by the original authors, and my concerns remain, to a certain extent, unanswered. It is not wholly clear whether Professor Sir Roy was one of the paediatricians involved in this case, but if he was, I think we should be told, and moreover we should be told when this was. I hope readers will forgive this journalistic search for clarity, which in my opinion is in the public interest. Competing interests: I may use this material in the media and be paid. |
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Roy Meadow, Emeritus Professor Leeds
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Distinguishing Between Salt Poisoning and Hypernatraemic Dehydration Couthard and Heycock used two "illustrative cases" to support their proposal that fractional excretions of sodium and water will distinguish between salt poisoning and dehydration. Case 1 "Salt Poisoning" is a 7 year old who was given excess salt by naso gastric tube. Case 2 is an infant titled "Hypernatraemia Dehydration". It is a pity that the useful paper was spoilt by the misleading distription of Case 2. I was one of several experts involved with that case who had difficulty recognising it from their account. Even the published corrections2 perpetuate the errors. It is as wrong to state that a court hearing "determined that the children had not been salt poisoned"2, as it was in the original article to state that "a court found that the mother was not guilty of manslaughter"1, and it was misleading to omit a mass of important collateral information concerning case 2. In the Family Division of the High Court, the Local Authority, in the course of seeking a Court Order, sought findings that case 2 had incurred non-accidental rib fractures, non-organic failure to thrive, and two episodes of hypernatraemia caused or provoked by the parents' care. In addition, the Local Authority sought findings that two siblings had each incurred non-organic failure to thrive, hypernatraemia caused or provoked by the parents' care, and death as a result of unnatural causes; and that an elder sibling had, in infancy, incurred non-accidental fracture of the femur, and a hypernatraemic episode caused or provoked by the parents care. The parents contested the findings even though the independent paediatric experts commissioned on behalf of the parents, and on behalf of the children's guardian, were not supportive of the parents. The High Court case was expected to last several weeks, but early in the presentation of Local Authority evidence, adjournment was sought and, after discussion with the other parties, the parents' legal team agreed that a Care Order (care and control of case 2 being transferred from the parents) should be granted to the Local Authority. Thereby the detailed evidence was not presented in Court, and no findings of fact were made by the Court. The Judge merely approved the uncontested Care Order. Those familiar with child protection work and the Family Courts have to draw their own conclusions about the likelihood of serious abuse having occurred. The circumstances in which measurement of fractional excretions of sodium and water may identify salt poisoning are worth further study. However, as with most child abuse, there needs to be caution about over- reliance on any one diagnostic test: experience shows the need for consideration of all the factors that result from detailed multi-agency assessment of the child and family. Poisoned children have often incurred previous abuse, as have their siblings6. Secondly, the epidemiology of hypernatraemia needs to be born in mind. Episodes of hypernatraemia occurring iatrogenically to children in hospital on IV drips are common, but apart from the neonatal period and the association of breast feeding and hypernatraemia, it has become progressively less common for ill children to present to hospital with hypernatraemia. Even by 1990 a survey of 1119 children admitted to hospital with gastroenteritis identified only 8 with plasma sodium greater than 149 mmol/L3. More than one bout of hypernatraemia in a child is even more rare, and recurrence of episodes of hypernatraemia in siblings, extraordinarily unusual in children who have been investigated and are known not to have one of the rare endocrine or renal conditions predisposing to hypernatraemia1. Moreover, very high levels of hypernatraemia (e.g. > 170) are very rare in natural disorders. On the other hand, deliberate salt poisoning of children has been found to be recurrent, chronic, and to involve siblings in many families, and often is associated with very high, and dangerous levels, of hypernatraemia4,5,6. When considering the most appropriate pathological test to identify salt poisoning, priority should be given to the collection of a timed sample of urine at the time of hypernatraemia; urine salt output is a reliable indicator of salt intake. That gold standard type of evidence has been used in many cases of salt poisoning, often supplemented with confirmatory evidence from analysis of gastric aspirate or feeding bottles (to which salt has been added). Just because it is difficult to collect a timed3 sample from a young child, should not lead to what will always be second best investigations - reliance on samples in which only concentrations, rather than absolute amounts, are measured. When having to rely on such samples the conventional approach has been to link high urine NaCl concentration alone with salt excess, and low concentration with dehydration7; whether measurement of fractional excretion rates are more reliable in all circumstances remains to be seen. It is clear that fraction excretion of sodium is high when reasonably hydrated children have been given sudden large amounts of salt intravenously or via gastrostomy or nasogastric tubes (e.g. Case 1)1. However, most deliberate salt poisoning occurs in infants and toddlers in whom it has been shown that, unless the child is also deprived of water, it is extremely difficult to persuade the child to ingest large amounts of salt (without vomiting it back), or in sufficient quantity that cause appreciable hypernatraemia unless the child is also deprived of water6 (because given sufficient water the child's kidneys will excrete the excess salt). Thus, even in the early reports it was noted that salt poisoning of infants usually involved both administration of excess salt and deprivation of water4,5. As Chambers and Bredow point out, the usefulness of fractional excretion measurements may be doutbful when salt intoxication and dehydration co-exist. Moreover, for many children the poisoning will have been chronic or repetitive. Paediatricians should continue to aim for the gold standard, seeking to collect a timed sample of urine at the time of unexpected hypernatraemia. A last word of caution concerns the occurrence of hyperglycaemia at the time of hypernatraemia. There have been several cases of salt poisoning where children have been mistakenly treated for diabetes. Hypernatraemia, from different causes, may lead to secondary hyperglycaemia. Roy Meadow
References 1. Coulthard MG, Heycock GP. Distinguishing between salt poisoning and hypernatraemic dehydration in children. BMJ 2003; 326: 157-160. 2. Ibid Correction. BMJ 2003; 326: 497. 3. Conway SP, Phillips RR, Panday S. Admission to hospital with gastroenteritis. Arch Dis Child 1990; 65: 579-584. 4. Feldman KW, Robertson WO. Salt Poisoning: presenting symptoms of child abuse. Vet Hum Toxicol 1979; 21: 341-347. 5. Meadow R. Non-accidental Salt Poisoning. Arch Dis Child 1993; 68: 448-52. 6. Bays J, Feldman KW. Child abuse by poisoning. In: Child Abuse Medical Diagnosis and Management (2nd Edition), Reece RM, Ludwig S. Eds. Lippincott Williams & Wilkins 2001. 7. Beattie TJ. Disturbances in fluid and electrolyte balance. In: Clinical Paediatric Nephrology (2nd Edition), Postlethwaite RJ (ed). Butterworth Heinermann 1994. 8. Chambers TL, Bredow MT. Salt intoxication: further considerations. BMJ Rapid Response 17.2.03. Competing interests: None declared |
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Penny Mellor, Campaigner/researcher Home WV9 5HX, DARETOCARE1@aol.com
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Hypernatraemic dehydration In case 2, a boy born at 28 weeks' gestation with aortic arch and bronchial anomalies needed prolonged ventilation and remained oxygen dependent. Fundoplication was considered because he had severe gastro- oesophageal reflux and was failing to thrive. He was treated with domperidone, a compound alginate preparation (Gaviscon Infant), and feed supplements that contained glucose polymers. The boy's plasma biochemistry was normal, except when he was 5 and 8 months old, when he was acutely ill with high fever, profuse diarrhoea, exacerbation of vomiting, hypotonia, weight loss, and poor perfusion (table). Intravenous fluids dramatically improved his condition and restored his body weight. The boy was taken into foster care after he was admitted at age 8 months, because doctors believed his biochemistry results confirmed salt poisoning and because his siblings' medical histories were considered suspicious. Three siblings had become hypernatraemic under similar circumstances: one died after remaining at home (on the general practitioner's advice) with pyrexia, explosive diarrhoea, and weight loss but without haemorrhagic encephalopathy.3 In addition, one sister, who was eunatraemic, died suddenly and unexpectedly. The odds of a second innocent death were suggested (incorrectly) to be 73 million to one.4 A court found that the mother was not guilty of manslaughter. [1} What if the child had Neuroleptic Malignant Syndrome caused by the Domperidone which is a dopamine 2 antagonist, a class of drugs that are known to cause NMS. [2] NMS is a condition that can cause severe hypernatraemia. [3] The pyrexia and hyperthermia described with nothing to which those findings could be attributed in the paper written by Haycock and Coulthard is consistent with NMS and leaves unanswered questions. Was it even contemplated as a differential diagnosis? [1] http://bmj.bmjjournals.com/cgi/content/full/326/7381/157 [2] http://www.thrombosis- consult.com/articles/Textbook/35_mentation.htm [3] http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12404581&query_hl=4&itool=pubmed_docsum Competing interests: Campaigner against false allegations of child abuse |
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Penny Mellor, Campaigner/researcher Home WV9 5HX
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After much correspondence with the MRHA including supplying them with evidence relating to neuroleptic malignant syndrome (NMS) and Domperidone including evidence of the effect on the brain of Dopamine 2 antagonists when it is underdeveloped or damaged, as well as providing medical data from records of children on Domperidone in which there is unexplained hypernatraemia and hyper-pyrexia -the MRHA have conceded that this now warrants further investigation. I hope that Professors Meadow, Coulthard and Haycock will now take advice from other appropriate experts in order to establsih if indeed their original diagnosis of salt poisoning in case two was wrong. Ms Penny Mellor e-mail: DARETOCARE1@aol.com MHRA Reference: GENQ-00037919 (cross linked to GENQ-00037302) 30th October 2006 Dear Ms Mellor Re: Domperidone Thank you for your response of 17th October 2006 concerning domperidone and for providing a copy of the electronic Yellow Card detailing the fatal case of Neuroleptic Malignant Syndrome in a child. A further search of our database for your Yellow Card with the additional details you provided proved futile as we do not hold a copy of this Yellow Card on our database. The reason behind this is currently unknown. I would like to apologise on behalf of the MHRA and I have been assured that the details of this Yellow Card have now been added to our database. With regards to your concerns relating to domperidone, you may be aware that the following warnings relating to domperidone use in infants is currently within the product information, the Summary of Product Characteristics (SPC) for healthcare professionals: Use in infants: Neurological side effects are rare (see "Undesirable effects" section). Since metabolic functions and the blood-brain barrier are not fully developed in the first months of life the risk of neurological side effects is higher in young children. Therefore, it is recommended that the dose be determined accurately and followed strictly in neonates, infants, toddlers and small children. Overdosing may cause extrapyramidal symptoms in children, but other causes should be taken into consideration. The SPC also contains the following side effects Endocrine disorder: Rare; increased prolactin levels Nervous system disorders: Very rare; extrapyramidal side effects As the hypophysis is outside the blood brain barrier, domperidone may cause an increase in prolactin levels. In rare cases this hyperprolactinaemia may lead to neuro-endocrinological side effects such as galactorrhoea, gynaecomastia and amenorrhoea. Extrapyramidal side effects are very rare in neonates and infants, and exceptional in adults. These side effects reverse spontaneously and completely as soon as the treatment is stopped. The other reactions detailed in the letter by De and Taylor, namely hyperprolactinaemia, galactorrhoea and gynaecomastia, are listed in the SPC as detailed above. Neuroleptic malignant syndrome is not specifically listed. As there are several different brands of domperidone on the UK market it would be helpful to know what brand of domperidone was used by the patient detailed in your Yellow Card. The MHRA will conduct a review to investigate whether domperidone can cause NMS in infants in whom the blood -brain barrier has not fully developed or has been damaged. As part of this review data will be collated from the marketing authorisation holder (MAH) for domperidone according to agreed timelines. In the interim if you consider that additional sources of data should be included within the review please submit these to the Agency. Thank you once again for bringing this issue to our attention and resubmitting a copy of your Yellow Card. Yours sincerely Dr Bridget King
Competing interests: Campaigner against false allegations of child abuse. Was involved in researching R-V-Williams and currently involved in another alleged salt poisoning case involving Domperidone in which the symptoms of NMS are manifest. |
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