Multiple organ failure in a severely malnutrished patient with chromosome aberration
*Roman Kaźmirczuk1, Marlena Jakubczyk2, Sylwia Kołtan3 , Piotr Brzeziński1, Zbigniew Szkulmowski2, Kinga Kupczyk2,4, Piotr Skiba1, Małgorzata Apanasiewicz1, Mariusz Mielniczuk1, Marcin Owczarek1, Mieczysława Czerwionka-Szaflarska4, Mariusz Wysocki3, Krzysztof Kusza2
1Department of Paediatric Anaesthesiology and Intensive Therapy, Collegium Medicum, UMK in Bydgoszcz,
2Department of Anaesthesiology and Intensive Therapy, Collegium Medicum, UMK in Bydgoszcz
3Department of Paediatrics, Haematology and Oncology, Collegium Medicum, UMK in Bydgoszcz
4Department of Paediatrics, Allergology and Gastroenterology, Collegium Medicum, UMK in Bydgoszcz
Background. Pneumonia and malnutrition are two of the biggest killers in childhood, as defined by the World Health Organisation. Although common in the developing world, these conditions can also be observed in more advanced countries, as a result of negligence and lack of proper care in disabled children. We describe a case in which severe malnutrition resulted in multiple organ failure.
Case report. A 16-yr-old retarded girl with +14q chromosome aberration, was admitted to hospital because of severe anaemia and dyspnea. She was extremely malnourished. Her body weight was 32 kg with a height of 152 cm (BMI 13.9). Her Hb concentration was 1.12 mmol L-1, Ht 7%, and RBC 0.93 T L-1. RBC transfusion resulted in transfusion-related acute lung injury (TRALI) and multiple organ failure. She was treated with mechanical ventilation, inotropic support and parenteral nutrition, complicated by the refeeding syndrome and gastrointestinal haemorrhage. After recovery, a gastrostomy was performed, but due to gastric retention she required a laparotomy for adhesiolysis. The girl recovered and remains under home care.
Discussion. In a case of a girl with retardation, multiple organ failure resulting from ten years of malnutrition was observed. She was especially difficult to treat because of a prolonged dysfunction of homeostasis, hypoproteinemia, hypophosphatemia and SIRS. Such patients require careful treatment in ICU settings.
Malnutrition in children and adolescents is nowadays one of the key health problems in the world. Reports of malnutrition concern mainly developing countries. It is estimated that half of paediatric deaths worldwide is caused, directly or indirectly, by malnutrition. Most undernourished and emaciated children come from Africa, South America and Asia [1, 2]. Malnutrition in children, similarly to adults, can develop as a complication of chronic diseases or result from insufficient supply of nutrients.
In recent years, increased attention has been paid to the problem of malnutrition in hospitals . It is worth considering whether this is not due to improper basic medical care and lack of education in this respect. Prophylactic screenings of children and adolescents are conducted 11 times: 6 times during the first year of life, 5 – in subsequent years (at the age of 2, 4, 6, in the second grade of primary school and in the secondary school). The real problem concerns those children who do not attend kindergartens or schools and do not have an individual curriculum and education plan. This regards mainly children with CNS and genetic diseases. The chronic nature of an ailment, difficult feeding caused by dysphagia, oesophagitis, gastroesophageal reflux and poor parental care as well as lack of help on the part of community services lead to malnutrition and deprive children of proper multi-specialist care .
The paper presents a case of malnutrition causing multiple organ failure in a patient with genetic aberrations.
A 16-year-old female diagnosed with +14q chromosome aberration was admitted to the hospital due to dyspnoea and severe anaemia. Medical history revealed that during the first five years of her life, the girl suffered from retardation but was able to move unaided. She was frequently hospitalized due to recurrent pneumonia. On admission, the patient`s general condition was severe; she was dyspnoeic at rest, undernourished, pale, and had numerous bone deformities. Laboratory tests showed: Hb 1.12 mmol L-1, RBC 0.93 T L-1, Ht 7%, MCV 75.3 fL, WBC 5.29 G L-1, PLT 232 G L-1. Moreover, decreased concentration of folic acid was observed (6.57 mol L-1; ref. range 14-34 mol L-1) with normal B12 concentration. Haemolysis was excluded. The level of CRP was slightly elevated (14.33 mg L-1), and the LDH activity was 266 U L-1.
The treatment involved infusion fluids and irradiated leukoreduced red blood cells (ILRBCs). During subsequent 3-6 h of hospitalization, following the ILRBC transfusion, the child developed rapidly increasing respiratory-circulatory failure that required ITU treatment. On admission to ITU, the child’s general state was found severe. She was unconscious, had pale skin with delayed capillary return, and cold extremities. The examination revealed hypoxemia, hypercapnia, tachycardia, decreased SAP to 70 mm Hg, numerous rales as well as crecipitations over the lung fields, distended abdomen, spleen protruding approximately 4 cm from under the coastal arch. Her body weight was 32 kg and height – 152 cm (Table 1). Laboratory test results disclosed anaemia (RBC 2.18 T L-1, Hb 3.4 mmol L-1) at normal platelet and leukocyte count, decreased albumin concentration (29 g L-1), increased concentration of CRP (18.4 mg L-1) and of transaminases (AlAT – 126 U L-1, AspAT – 226 U L-1), LDH 461 U L-1. Chest X-ray showed complete
shadowing of the left lung, parenchymal lesions in the right lung spreading outward from the hili as well as numerous bone deformities. The picture was suggestive of massive pulmonary oedema. The ultrasound scan of the heart revealed right atrial and ventricular hypertrophy and poor left ventricular contractility.
Artificial lung ventilation, catecholamines, antibiotics, proton pump inhibitors and parenteral nutrition were instituted. Despite gradually introduced parenteral nutrition, symptoms of refeeding syndrome were observed on day 3 and 4 (significant hypophosphataemia – 0.39 mmol L-1, slightly reduced potassium and calcium).
During the successive days of hospitalization parameters of inflammation increased (CRP to 240 mg L-1); the patient developed thrombocytopaenia (44 G L-1) and leukopaenia (0.67 G L-1). Although the clinical picture and laboratory results were indicative of septic nature of the disease, microbiological cultures were negative. On day 10, due to sudden gastrointestinal haemorrhage, endoscopy of the upper alimentary tract was performed, which showed features of chronic gastritis and oesophagitis with numerous bleeding erosions.
After the treatment, the results of laboratory tests normalized. On day 21, the patient was extubated. On day 22, the girl in generally good condition was transferred to the referring ward, where hematologic causes of anaemia were excluded. Due to respiratory failure caused by ILRBC transfusion, tests for post-transfusion reaction were carried out. MAIPA performed using monoclonal anti-GP antibodies and ELISA showed anti-HLA class I and II antibodies. However, the presence of these antibodies was not confirmed by the serologic test. Due to dysphagia, in order to introduce intragastric feeding, percutaneous endoscopic gastrostomy (PEG) was performed. Nevertheless, gastric retention was observed, which could suggest bowel obstruction. A laparotomy for adhesiolysis was required. Intragastric feeding was gradually introduced and was well tolerated. Currently, the girl remains under the care of the Clinic for Home Parenteral and Enteral Nutrition; her body weight is 35 kg and haemoglobin concentration – 8.3 mmol
Malnutrition, regardless of its type (marasmus, kwashiorkor, mixed) depends on a child’s ability to adapt to the deficient diet. Prolonged malnutrition impairs anabolic processes of synthesis of “secondary” importance substances and augments catabolic processes to obtain building and energy substrates from endogenic sources to maintain vital functions [5, 6]. Initially, glucose metabolism in the liver slows down by approximately 50%. Stress hunger increases the production of catecholamines, which intensify lipolysis, glycolysis, gluconeogenesis and ketogenesis inducing hyperglycaemia. Subsequently, basal metabolism drops by 30%, insulin secretion decreases and dysfunction of the immune system develops due to atrophy of the lymphatic tissue [6, 7].
The consequences of malnutrition are particularly dangerous for children, since belated nutritional therapy may irreversibly impair their growth and development [8, 9]. Our patient was earlier diagnosed with chromosome aberration, which is a progressing disease; therefore, it is difficult to determine exactly to what extent the unbalanced and deficient diet influenced her development.
On admission, the patient was diagnosed with severe anaemia, which caused dyspnoea. Only a few reports on severe anaemia resulting from malnutrition are available and these pertain mainly to younger children on milk diet . Moreover, anaemia (Hb 1.3 mmol L-1) was diagnosed and described in a 6-year-old girl with hiatus hernia .
In the differential diagnosis of multiorgan failure observed in our patient, the following two pathomechanisms were considered: transfusion-related acute lung injury (TRALI) since her condition deteriorated after ILRBCs and refeeding syndrome (RS).
The incidence of TRALI is estimated at 1:2000 to 1:7000 of transfused blood units [12, 13]. To date, 300 cases have been described, including 4 in Poland. In only one of these 4 cases, antibodies characteristic of this syndrome were detected; the remaining 3 cases were diagnosed based on the clinical symptoms [14, 15]. The following antibodies are involved in the TRALI pathogenesis: anti-HLA, anti-HNA granulocyte-specific alloantibodies, and those reacting with immunoglobulin class A, i.e. anti-IgA2m. In 5-15% of TRALI cases, no antibodies are detected. The antibodies cause granulocyte agglutination in the lungs leading to microembolism, activate the complement and additionally induce the activation and aggregation of granulocytes, their outward shift and sequestration in the pulmonary circulation. Simultaneously, activation of proteases and damage to the endothelium, whose permeability increases, are observed [12, 13].
Clinically, TRALI syndrome manifests with dyspnoea, which occurs 1-6 h after transfusion and is accompanied by hypoxia, tachycardia, hypo- or hypertension. In subsequent hours pulmonary oedema develops. The X-ray picture shows bilateral interstitial infiltrations often of the “butterfly” shape [12, 13].
Our patient developed the symptoms 3 h after ILRBC transfusion. The clinical picture and X-ray findings were characteristic of TRALI. Moreover, using the immunoenzymatic and enzymatic methods, anti-HLA class I and II antibodies were detected. FLOW PRA was seronegative (for TRALI).
The refeeding syndrome develops in prostrated patients and is caused by insufficient adaptive mechanisms in response to increased food supply. Initially, mainly due to increased carbohydrate supply, feeding leads to hyperglycemia and increased insulin secretion, which causes the shift of phosphorus and other macro- and microelements from the extracellular to the intracellular space. In the latter, phosphorus is used in the production of ATP molecules [16, 17, 18]. Additionally, due to the increased protein supply, phosphorus and other mineral compounds (mainly calcium, magnesium, potassium) as well as vitamins (mostly vitamin B1 involved in the Krebs cycle) are used for tissue regeneration, synthesis of phospholipids in newly formed cells and phosphorylation of intermediate metabolites for synthesis of proteins and production of glycogen. Due to reduced concentration of inorganic phosphorus, serum ATP levels decrease and cellular respiration becomes impaired [16, 18], which leads to cardiovascular disturbances, initially tachycardia, followed by bradycardia, conduction blocks, decreased cardiac output and myocardial failure. Muscle hypoxia may lead to massive rhabdomyolysis, embolism, multiorgan failure, starting with renal failure [16, 17, 18]. The most frequent neurological disorders accompanying this syndrome include: paresthesias, seizures and coma. In our case, such disorders were not observed, since the patient was administered sedation necessary for mechanical lung ventilation.
Hypophosphataemia during intensive nutritional therapy was first observed in Japanese soldiers in 1940; first reports, however, were published only in 1951 . In 1946, the study was published concerning cardio-neurological disorders resulting from prolonged malnutrition in Warsaw Ghetto inhabitants . Since the 70ties, the syndrome has been frequently described as a complication resulting from intensive nutritional therapy, especially parenteral. There are only a few Polish reports concerning this syndrome (mainly review articles).
In the case described, the patient developed generalized inflammatory reaction with exacerbation of chronic gastritis and oesophagitis, gastrointestinal bleeding and mechanical ileus requiring surgical intervention. All disturbances, however, were primarily caused by severe prolonged malnutrition.
Severe malnutrition in children and adolescents may become the key etiological factor responsible for multiorgan failure syndrome.
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