Scientific letter
Refeeding syndrome: What to expect when you’re not expecting
Síndrome de realimentación: qué esperar cuando no estás esperando
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On admission, a prognosis score showed no severity criteria (Glasgow score 7 points [poor prognosis if score<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>9 points], Maddrey 9 points [poor prognosis if score<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>32 points] and MELDNa<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>13 points [90-day mortality<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>2% if score<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>17 points]) and the electrolyte values were normal. She was started on fluid therapy, oral thiamine supplementation (100<span class="elsevierStyleHsp" style=""></span>mg/day) and prophylaxis of withdrawal syndrome with oxazepam (15<span class="elsevierStyleHsp" style=""></span>mg every 8<span class="elsevierStyleHsp" style=""></span>h). A mini nutritional assessment score evidenced the presence of malnutrition (score of 10 points [malnutrition if<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>17 points]), confirmed as severe malnutrition, according to GLIM criteria (body mass index [BMI] of 14.5<span class="elsevierStyleHsp" style=""></span>kg/m<span class="elsevierStyleSup">2</span> [weight 39.4<span class="elsevierStyleHsp" style=""></span>kg; height 165<span class="elsevierStyleHsp" style=""></span>cm] and reduced food intake).<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">1</span></a> In this context, oral nutritional supplementation (520<span class="elsevierStyleHsp" style=""></span>kcal) was initiated on day 4 in the ward, in addition to the hospital culinary diet, adding up to a total daily intake of 2620<span class="elsevierStyleHsp" style=""></span>kcal (66<span class="elsevierStyleHsp" style=""></span>kcal/kg/day). The day after, the patient developed gait ataxia, dysarthria and nystagmus, suggestive of Wernicke's encephalopathy, cerebrovascular event excluded. Intravenous supplementation of thiamine was started (500<span class="elsevierStyleHsp" style=""></span>mg every 8<span class="elsevierStyleHsp" style=""></span>h), and the nutritional plan maintained. However, in the following hours, the patient developed shock and ventilatory failure, requiring aminergic support and invasive mechanical ventilation. The study highlighted severe hypophosphataemia (0.07<span class="elsevierStyleHsp" style=""></span>mmol/l [0.87–1.45]), hypomagnesaemia (0.53<span class="elsevierStyleHsp" style=""></span>mmol/l [0.60–1.10]) and hypokalaemia (2.6<span class="elsevierStyleHsp" style=""></span>mmol/l [3.5–5.0]), without worsening cytocholestasis or coagulopathy. Other causes of shock, such as infection, pulmonary thromboembolism or acute coronary event were excluded. A transthoracic echocardiogram showed signs of stress cardiomyopathy. This clinical presentation was assumed in the context of refeeding syndrome and Wernicke's encephalopathy, and electrolyte replacement and organ dysfunction support were started in an intensive care unit. The electrolytes normalised and feeding was restarted at a slower rate, starting at 600<span class="elsevierStyleHsp" style=""></span>kcal per day (15<span class="elsevierStyleHsp" style=""></span>kcal/kg/day). The patient gradually improved, allowing for the suspension of aminergic and ventilatory support, with progressive resolution of the remaining condition, so she was transferred to a general ward. A progressive improvement in functional status was observed after reinforcement of motor rehabilitation, allowing her to be discharged one month after admission, under oxazepam, thiamine, pyridoxine and folic acid supplementation. She was advised to maintain a culinary diet, without enteral supplementation and to maintain alcohol abstinence. At the time of discharge, she presented a BMI of 14.5<span class="elsevierStyleHsp" style=""></span>kg/m<span class="elsevierStyleSup">2</span> (weight 39<span class="elsevierStyleHsp" style=""></span>kg), with no neurological symptoms or signs, electrolyte or liver profile disorders. Two months later she had completely recovered her functional status, presenting a BMI of 15<span class="elsevierStyleHsp" style=""></span>kg/m<span class="elsevierStyleSup">2</span> (weight 41<span class="elsevierStyleHsp" style=""></span>kg) and a daily caloric intake of 1100<span class="elsevierStyleHsp" style=""></span>kcal (27<span class="elsevierStyleHsp" style=""></span>kcal/kg/day), with an alcohol consumption of 10<span class="elsevierStyleHsp" style=""></span>g per day, and she was motivated to maintain a progressive weight increase.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Malnutrition is directly associated with the ability to respond to disease, leading to potential medical and surgical complications, extended hospitalisation and higher healthcare costs.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">2</span></a> Therefore, nutrition screening tools have been widely adopted in order to quickly identify and intervene in patients at higher nutritional risk.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">2</span></a> However, vigorous oral, enteral or parenteral refeeding in malnourished patients can be fatal.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">3–5</span></a> Refeeding syndrome is a rare and potentially fatal condition, caused by the shift in fluids and electrolytes that may occur after the reintroduction of feeding in malnourished patients.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">3,4</span></a> Elderly people and alcoholic, oncologic and anorexic patients are the major risk groups in developed countries.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">5</span></a> The underlying mechanism of this condition rests on the rise of insulin levels caused by refeeding, promoting cellular glucose and phosphorus uptake for the production of phosphorylated compounds.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">6</span></a> This leads to a sharp decline in phosphorus levels, already depleted in malnourished patients, making hypophosphataemia the hallmark characteristic of this syndrome.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">6</span></a> It may also feature hypokalaemia, hypomagnesaemia and thiamine deficiency, due to underlying malnutrition and consumption of reserves during the carbohydrate metabolism, that begins with refeeding.<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">6,7</span></a> This results in multiple system disorders, including cardiovascular (myocardial contractility impairment and arrhythmias), respiratory (diaphragm contractility impairment and ventilatory failure), gastrointestinal (liver cytolysis), muscular (muscle weakness and rhabdomyolysis) and neurological manifestations (tremors, delirium, seizures or Wernicke's encephalopathy due to thiamine deficit, even in the absence of alcoholism).<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">7,8</span></a> The absence of diagnostic criteria makes it difficult to get accurate data on incidence rates.<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">7,9</span></a> However, considering the high prevalence of hospital malnutrition (approximately 30%), it is essential to be aware of this condition, which is preventable and remains relatively unknown in the medical community.<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">4,10</span></a> The aggressive refeeding of this malnourished woman, highly stimulating anabolism, resulted in severe metabolic changes that led to multi-organ failure with cardiogenic shock, ventilatory failure and Wernicke's encephalopathy. This extreme disorder, although rare, reinforces the importance of identifying the patients at risk (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">11</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">In cases like this, it is essential to verify hydro-electrolytic status before initiating refeeding, with electrolyte and vitamin replacement, if necessary, in order to avoid the development of this syndrome.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">3</span></a> According to international guidelines, refeeding should only start after electrolyte replacement and at a slow rate, starting with a maximum caloric intake of 10<span class="elsevierStyleHsp" style=""></span>kcal/kg/day, which corresponds to 16% of the provided intake in this case.<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">9,11,12</span></a> Moreover, a caloric intake of only 5<span class="elsevierStyleHsp" style=""></span>kcal/kg/day should be considered in extreme cases (for example, BMI less than 14<span class="elsevierStyleHsp" style=""></span>kg/m<span class="elsevierStyleSup">2</span> or negligible intake for more than 15 days).<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">11</span></a> Additional increments should be made gradually, over three to seven days, until the target rate is reached.<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">11,12</span></a> Volume replacement should also be cautious, since these patients frequently have impaired cardiac and renal reserve with decreased ability to excrete an excessive volume load.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">11</span></a> In the first 10 days, patients should also receive oral thiamine 200–300<span class="elsevierStyleHsp" style=""></span>mg per day, vitamin B compound tablets three times a day and a trace element supplement once a day.<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">11,12</span></a> In terms of surveillance, daily monitoring of renal function, blood glucose and electrolytes, especially phosphorus and magnesium, is essential, the levels of which should be stabilised before the start of refeeding.<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">11,12</span></a> In conclusion, this case illustrates the vulnerability of malnourished patients to refeeding syndrome. Although it is necessary to recognise and treat malnutrition, the process of refeeding should be cautious. Measures should be taken to identify the risk of refeeding syndrome and prevent this potentially fatal condition.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflict of interest</span><p id="par0020" class="elsevierStylePara elsevierViewall">The authors do not declare any conflicts of interest in relation to the work described.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflict of interest" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">One or more of the following:</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Body mass index<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>16<span class="elsevierStyleHsp" style=""></span>kg/m<span class="elsevierStyleSup">2</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Unintentional weight loss<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>15% in the past three to six months \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Little or no nutritional intake for >10 days \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Low levels of potassium, phosphate or magnesium before feeding \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Two or more of the following:</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Body mass index<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>18.5<span class="elsevierStyleHsp" style=""></span>kg/m<span class="elsevierStyleSup">2</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Unintentional weight loss<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>10% in the past three to six months \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Little or no nutritional intake for<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>5 days \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>History of alcohol abuse or drugs, including insulin, chemotherapy, antacids or diuretics \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3333483.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Criteria for identifying patients at high risk of refeeding problems.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">11</span></a></p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:12 [ 0 => array:3 [ "identificador" => "bib0065" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "GLIM criteria for the diagnosis of malnutrition – a consensus report from the global clinical nutrition community" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "T. 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