Review
Hypocalcaemia, hyperkalaemia and massive haemorrhage in liver transplantation
Hipocalcemia, hiperpotasemia y hemorragia masiva en el trasplante de hígado
a MD, Adjunct Professor, Anaesthesiology Service, Bi-Institutional Liver Transplant and UDA, National Hepato-Bilio-Pancreatic Centre, Biomedical Engineering Unit, Military Hospital, Medical and Engineering Schools, Universidad de la República, Montevideo, Uruguay
b MD, Hemotherapy Service and Bi-Institutional Liver Transplant Unit, Military Hospital, Uruguay
c MD, Assistant Professor, Anaesthesiology Service, Bi-Institution Liver Transplant Unit, Hospital de Clínicas, Universidad de la República, Montevideo, Uruguay
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This gives rise to complex alterations of the internal milieu that may result in life-threatening intraoperative events. Immediate identification and anticipation of these disorders is a mainstay in anaesthetic management. The objective of this review is to provide an overview of the mechanisms and treatment of the most frequent serum calcium and potassium abnormalities occurring as a result of using large volumes of blood products for replacement. Particular details on citrate intoxication, hypocalcaemia and hyperkalaemia will be provided in the context of acute massive haemorrhage during liver transplant surgery.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Methodology</span><p id="par0010" class="elsevierStylePara elsevierViewall">Non-systematic review of the literature was conducted in the MEDLINE, OVID and Cochrane databases using words such as: “hypocalcaemia”, “hyperkalaemia”, “massive transfusion”, “acidosis” and “liver transplantation”. Relevant articles and associated references that help understand the aetiology, diagnosis and treatment of calcium and potassium disorders during massive haemorrhage were selected. Relevant articles for the interpretation of those disorders during liver transplant surgery were also included.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Massive haemorrhage</span><p id="par0015" class="elsevierStylePara elsevierViewall">Massive haemorrhage is one of the main causes of death and intraoperative cardiac arrest in adults as well as children.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1–4</span></a> It is usually defined in relation to the volume of blood products transfused over 24<span class="elsevierStyleHsp" style=""></span>h by kilograms of body weight: 10 volumes of red blood cells (RBCs) in a patient weighing 60<span class="elsevierStyleHsp" style=""></span>kg,<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> replacement of more than 50% of the blood volume in 3<span class="elsevierStyleHsp" style=""></span>h, or transfusion of more than 4 volumes of RBCs in 1<span class="elsevierStyleHsp" style=""></span>h.</p><p id="par0020" class="elsevierStylePara elsevierViewall">However, in cases of acute haemorrhage happening within a period of minutes, immediate identification is required in order not to delay therapeutic action. For that reason, in anaesthesia we prefer to consider millilitres of blood lost in a few minutes: 150<span class="elsevierStyleHsp" style=""></span>ml/min or more than 1.5<span class="elsevierStyleHsp" style=""></span>ml/kg/min over a period of more than 20<span class="elsevierStyleHsp" style=""></span>min.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Mortality is associated with the presence of acidosis (pH<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>7.1), hypothermia, coagulopathy, number of concentrated blood products transfused and volume ratios between the different blood products given.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> The acute complications of massive haemorrhage are related with shock and transfusion therapy.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8,9</span></a> We will focus on two of these, namely, citrate toxicity<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7,10,11</span></a> and hyperkalaemia.<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,7,12</span></a> Hypomagnesaemia is another frequent ionic abnormality in patients with massive haemorrhage, although it does not seem to be significantly associated with mortality.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a></p><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Hypocalcaemia</span><p id="par0025" class="elsevierStylePara elsevierViewall">Although it is defined as a total serum calcium concentration of less than 8.5<span class="elsevierStyleHsp" style=""></span>mg/dl (4.5<span class="elsevierStyleHsp" style=""></span>mEq/l, 2.10<span class="elsevierStyleHsp" style=""></span>mmol/L),<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> clinical hypocalcaemia may occur even with normal total calcium values when serum ionized calcium concentrations are lower than 4.5<span class="elsevierStyleHsp" style=""></span>mg/dl. In surgery, the most common causes of hypocalcaemia are hyperventilation and citrated blood infusion at a rate of more than 1.5<span class="elsevierStyleHsp" style=""></span>ml/kg/min. Acute respiratory alkalosis reduces ionized calcium by lowering hydrogen ion concentrations, freeing albumin binding sites and leading to increased ionized calcium protein binding. The clinical manifestations of hypocalcaemia are due to the lowering of ionized calcium, because it is this free fraction which acts on membrane potentials.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> That is why it manifests in excitable tissues: changes in mental status (central nervous system), tetany (skeletal muscles), hypotension (smooth muscle) and arrhythmias, prolonged QT interval or pulseless electrical activity (myocardium).<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9,14</span></a> Plasma calcium levels are a poor surrogate indicator for total body calcium, accounting for only 0.1–0.2% of the extracellular calcium and 1% of total body calcium. Ionized calcium, in turn, usually represents 40–50% of plasma calcium. Total serum calcium concentrations must be interpreted in relation to serum albumin. In the presence of hypoalbuminemia, there is less substrate for calcium binding, allowing for a larger percentage of free calcium, ionized calcium. In this situation, plasma calcium values may underestimate ionized calcium values.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> Serum calcium concentrations are corrected in relation to a concentration of albumin of 40<span class="elsevierStyleHsp" style=""></span>g/L; for every 1<span class="elsevierStyleHsp" style=""></span>g/L of albumin above or below this value, calcium is adjusted by lowering or increasing it by 0.02<span class="elsevierStyleHsp" style=""></span>mmol/L. This estimate may not be accurate in critically ill patients.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> The use of 5% albumin and of blood products during liver transplant determines protein binding of calcium ions.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> On the other hand, in critically ill inpatients with hypoalbuminemia there may be a lower value of total calcium without lowering of ionized calcium.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> In these cases, there is no need for acute calcaemia correction, but improving nutrition is required.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">During blood transfusion, the degree of hypocalcaemia depends of the patient's volemia, the volume of blood products administered, the transfusion rate, and liver function.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Hypocalcaemia during massive haemorrhage is a predictor for mortality, and there is a linear relationship between calcaemia values and mortality. Lower plasma calcium is a better indicator of hospital mortality than minimum fribrinogen concentration, acidosis or low platelet counts.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a></p><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Citrate intoxication</span><p id="par0040" class="elsevierStylePara elsevierViewall">It manifests as signs of hypocalcaemia.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> Stored blood is anticoagulated using citrate (3<span class="elsevierStyleHsp" style=""></span>g/unit of RBC), which chelates calcium. In a healthy adult, the liver metabolizes 3<span class="elsevierStyleHsp" style=""></span>g of citrate in 5<span class="elsevierStyleHsp" style=""></span>min. Infusion rates greater than 1 unit of RBC/5<span class="elsevierStyleHsp" style=""></span>min, or liver dysfunction, drive citrate elevation and lower plasma ionized calcium.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> When circulating volume is well maintained, cardiovascular manifestations occur with infusion rates of 150<span class="elsevierStyleHsp" style=""></span>ml/70<span class="elsevierStyleHsp" style=""></span>kg/min of citrated blood. However, when there is hypothermia of 31<span class="elsevierStyleHsp" style=""></span>°C, citrate metabolism rates drop by 50% and toxicity may occur with slower infusion rates. With the new preservatives (lower citrate content), intoxication is less probable.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> A similar situation occurs when sodium bicarbonate (HCO<span class="elsevierStyleInf">3</span>) is infused at a fast rate; free calcium binds to HCO<span class="elsevierStyleInf">3</span>, lowering the percentage of ionized calcium.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> In low-flow states (cardiac arrest or haemodynamic arrest with electrical activity) there is ionized calcium lowering<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> independent from total concentration. The mechanism is a disrupted distribution of free calcium. Consequently, if citrate-containing blood is administered to a patient with tissue hypoperfusion, ionized calcium reduction will be greater than in stable situations. It is important to improve the patient's haemodynamic state in order to mobilize ionized calcium from body stores. Paradoxically, blood administration may improve plasma levels of ionized calcium as it improves circulatory status. Acidosis and the total volume of transfused fresh plasma are associated with severe hypocalcaemia in patients with massive bleeding.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Neonates are at risk of developing heart failure due to hypocalcaemia during transfusion, because cardiac function (relaxation and contraction) depends largely on plasma concentrations of ionized calcium.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> When neonates present liver failure leading to lower citrate metabolism and the risk is very high, death may ensue.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Citrate toxicity may be prevented in these cases if the transfusion rate is kept below 1<span class="elsevierStyleHsp" style=""></span>ml/kg/min<span class="elsevierStyleSup">2</span>.</p><p id="par0050" class="elsevierStylePara elsevierViewall">During liver transplantation, hypocalcaemia is multifactorial<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15,23</span></a>: transfusions, diminished metabolic capacity of the liver,<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> and reduced liver blood flow. As a result, there is a need to infuse high calcium doses during liver transplantation (1<span class="elsevierStyleHsp" style=""></span>g/h of calcium gluconate).<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Treatment of hypocalcaemia: calcium gluconate and calcium chloride</span><p id="par0055" class="elsevierStylePara elsevierViewall">Intravenous calcium administration is the appropriate treatment for acute or severe hypocalcaemia, using 10% calcium chloride (1.36<span class="elsevierStyleHsp" style=""></span>mEq/l) or calcium gluconate (0.45<span class="elsevierStyleHsp" style=""></span>mEq/l). The former provides 3 times as much calcium than an equal volume of 10% calcium gluconate, because chloride molecular mass is 147 compared to the molecular mass of gluconate of 448.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the chemical differences between calcium chloride and calcium gluconate. If an equivalent dose of calcium is administered in either of the two formulations,<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> the therapeutic response is similar, there being no significant differences between the dissociation rates for both compounds.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> The two preparations may be used with similar efficacy for the treatment of intraoperative hypocalcaemia.<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26,27</span></a> Calcium gluconate is the preferred form for intravenous use, given that calcium chloride tends to cause local irritation when used through a peripheral line, and has to be administered through a central venous line.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> In the event there are signs of hyperkalaemia or hypocalcaemia, a bolus administration is required under mandatory electrocardiographic monitoring, due to the risk of arrhythmias.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> The recommended dose for treating intraoperative hypocalcaemia in case of bleeding requiring blood product transfusions is 5–10<span class="elsevierStyleHsp" style=""></span>mg/kg of calcium chloride or 15–30<span class="elsevierStyleHsp" style=""></span>mg/kg of calcium gluconate, the requirement in children and neonates being higher.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> This usually results in transient improvement (considering that the two preparations have a short half-life) and there is a need for continuous calcium administration to prevent recurrent hypocalcaemia and dangerous fluctuations of plasma levels.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17,29</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Hyperkalaemia</span><p id="par0060" class="elsevierStylePara elsevierViewall">It is defined as a serum potassium level greater than 5.5<span class="elsevierStyleHsp" style=""></span>mEq/l. It is usually considered mild up to 6<span class="elsevierStyleHsp" style=""></span>mEq/l, moderate between 6 and 7<span class="elsevierStyleHsp" style=""></span>mEq/l, and severe when greater than 7<span class="elsevierStyleHsp" style=""></span>mEq/l. It may be caused by external or internal balance disruptions.<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">30,31</span></a> The most frequent causes include severe renal failure, iatrogenic injury, the use of angiotensin converting enzyme (ACE) inhibitors<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> and bank blood transfusions.<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,33</span></a> In anaesthesia and surgery, perfusion of an extensive, previously ischaemic vascular bed triggers the release into the circulation of large quantities of potassium resulting from the outflow of intracellular potassium, due to disrupted membrane pumps from local acidosis. In liver transplant, the perfusion of the recently placed graft (ischaemic and preserved in a solution with a high potassium content) gives rise to sharp increases of plasma potassium that may provoke the death of the patient.<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">34,35</span></a></p><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Hyperkalaemia and acidosis</span><p id="par0065" class="elsevierStylePara elsevierViewall">Acidosis increases plasma potassium concentrations by inducing outflow from the cell into the extracellular compartment through hydrogen exchange (altered internal balance).<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a> In the kidney, H<span class="elsevierStyleSup">+</span> increases result in reduced tubular potassium secretion, disrupting the external balance as well.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Hyperkalaemia and blood transfusion</span><p id="par0070" class="elsevierStylePara elsevierViewall">Rapid RBC transfusion may result in cardiac arrest.<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,33</span></a> Plasma potassium concentration increases in stored blood in a manner directly proportional to storage time (0.5 and 1<span class="elsevierStyleHsp" style=""></span>mEq/l per day), reaching values of up to 7–77<span class="elsevierStyleHsp" style=""></span>mEq/l in RBCs.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> The mechanism is potassium outflow from red blood cells due to Na<span class="elsevierStyleSup">2+−</span>K-ATPase membrane pump as a result of the lack of ATP. Moreover, RBCs contain a CPD (citrate-phosphate-dextrose) or CPDA (citrate-phosphate-dextrose-adenine) solution with a pH of 5.5, which lowers the pH from 7.0 down to 6.6 after 21–35 days of storage. The result is an accumulation of potassium, fixed acids and CO<span class="elsevierStyleInf">2</span> that may produce myocardial depression when infused in the context of massive bleeding.<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a> Potassium concentrations in RBC units increase with radiation and diminish with red blood cell washing.<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a> Rapid transfusion through a central venous catheter may deliver higher potassium concentrations into the coronary circulation than when given through a peripheral venous line, and this may contribute to the risk of cardiac arrest.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9,37</span></a> Moreover, some pressurized infusion devices may traumatize red blood cells, giving rise to greater potassium outflows from the cell.<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a> The new rapid infusion and fluid warming devices do not produce significant cell destruction. The volume of blood products infused per minute appears to be the main factor associated with hyperkalaemia-related arrest in children, the use of peripheral venous catheters being preferred over central lines in the event there is a need for rapid replacement.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Hyperkalaemia in liver transplant</span><p id="par0075" class="elsevierStylePara elsevierViewall">Elevated preoperative plasma potassium concentration is the most important predictor for hyperkalaemia during surgery.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> Other factors include the presence of acidosis, osmolarity, insulin and catecholamine treatment, red blood cell transfusion, and the presence of renal failure.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">Controlling plasma potassium values before graft perfusion during liver transplant is a fundamental pillar in preventing intraoperative cardiac arrest. Cardiovascular collapse may be due to many causes hypothermia, acidosis, hypocalcaemia, and pulmonary embolism,<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a> hyperkalaemia being a frequent, avoidable cause.<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">41,42</span></a></p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Clinical manifestations</span><p id="par0085" class="elsevierStylePara elsevierViewall">Plasma potassium changes drive changes in cell membrane electric potential at rest, which manifest in the form of muscle weakness or paralysis, and cardiac conduction or repolarization abnormalities. The earliest most typical electrographic sign is an altered, more pronounced, T wave. This abnormality may progress to a prolonged PR interval, widening of the QRS complex, ventricular fibrillation and asystole after 7<span class="elsevierStyleHsp" style=""></span>mEq/l.<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">37,43</span></a> Treatment includes electric stabilization of the heart, potassium redistribution from plasma into the cells, and potassium clearance from the body.<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">44</span></a> Dialysis removes 50–80<span class="elsevierStyleHsp" style=""></span>mEq/l of potassium in 4<span class="elsevierStyleHsp" style=""></span>h and may be used in exceptional cases such as patients with severe renal insufficiency or in simultaneous liver and kidney transplantation.<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">45</span></a></p></span></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Conclusions</span><p id="par0090" class="elsevierStylePara elsevierViewall">The concomitant presence of bleeding, ionic abnormalities and cardiac complications in the context of liver transplant surgery are frequent and potentially lethal.</p><p id="par0095" class="elsevierStylePara elsevierViewall">Liver transplant patients often have one or several risk factors for developing intraoperative cardiac complications. Firstly, serum calcium, magnesium and potassium disorders are found frequently in cirrhotic patients and/or patients with portal hypertension, and they are more frequent in patients receiving diuretics. Secondly, obesity is associated with two liver diseases usually found in transplanted patients: hepatic steatosis and hepatocarcinoma,<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">46</span></a> obesity being a risk factor for coronary vascular disease. Some of the diseases leading to liver transplant may be associated with heart disease, as is the case with haemochromatosis. Thirdly, and as was described in this paper, internal milieu abnormalities produced during bleeding and transfusion create a risk of citrate intoxication,<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">47</span></a> with ventricular contractile failure<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22,48</span></a> and cardiac arrhythmias.</p><p id="par0100" class="elsevierStylePara elsevierViewall">The presence of acute haemorrhage during liver transplantation is frequent and usually requires massive blood transfusions resulting in a risk of ion abnormalities. In turn, this results in a predisposition to cardiac failure, rhythm abnormalities, and even death. Preventive strategies are recommended in order to avoid those complications. They include:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">•</span><p id="par0105" class="elsevierStylePara elsevierViewall">Selection of blood product volumes with shorter storage time, and red blood cell washing.<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,49</span></a></p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">•</span><p id="par0110" class="elsevierStylePara elsevierViewall">Systematic calcium administration if blood products are required during transplant surgery. It may be used in infusion at a dose of 5<span class="elsevierStyleHsp" style=""></span>mg/kg/h for calcium chloride, or 15<span class="elsevierStyleHsp" style=""></span>mg/kg/h for calcium gluconate, as long as there is significant bleeding requiring transfusion.</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">•</span><p id="par0115" class="elsevierStylePara elsevierViewall">Aggressive treatment for hypocalcaemia during transplant surgery: boluses of 5–10<span class="elsevierStyleHsp" style=""></span>mg/kg of calcium chloride or 15–30<span class="elsevierStyleHsp" style=""></span>mg/kg of calcium gluconate.</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">•</span><p id="par0120" class="elsevierStylePara elsevierViewall">Immediate correction of factors favouring citrate intoxication, namely, acidosis and hypotension.<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22,50</span></a></p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">•</span><p id="par0125" class="elsevierStylePara elsevierViewall">Correction of hyperkalaemia (with diuretics, glucose insulin solutions, bicarbonate or beta-agonists), hypercalcaemia and hypomagnesaemia, which may be present in transplant patients already in the immediate preoperative period.</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">•</span><p id="par0130" class="elsevierStylePara elsevierViewall">Use of loop diuretics to avoid excess increase of preload when there is a need to administer large plasma volumes for the treatment of coagulopathy.</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">•</span><p id="par0135" class="elsevierStylePara elsevierViewall">Evaluate, together with the surgeons, the need for washing the graft with at least 500<span class="elsevierStyleHsp" style=""></span>ml of fluid before reperfusion, in order to avoid rises in serum potassium that may lead to cardiac arrest.<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a></p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">•</span><p id="par0140" class="elsevierStylePara elsevierViewall">Avoid reduced oxygen supply and increased oxygen consumption by the myocardium (hypotension, anaemia, tachycardia, and hypertension) in order to minimize ischaemia as an additional etiologic factor of arrhythmias, and heart failure.</p></li></ul></p><p id="par0145" class="elsevierStylePara elsevierViewall">Calcium and potassium abnormalities in patients with massive intraoperative haemorrhage during liver transplant surgery must be addressed actively and aggressively with a multidisciplinary approach.</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Funding</span><p id="par0150" class="elsevierStylePara elsevierViewall">None.</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Conflicts of interest</span><p id="par0155" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:2 [ "identificador" => "xres354023" "titulo" => "Abstract" ] 1 => array:2 [ "identificador" => "xpalclavsec335362" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres354024" "titulo" => "Resumen" ] 3 => array:2 [ "identificador" => "xpalclavsec335363" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Methodology" ] 6 => array:3 [ "identificador" => "sec0015" "titulo" => "Massive haemorrhage" "secciones" => array:2 [ 0 => array:3 [ "identificador" => "sec0020" "titulo" => "Hypocalcaemia" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0025" "titulo" => "Citrate intoxication" ] 1 => array:2 [ "identificador" => "sec0030" "titulo" => "Treatment of hypocalcaemia: calcium gluconate and calcium chloride" ] ] ] 1 => array:3 [ "identificador" => "sec0035" "titulo" => "Hyperkalaemia" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0040" "titulo" => "Hyperkalaemia and acidosis" ] 1 => array:2 [ "identificador" => "sec0045" "titulo" => "Hyperkalaemia and blood transfusion" ] 2 => array:2 [ "identificador" => "sec0050" "titulo" => "Hyperkalaemia in liver transplant" ] 3 => array:2 [ "identificador" => "sec0055" "titulo" => "Clinical manifestations" ] ] ] ] ] 7 => array:2 [ "identificador" => "sec0060" "titulo" => "Conclusions" ] 8 => array:2 [ "identificador" => "sec0065" "titulo" => "Funding" ] 9 => array:2 [ "identificador" => "sec0070" "titulo" => "Conflicts of interest" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2013-02-26" "fechaAceptado" => "2014-03-24" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec335362" "palabras" => array:5 [ 0 => "Hypocalcaemia" 1 => "Citrate intoxication" 2 => "Hyperkalaemia" 3 => "Massive bleeding" 4 => "Liver transplantation" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec335363" "palabras" => array:5 [ 0 => "Hipocalcemia" 1 => "Intoxicación por citrato" 2 => "Hiperpotasemia" 3 => "Hemorragia masiva" 4 => "Trasplante hepático" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Rapid transfusion of blood products and the presence of ionic changes as hypocalcaemia and hyperkalaemia are common in liver transplantation. The objective of this paper is to give the reader a clear and practical description of the etiological factors, biochemical mechanisms, diagnosis and treatment of the calcium and potassium plasmatic disorders associated with massive transfusion. The peculiarities that arise in the clinical setting of liver transplant surgery and citrate intoxication are highlighted. A non-systematic review of literature was conducted in MEDLINE, OVID and Cochrane databases. Correct and early anaesthetic management of calcium and potassium disorders prevents serious complications in intraoperative bleeding risk surgeries such as liver transplantation.</p>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La transfusión rápida de hematocomponentes y la presencia de alteraciones iónicas como la hipocalcemia y la hiperpotasemia son frecuentes en el trasplante hepático. El objetivo de este trabajo es brindar al lector una descripción ordenada y práctica de los factores etiológicos, mecanismos bioquímicos, diagnóstico y tratamiento de las alteraciones del calcio y del potasio asociadas a la transfusión masiva. Se destacan las particularidades del contexto clínico de la cirugía de trasplante hepático y se describe la intoxicación por citrato y sus factores predisponentes. Se realizó una revisión no sistemática de la literatura en las bases de datos MEDLINE, OVID y Cochrane. El manejo anestésico correcto y precoz de las alteraciones del calcio y del potasio evita complicaciones graves en el intraoperatorio de las cirugías con riesgo de hemorragia, como el trasplante de hígado.</p>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Rando K, Vázquez M, Cerviño G, Zunini G. Hipocalcemia, hiperpotasemia y hemorragia masiva en el trasplante de hígado. Rev Colomb Anestesiol. 2014;42:214–219.</p>" ] ] "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "fuente" => "<span class="elsevierStyleItalic">Source</span>: Authors." "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=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Solution \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Elemental calcium \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Total calcium (10<span class="elsevierStyleHsp" style=""></span>ml formulations) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Osmolarity \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10% calcium chloride \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">27<span class="elsevierStyleHsp" style=""></span>mg (1.36<span class="elsevierStyleHsp" style=""></span>mEq/l) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">270<span class="elsevierStyleHsp" style=""></span>mg/10<span class="elsevierStyleHsp" style=""></span>ml \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2000<span class="elsevierStyleHsp" style=""></span>mOsm/l \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10% calcium gluconate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9<span class="elsevierStyleHsp" style=""></span>mg (0.46<span class="elsevierStyleHsp" style=""></span>mEq/l) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10<span class="elsevierStyleHsp" style=""></span>mg/10<span class="elsevierStyleHsp" style=""></span>ml \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">680<span class="elsevierStyleHsp" style=""></span>mOsm/l \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab528965.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Differences in the composition of calcium chloride and calcium gluconate.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:50 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Intraoperative cardiac arrests in adults undergoing noncardiac surgery: incidence, risk factors, and survival outcome" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "S. 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| 2023 September | 6 | 12 | 18 |
| 2023 August | 13 | 2 | 15 |
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| 2022 October | 20 | 9 | 29 |
| 2022 September | 7 | 4 | 11 |
| 2022 August | 8 | 6 | 14 |
| 2022 July | 4 | 5 | 9 |
| 2022 June | 13 | 5 | 18 |
| 2022 May | 30 | 6 | 36 |
| 2022 April | 9 | 11 | 20 |
| 2022 March | 8 | 4 | 12 |
| 2022 February | 6 | 3 | 9 |
| 2022 January | 2 | 5 | 7 |
| 2021 December | 11 | 11 | 22 |
| 2021 November | 8 | 5 | 13 |
| 2021 October | 6 | 6 | 12 |
| 2021 September | 7 | 8 | 15 |
| 2021 August | 8 | 6 | 14 |
| 2021 July | 4 | 4 | 8 |
| 2021 June | 3 | 10 | 13 |
| 2021 May | 11 | 4 | 15 |
| 2021 April | 8 | 6 | 14 |
| 2021 March | 10 | 9 | 19 |
| 2021 February | 2 | 6 | 8 |
| 2021 January | 5 | 7 | 12 |
| 2020 December | 3 | 7 | 10 |
| 2020 November | 2 | 3 | 5 |
| 2020 October | 1 | 2 | 3 |
| 2020 September | 5 | 7 | 12 |
| 2020 August | 7 | 7 | 14 |
| 2020 July | 5 | 7 | 12 |
| 2020 June | 4 | 3 | 7 |
| 2020 May | 3 | 2 | 5 |
| 2020 April | 6 | 3 | 9 |
| 2020 March | 2 | 6 | 8 |
| 2020 February | 4 | 5 | 9 |
| 2020 January | 7 | 5 | 12 |
| 2019 December | 7 | 4 | 11 |
| 2019 November | 1 | 3 | 4 |
| 2019 October | 2 | 3 | 5 |
| 2019 September | 1 | 2 | 3 |
| 2019 August | 4 | 2 | 6 |
| 2019 July | 2 | 4 | 6 |
| 2019 June | 0 | 4 | 4 |
| 2019 May | 1 | 9 | 10 |
| 2018 December | 1 | 0 | 1 |
| 2018 September | 1 | 0 | 1 |
| 2018 June | 2 | 0 | 2 |
| 2018 May | 25 | 7 | 32 |
| 2018 April | 44 | 8 | 52 |
| 2018 March | 39 | 8 | 47 |
| 2018 February | 19 | 13 | 32 |
| 2018 January | 44 | 15 | 59 |
| 2017 December | 28 | 8 | 36 |
| 2017 November | 38 | 10 | 48 |
| 2017 October | 29 | 18 | 47 |
| 2017 September | 35 | 9 | 44 |
| 2017 August | 53 | 12 | 65 |
| 2017 July | 72 | 15 | 87 |
| 2017 June | 73 | 10 | 83 |
| 2017 May | 67 | 9 | 76 |
| 2017 April | 71 | 12 | 83 |
| 2017 March | 64 | 10 | 74 |
| 2017 February | 36 | 6 | 42 |
| 2017 January | 14 | 11 | 25 |
| 2016 December | 58 | 9 | 67 |
| 2016 November | 40 | 10 | 50 |
| 2016 October | 54 | 9 | 63 |
| 2016 September | 66 | 10 | 76 |
| 2016 August | 45 | 8 | 53 |
| 2016 July | 20 | 10 | 30 |
| 2016 June | 0 | 9 | 9 |
| 2016 May | 2 | 20 | 22 |
| 2016 April | 1 | 24 | 25 |
| 2016 March | 3 | 25 | 28 |
| 2016 February | 2 | 22 | 24 |
| 2016 January | 3 | 22 | 25 |
| 2015 December | 19 | 16 | 35 |
| 2015 November | 54 | 14 | 68 |
| 2015 October | 58 | 9 | 67 |
| 2015 September | 65 | 8 | 73 |
| 2015 August | 46 | 8 | 54 |
| 2015 July | 59 | 7 | 66 |
| 2015 June | 50 | 2 | 52 |
| 2015 May | 48 | 8 | 56 |
| 2015 April | 50 | 13 | 63 |
| 2015 March | 34 | 15 | 49 |
| 2015 February | 33 | 15 | 48 |
| 2015 January | 47 | 6 | 53 |
| 2014 December | 47 | 18 | 65 |
| 2014 November | 30 | 10 | 40 |
| 2014 October | 58 | 14 | 72 |
| 2014 September | 43 | 14 | 57 |
| 2014 August | 39 | 10 | 49 |
| 2014 July | 97 | 16 | 113 |
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