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World Journal for Pediatric and

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DOI: 10.1177/2150135112467213 2013 4: 197World Journal for Pediatric and Congenital Heart Surgery

David P. Martin, Daniel Gomez, Joseph D. Tobias, William Schechter, Carlos Cusi and Robert MichlerSevere Hyperkalemia During Cardiopulmonary Bypass : Etiology and Effective Therapy

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Case Report

Severe Hyperkalemia DuringCardiopulmonary Bypass: Etiologyand Effective Therapy

David P. Martin, MD1, Daniel Gomez, CCP, FPP2,Joseph D. Tobias, MD1, William Schechter, MD3, Carlos Cusi,Cert AT4 and Robert Michler, MD5

AbstractHyperkalemia is considered a medical emergency as it can result in severe disturbances in cardiac rhythm and death. Althoughmany causes of hyperkalemia exist, exogenous red blood cell transfusions are being recognized as the primary perioperativeetiology. The authors report a case of severe intraoperative hyperkalemia associated with the use of allogeneic blood products(packed red blood cells), during a surgical mission to a developing country. The patient was undergoing repeat mitral valvereplacement with cardiopulmonary bypass (CPB) and developed significant hyperkalemia with a serum potassium value of9.9 mEq/L. Successful intraoperative therapies were instituted with a gradual reduction in the serum potassium value to 4.8 mEq,which allowed the patient to be weaned from CPB. The authors review the etiology of hyperkalemia in children including itsrelationship with allogeneic red blood cell transfusions and treatment modalities including specific therapies which can beinstituted during CPB.

Keywordselectrophysiology, cardiopulmonary bypass (CPB), CPB, cell saver, mitral valve replacement

Submitted July 31, 2012; accepted October 16, 2012.

Introduction

Given its significant effects on cardiac rhythm, hyperkalemia

is considered a medical emergency. Although predominantly

an intracellular cation, it is the extracellular concentration of

potassium that affects cardiac rhythm, resulting in morbidity.

In general, hyperkalemia is defined as a serum concentration

greater than 5.5 mEq/L, although various other factors alter

the exact level at which rhythm disturbances and deleterious

adverse effects are seen. The etiologies of hyperkalemia can

generally be divided into factitious (sample hemolysis),

increased intake or administration, factors that cause a

movement from the intracellular to the extracellular

compartment, and decreased renal1 excretion (Table 1).

Additionally, hyperkalemia should be separated into either

acute or chronic in nature, as the acute forms are more likely

to result in cardiovascular consequences. In the perioperative

population, recent attention has focused on the potential for

the rapid administration of allogeneic blood products and

its potential to cause hyperkalemia.2-6 Data from the

perioperative cardiac arrest (POCA) registry in infants and

children clearly demonstrate that following massive blood

loss, hyperkalemia from blood transfusion is the second most

common cause of perioperative cardiac arrest in infants

and children.2

The authors report an 11-year-old girl with rheumatic

heart disease who developed severe transfusion-related

hyperkalemia during cardiac surgery. She was cared for by a

multidisciplinary team during a cardiac surgical humanitarian

mission trip to Lima, Peru under the auspices of Heart Care

International (Greenwich, Connecticut). The etiology of hyper-

kalemia in children is discussed, potential treatment modalities

including novel therapies that can be instituted during

1Department of Anesthesiology & Pain Medicine, Nationwide Childrens

Hospital, Ohio State University, Columbus, OH, USA2Cardiovascular Perfusion Services and Heart Center, Nationwide Childrens

Hospital, Ohio State University, Columbus, OH, USA3Departments of Anesthesiology and Pediatrics, Morgan Stanley Childrens

Hospital of New York-Presbyterian and Columbia University College of

Physicians and Surgeons, New York, NY, USA4 Pediatric Anesthesia Support Services, Morgan Stanley Childrens Hospital of

New York-Presbyterian, New York, NY, USA5Department of Cardiothoracic Surgery, Montefiore Hospital, New York, NY,

USA

Corresponding Author:

David P. Martin, Department of Anesthesiology & Pain Medicine, Nationwide

Childrens Hospital, 700 Childrens Drive, Columbus, OH 43205, USA.

Email: david.martin@nationwidechildrens.org

World Journal for Pediatric andCongenital Heart Surgery4(2) 197-200 The Author(s) 2012Reprints and permission:sagepub.com/journalsPermissions.navDOI: 10.1177/2150135112467213pch.sagepub.com

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Abbreviations and Acronyms

BUN blood urea nitrogenCPB cardiopulmonary bypassECG electrocardiographyPOCA perioperative cardiac arrestZBUF zero-balanced ultrafiltration

cardiopulmonary bypass (CPB) are presented, and its relation-

ship with exogenous red cell transfusions revisited.

Case Report

Institutional review board approval is not required for single

case reports at Nationwide Childrens Hospital (Columbus,

Ohio). Presentation of this case and review of the hospital

course was approved by Heart Care International. The patient

was an 11-year-old, 49 kg girl without major noncardiac

medical problems, who presented for repeat sternotomy and

mitral valve replacement. She presented with severe mitral

regurgitation due to rheumatic heart disease despite mitral

valve repair two years prior. Preoperative echocardiogram

revealed severe mitral regurgitation with left ventricular

dilatation and hypertrophy. Her ejection fraction was preserved

with no regional wall motion abnormalities. Her previous

perioperative mitral value repair course was reported as

uneventful and without major complications. Preoperative

electrocardiography (ECG) revealed no evidence of T wave

or ST segment changes with a normal corrected QT interval.

The patients preoperative serum values of potassium, blood

urea nitrogen (BUN), and creatinine were all normal. Based

on her preoperative hemoglobin and an evaluation of her

peripheral blood smear, there was no evidence of preoperative

hemolysis. On the day of surgery, she was held nil per os for six

hours and transported to the operating room where standard

American Society of Anesthesiologists monitors were placed.

Anesthetic induction included etomidate (0.3 mg/kg), lidocaine

(1 mg/kg), and fentanyl (3 mg/kg). Neuromuscular blockadewas achieved with vecuronium (0.2 mg/kg). Following

anesthetic induction and tracheal intubation, a second

peripheral intravenous cannula, an arterial cannula, and a

central venous cannula were placed. Maintenance anesthesia

included fentanyl (total dose of 15 mg/kg) and isoflurane(exhaled concentration 1%-2%). Following sternotomy andplacement of arterial and venous cannulas, CPB was initiated

without difficulty. The CPB circuit was primed with 700 mL

of Normosol R (Hospira, Inc, Lake Forest, Illinois), 2 units/mL

of heparin, 24 mEq/L of sodium bicarbonate, 50 mL of 25%albumin, and 12.5 g of mannitol. The patient was cooled to

28C. Cardioplegia was administered for cardiac arrest withan initial dose of 15 mL/kg of a 1:1 blood\cardioplegia mixture.

The cardioplegia solution contained 20 mEq/L of potassium.

The patient was re-dosed twice with cardioplegia using a

volume of 7 mL/kg at 30- to 45-minute intervals. Arterial blood

gases were analyzed at regular intervals during the course of

CPB. Potassium levels increased only slightly after the

cardioplegia doses (4.1 mEq/L at baseline to 4.9 mEq/L).

During CPB, the hemoglobin level slowly decreased to

7.2 g/dL and a decision was made to administer 1 unit of

cross-matched, 9-day-old allogeneic packed red blood cells

into the CPB circuit. The blood was administered into the CPB

circuit by gravity flow over 4 to 5 minutes. Serial blood

samples demonstrated only a moderate increase in her

hemoglobin to 9.5 g/dL, while her serum potassium

concentration increased rapidly to 9.9 mEq/L. Testing of the

remaining small amount of the untransfused blood remaining

in the bag demonstrated a potassium concentration of greater

than 20 mEq/L (greater than the upper limit of the point of care

testing device that was used). After successful placement of the

prosthetic mitral value, the patient was rewarmed to 37C onCPB. Although from a surgical standpoint the patient was

ready to be weaned from CPB, the patients serum potassium

had remained at 9.9 mEq/L and her ECG demonstrated peaked

T waves and a wide complex QRS. Zero-balanced

ultrafiltration (ZBUF) was initiated by the perfusion team using

3 L of normal saline. Furosemide 2 mg/kg was administered

intravenously and acidosis was treated with sodium

bicarbonate to achieve a pH 7.45. After an additional60 minutes on CPB with institution of the above mentioned

maneuvers, the patients serum potassium was less than

4.9 mEq/L, with a pH of 7.41 and PaCO2 of 39 mm Hg. She

was weaned from CPB. Milrinone at a dose of 0.5 mg/kg permin and epinephrine at 0.05 mg/kg per min were administeredduring separation from CBP. At the completion of the surgical

procedure, residual neuromuscular blockade was reversed and

the patients trachea was extubated. She was transferred to the

cardiac intensive care unit. Her initial serum potassium value

was 4.8 mEq/L with normal renal function. Over the ensuring

24 hours, the milrinone and epinephrine were weaned off. The

Table 1. Etiologies of Hyperkalemia on Cardiopulmonary Bypass.

Improper electrolyte mixture in the prime solutionFrequently administered or improperly mixed cardioplegiaInappropriate exogenous administration to correct hypokalemic

stateHemolysis

Immune: transfusion reaction, improper type and cross-matchInadequate patientunit identification cross-checkMechanical: long bypass time, excessive suction, excessive pumphead occlusion pressureInadequately occlusive aortic clamp with consequent leakage ofcardioplegia solution into the circulationPretransfusion warming of blood at excessive temperature(>42C)Transfusion of blood that is G6PD deficient orhemoglobinopathicImproperly mixed with a hypo- or hyperosmotic solutionStored or transported at improper temperature

Hypercarbia (inadequate gas sweep, hypermetabolic state)Temperature-related potassium shiftsMetabolic acidosisRenal insufficiency/failure

198 World Journal for Pediatric and Congenital Heart Surgery 4(2)

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remainder of her postoperative course was uncomplicated.

Postoperative echocardiogram showed normal ventricular

function and mitral function.

Discussion

The potassium concentration in collected and stored packed red

blood cells increases dramatically after removal and storage,

with levels reaching 15 to 20 mEq/L following two to three

weeks with the potential for levels greater than 60 mEq/L within

35 days of storage.7,8 It should not be surprising, therefore, that

when packed red blood cells that are not fresh are rapidly

administered, hyperkalemia can occur resulting in cardiac arrest.

Various other factors may further magnify the risk of such occur-

rences including irradiation of the blood product, the age of the

blood since being collected, the volume of the transfusion rela-

tive to the patients circulating blood volume, the volume status

of the patient, the rate of infusion, or the gauge of the intravenous

catheter. The use of smaller catheters may create greater shear

forces at high infusion rates leading to hemolysis. Additionally,

the presence of a low cardiac output state may limit the ability to

redistribute the extracellular potassium.

Therapy for hyperkalemia includes cardiac membrane

stabilization with calcium and aggressive treatment of cardiac

dysrhythmias, cessation of the administration of all sources of

exogenous potassium, and lowering the plasma concentration

of potassium via excretion and intracellular shifts.1 Methods

of enhancing the shift of potassium from the extracellular to the

intracellular space include the administration of insulin with

glucose, b-adrenergic agonists, and creating an alkalotic milieuthrough the administration of sodium bicarbonate or increasing

minute ventilation. Additional therapies aimed at enhancing

the excretion of potassium include the administration of loop

diuretics, use of cation exchange resins, such as sodium

polystyrene sulfonate (Kayexalate, sanofi-aventis, Laval,

Quebec), or dialysis techniques including ultrafiltration. The

latter was used during CPB in our patient to lower the serum

potassium concentration.

Treatment options to treat or prevent hyperkalemia during

CPB include washing of packed red blood cells with an

autotransfusion device prior to administration, dilution of the

transfusate with equal volumes of normal saline, or ZBUF with

a balanced electrolyte solution plus sodium bicarbonate and

calcium supplementation. Auto-transfusion device (cell saver)

washing has been shown to be superior to blood bank washing

as the acid metabolites are truly washed off rather than

hemodiluted.9 For this process, many centers use physiologic

(0.9%) sodium chloride; however, our institution has adoptedNormosol R, after a quality assurance investigation showed

increased sodium concentration in patients receiving cell

salvage blood. Swindell et al reported that using normal saline

as the wash solution resulted in an increase in the serum sodium

concentration from a prewashed value of 126 + 7.0 to147.6+ 1.4 mEq/L.9

Zero-balanced ultrafiltration was the technique used in our

patient during CPB. It involves a technique where the volume

administered into the CPB pump equals the volume that is

removed via ultrafiltration. This technique may be used

pre-CPB when blood priming of the circuit is necessary and

an autotransfusion device is unavailable as well as during CPB.

The sieving coefficient of the filter is high for electrolytes that

are not protein bound; therefore, bicarbonate and calcium

supplementation is required as these cations are lost in addition

to potassium. Our institutional technique is to add 24 mEq/L of

sodium bicarbonate and 200 mg/L of calcium chloride to

Normosol R to achieve a physiologic concentration.

Over the past few years, there has been an increased

recognition and perhaps incidence of hyperkalemia related to

the administration of allogeneic blood products. Of the

reported cases in the literature involving children, the majority

have been in children less than 6 to 12 months of age.

Irradiation of blood makes the cells more prone to hemolysis

and should be utilized immediately. Prevention remains the key

factor in avoiding such complications including the use of

blood that is less than seven days old, when caring for children

less than one year of age or when large volumes of blood are

administered. If this is not feasible, consideration should be

given to washing the blood product prior to administration. If

this cannot be accomplished in the blood bank, a standard cell

saver can be used as noted above. If feasible, the blood shouldbe

administered slowly through at a 22-gauge or greater peripheral

intravenous cannula. The rate of transfusion is recommended to

be slow in order to allow for redistribution and equilibration of

potassium. Additionally, the presence of a low cardiac output

state, such as during acute hypovolemia, can predispose to

hyperkalemia as redistribution of extracellular potassium is

impaired. If time allows, one should consider point-of-care

sampling of the blood for determination of potassium level prior

to transfusion. If the blood cannot be washed and life-threatening

anemia with hypovolemia is present, consideration should be

given to diluting the older blood with normal saline; however, a

larger volume of transfusate will be needed to achieve the desired

hemoglobin concentration.Once intravascularvolumeandhemo-

globin are restored, the judicious use of loop diuretics may be

needed. Fortunately, in our case, our patient was still on CPB and

the hyperkalemia was easily treated using ZBUF with a prompt

return of the serum potassium concentration to a normal value,

thereby allowing weaning from CPB. The use of techniques that

can minimize patient exposure to homologous blood is also an

important step in avoiding the risks of transfusion therapy. These

include autologous donation including phlebotomy in the operat-

ing room prior to surgical incision, intraoperative cell salvage,

and the use of antifibrinolytic agents.10

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to

the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research,

authorship, and/or publication of this article.

Martin et al 199

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