Fluid and Electrolyte Therapy

Parental FluidsInfusion:Administration of > 100 ml fluid by parentral routeTonicityOsmotic pressure of fluid in relation to plasmaParentral fluids can beIsotonic: osmotic pressure of the fluid = OP of the plasma = 290 mOsmol/LHypertonic: OP > OP of plasma by > 50.Hypotonic: OP < OP of plasma at least by 50

Parental FluidsThe tonicity of fluid has direct effect on fluid and electrolyte when infused into circulation Hypertonic OP of plasma movement of water from cell to plasma cell dehydration esp. in brainHypotonic solution OP of plasma causing fluid to invade cells.Isotonic fluid excess ECF blood volume circulatory overload.

Parental FluidsWhats the importance of knowing the osmolarity of infusion fluidAlert to fluid and electrolyte imbalances that may occurHyperosmolar fluid should be infused in large vein with large blood volume to dilute fluid.Tonicity of fluid affects the rate at which it can be infused

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*Cell in a hypertonic solution

*Cell in a hypotonic solution

How to Calculate OsmolarityOsmolarity=Conc.in mg/L/(atomic wt x valence)Calculate osmolarity of NS 0.9 % NaclAtomic wt 58.5 mg1 L of 0.9 % contain 9000 mg NaCl1 atomic wt 58.5 2 mOsmols 9000mg XX= 307.7 mOsmol isotonic

How to Calculate OsmolarityCalculation of Osmolarity of DextroseMWt = 198 mgD5W 1 L contain 50 g198 mg 1 mOsmol50000 mg XX = 252.5 mOsmol isotonic

Fluid and electrolyte therapy

Physiology of body water balance

Physiology of Body Water BalanceBody water is divided to 3 compartmentsIntracellular: ICF, 40-50% of body wtInterstitial: 11-15%Vascular: 5%Extra-cellular fluid ECF: interstitial +vascularActual amount of body water differs according toAgeSexBody composition

Body Fluid Compartments:ICF:55%~75%IntravascularplasmaX 50~70% lean body weightExtravascularInterstitial fluidTBWECF3/41/4Male (60%) > female (50%)Most concentrated in skeletal muscleTBW=0.6xBWICF=0.4xBWECF=0.2xBW2/31/3

Physiology of Body Water BalanceNewborn 70% 0f WT water1-year-old 60% of WT waterMen: higher water content due to greater muscle massObese: less water because fat cells have minimal ICFUse ideal body weight when estimating TBW for obeseElderly: less water due to less muscle mass

Physiology of Body Water BalanceWater moves between the 3 compartments at the level of the capillariesThe vol in each compartment remains constant under normal conditionsRegulated by hydrostatic and oncotic pressureHydrostatic; determined by cardiac output and arterial tone which determine BP = 17 mmHg and pushes water to interstitial spaceoncotic pressure: proteins in the vascular space pull water

Fluid compartmentsICF

Fluid compartmentsICFECFInterstitial Plasma

Fluid compartmentsICFECFInterstitial Plasma

Fluid compartmentsICFECFInterstitial PlasmaCapillary Membrane

Fluid compartmentsICFECFInterstitial PlasmaCapillary MembraneCell Membrane

Colloid osmotic pressureECFInterstitial PlasmaCapillary MembraneCapillary membrane freely permeable to water and electrolytes but not to large molecules such as proteins (albumin).

Colloid osmotic pressureECFInterstitial PlasmaCapillary MembraneCapillary membrane freely permeable to water and electrolytes but not to large molecules such as proteins (albumin).

Colloid osmotic pressureECFInterstitial PlasmaCapillary MembraneCapillary membrane freely permeable to water and electrolytes but not to large molecules such as proteins (albumin). The albumin on the plasma side gives rise to a colloid osmotic pressure gradient favouring movement of water into the plasma

H2OH2O

Colloid osmotic pressureECFInterstitial PlasmaCapillary MembraneCapillary membrane freely permeable to water and electrolytes but not to large molecules such as proteins (albumin). The albumin on the plasma side gives rise to a colloid osmotic pressure gradient favouring movement of water into the plasmaThis is balanced out by the hydrostatic pressure differenceH2OH2O120/80H2OH2O

Physiology of Body Solute BalanceOsmotic pressure keeps the vol of three compartments constantThe concentration of electrolyte in each compartment creates osmotic pressure that holds the water in each space

Body Water DisturbancesEvaluated as total volume and individual compartmentsDehydration:Fluid volume is low in all three compartmentsHypovolemia:Low vascular fluidTotal body water overloadTBW > 60%Not specify abnormalities in individual compartmentsDistribution of water must be known before appropriate action can be takenEdemaCollection of fluid in interstitial space due to low oncotic pressure in the vascular compartment. E.g low albumin levels

Distribution of Ions in Each CompartmentTable 9.1OsmolarityNormal 280-300 mOsmol/LECF: Na and ClICF: K and Po4Concentration of other ions is too low to contribute to osmotic gradientOther osmotically active substances: glucose , urea, and lipids.Osmolarity is determined by all the aboveNon-Electrolyte contribution is little

Composition of Body Fluids: Osmolarity = solute/(solute+solvent) Osmolality = solute/solvent (290~310mOsm/L) Tonicity = effective osmolality Plasma osmolility = 2 x (Na) + (Glucose/18) + (Urea/2.8) Plasma tonicity = 2 x (Na) + (Glucose/18)

OsmolarityEffective Osmolarity:Twice the Na concentration in the ECFCalculation of osmolarity(mmol/Kg)2 X Na ( mEq/L) + glucose ( mg/L)/18 + urea ( mg/L)/2.5

The Kidney and Osmolaritythe kidney attempt to maintain osmolarity by increasing excretion of glucose and urea when their concentrations riseif not possible or sufficient it will increase excretion of Namaninating normal osmolarity is more important than maintaining solute compositionwhen concentration of solutes in any compartment changes water moves to reestablish osmotic pressure

Maintenance of Fluid and Electrolyte RequirementsMaintained by equilibrium between oral intake and evaporation from skin and lungs and renal excretion.Loss through the evaporation depends on body surface area and respiratory rate and remains constantThe kidney or output by the action of ADH and aldosterone

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Maintenance of Fluid and ElectrolyteADH: Regulates water reabsorbed in the distal tubules according to osmolarity of ECF osmolarity ADH water reabsorption osmolarity water reabsorption vascular tone and lead vasoconstriction esp. of those leading to the kidneyAldosterone Na reabsorptionsecretion stimulated by low blood volume and low total NaADH, aldosterone, and thirst center work to maintain total body vol and Na within 1% of normal over wide variations in daily intake.

Regulation of Fluids: Renal sympathetic nerves Renin-angiotensin- aldosterone system Atrial natriuretic peptide (ANP)

Fluid RequirementThe amount of water and electrolyte that is needed to replace insensible loss,, maintain adequate perfusion and result in urine output sufficient to excrete metabolic waste varies nonlinearly with changes in body sizeThe first 10 Kg 100ml/kgThe second 10 kg 50ml/kgAnd each Kg beyond 20 kg requires 20 ml/kgSame formula used for childrenUse IBW for obese patientsIn fever, add extra 10% of calculated water for every 1 C elevation.

FLUID REQUIREMENTS

SourcesLossesWater1500 mlUrine1500 mlFood800 mlStool200 mlOxidation300 mlSkin500 mlResp. Tract400 mlTotal2600 mlTotal2600 ml

Electrolyte RequirementsVaries because the kidney constantly adjusts secretion or Na excretion to maintain normal vascular volume and compositionReduce Na excretion to zero by increasing K and H excretionAmount of electrolyte needed to maintain normal homeostasis without stimulating the secretion of ADH and aldosterone is linearly related to water requirementsTable 9.2Cations must be given with an equal number of anions to maintain electrical neutrality

How to determine daily fluid and electrolyte requirementsDetermine basal need or maintenance requirementsCorrect for existing disease or imbalanceAdjust according to clinical condition

MAINTENANCE vs. REPLACEMENTMaintenance:Provide normal daily requirements:Water: 2.5 L Sodium or NSKCl 40-60 meq/LExample:D5 NS with KCL 20 meq/L running at 100 ml/hr

Denis Wormington

MAINTENANCE vs. REPLACEMENTReplacement:Replace abnormal losses with a fluid and electrolytes similar to that which was lost.

How to Evaluate Water and Electrolyte BalanceClinical findings:Central venous pressure: Give accurate measure of changes in blood volumePulse:

High pulse and not easily obliterated

Circulatory overload AAND CO due to excess fluid

Bonding, not easily obliterated

Drop in BP, impending circulatory collapse

Regular pulse, easily obliterated

Low CO due to low Blood Vol.

Peripheral Veins:Normal filling and emptying time 3-5 sec

Slow filling > 3-5 sec

Fluid depletion or Na depletion or EC dehydration

Slow emptying > 3-5 sec

Over hydration and excess blood volume

Veins engorged

plasma vol

Weight:Body weight at the same time each day using the same scale

Loss of 1Kg

Loss of 1 L fluid

Loss of 5% of weight

Moderate dehydration

Loss of 9-10%

Sever dehydration

e-ThirstIn old age decrease thirst sensationf- Fluid intake and outputOutput :urine , stool, vomitusinsensible loss: skin and lungs 1L/d under constant conditions. Related to body surface area and respiratory rateurine output ideal 30-50 ml/hrurine output > 200 ml/hr to much fluids infused at rapid rate

Diagnosis of Fluid and Electrolyte DisordersChanges in body fluids:Volume overload edema, heart failure, weightVolume depletion: signs of dehydrationChanges in electrolytesMay be asymptomatic or symptomatic depending on type and degree of abnormalityDiagnosis by serum levelsAvoid rapid correction

Disorders of Body Water and SoluteSodiumThe osmotically active substance in the greatest concentration in the vascular and the interstitial compartmentNormal conc. 135-145 mmol/LHyponatremia and hypernatremia refer only to concentration Do not describe whether there is total , or normal sodium in the body

Closed Head Injury32 year old female, MVC, GCS -7, intubated, with CT scan showing SAH, cerebral edema. ICP monitor shows a pressure of 27. CPP 55.

Over the next several days, Na+ > 150.

What do you think? What do you do?

DIABETES INSIPIDUSSigns[Na+] 150Urine specific gravity 1.007polyuria, clear urine dDAVP 1g sq raises urine osmolality in 2 hoursTreatmentfree water deficit = (0.6) x (Kg) x ([Naserum/140] -1)dDAVP 2g sq every 12 hoursfor every L water deficit [Na+] will rise 3 mEq above 140

Hypernatremia sodium conc. due to free water deficit salt intake cannot cause in total body Na if renal function is adequateSymptomsSee table 3Important Sx do not appear until Na > 160Mainly due to CNS dehydrationTreatmentDepends if the cause is to little water or to much NaShould not be rapid as not cause new CNS problemsEquilibrium across BBB is slower and rapid changes can cause seizures

HypernatremiaHypernatremia from water lossThere is in total body water from all fluid compartments interstitial and intravascualr Na and intracellular K to produce equilibriumWater deficit (L) = { 1-140/ measured serum Na ( mmol/l)} x body weight ( kg) x 0.6Use electrolyte free oral or IV solutionse.g. D5W given over 18-24 hrsIn addition to calculated maintenance fluid and electrolyte

HypernatremiaHypernatremia from increase amount of Na treatmentRemoval of Na byDiuretics and D5W to renal elimination while maintaining total body

Found Down45 yo WM, found down, presumed to be assaulted, well known to ED for EtOHCT head - hygromas, small ICHlabs:Na = 118K = 2.4Cl = 74

What do you think? What do you do?

Severe HyponatremiaCorrect sodium to above 120 mEq/dlNaCl + 40 mEq/L KCl3% Salinefurosemide diuresis (euvolemic)serial electrolytesbe prepared to handle seizures Replace potassiumCl should correct itself

HyponatremiaNa < 135Important symptoms do not appear until < 120See table 9.3Sx result from CNS water intoxicationTypes DilutionalDepletionFactitious

Hyponatremia-DilutionalTotal body sodium is but TBW is to a greater degreeCauses : cirrhosisCHFEffective cardiac output to kidney is diminished ADH and aldosterone secretion Na and water retention edema due to increase size of interstitial compartmentTreatmentSalt and water restrictionBest rest to increase venous return to the heartCorrection of the primary disorderNot diuretics :cause Na excretion that exceeds water elimination

ELECTROLYTE DISORDERSHypotonic Hyponatremia

Increased ECVDecreased ECVNormal ECVEdematous statesHypovolemic statesSIADHCHFCirrhosisRenal dzDiuretic inducedGI lossesSydrome of inappropriate antidiuretic hormoneExcess of TB Na and waterDepletion of water and NaExcess of water: dilutionalTreatment:DiureticsWater & Na restrictionCHF- cardiac glycosidesWater and Na replacementFluid restrictionFurosemide and NSChronic: Declomycin

Hyponatremia - DepletionTrue decrease in total body NaWith or without water deficitSigns of dehydration: dry mucos membrane, skin tenting, and lethargyCauses:GI loses: vomiting, diarrheaExcessive diureticsAdrenal insufficiencyReplacement of losses form perspiration with solute free waterSodium deficit = {140-measured serum Na(mmol/L)} x body weight (kg) x 0.6Use 0.9% saline (155 mmol of Na) OR 3% saline (500 mmol Na)In addition to daily maintenance fluid and electrolyte

Hyponatremia - Factitious hyponatremiaAccumulation of osmotically active substances such as glucose and lipids in the vascular spaceNa is diluted as water moves from the interstitial to vascular to normalize the osmotic pressureUsually mild hyponatremiaNa 1.6 mml/L for every 5.3 mmol/l increase in glucoseTreatmentCorrect underlying disorder

Alteration in Fluid Compartment IntegrityCausesTraumaTissue ischemiaEndotoxemiaHypoalbuminemiaDecreased cardiac output

Alteration in Fluid Compartment IntegrityMechanismDamage of the capillary membranescapillary leak syndrome: increase in capillary pore sizewater, solutes, proteins flow into interstitial space(third space)the leak can be localized to area of injury as in surgery to trauma or generalized as in septic shockDistruption of the hydrostatic & oncotic pressurethe amount of fluid lost varies with degree of injurycan cause severe hypovolemia that causes CV collapse and death

Signs of hypo / hypervolaemia:Signs of Volume depletion Volume overloadPostural hypotension hypertensionTachycardia tachycardiaAbsence of JVP @ 45o Raised JVP Decreased skin turgor OedemaDry mucosa Pleural effusionsSupine hypotension Pulmonary oedemaOliguria AscitesOrgan failure Organ failure

I- HypovolemiaSymptomsTachycardiaLow central venous pressureLow pulmonary wedge pressureDecrease urine outputBP is not a good measure because increase sympathetic tone can maintain normal BPTreatmentCorrecting the underlying disorderReplacement of lost intravscualr fluids with solution of same compositionNo Blood because blood elements are not lost

Types of Replacement Fluids1-Crytalloidcontain electrolyteNS and lactate ringer most commonly Isotonic with ECF2-Colloidcontain plasma protein or other colloidal moleculeThree typesa- plasma protein fraction PPF85% albumin & 15% globulin available as 5% solutionb- albuminavailable as 5% and 25% c-hetastarchavailable as 6% solutionhas same homodynamic effect as albuminnot extracted from pooled human plasmaLess expensive than PPF or albumincontain 130-160 mmol of Na & Cl/L

Parenteral Fluid Therapy: Crystalloids: - contain Na as the main osmotically active particle - useful for volume expansion (mainly interstitial space) - for maintenance infusion - correction of electrolyte abnormality

Crystalloids: Isotonic crystalloids - Lactated Ringers, 0.9% NaCl - only 25% remain intravascularly Hypertonic saline solutions - 3% NaCl Hypotonic solutions - D5W, 0.45% NaCl - less than 10% remain intra- vascularly, inadequate for fluid resuscitation

Colloid Solutions: Contain high molecular weight substancesdo not readily migrate across capillary walls Preparations - Albumin: 5%, 25% - Dextran - Gelifundol - Haes-steril 10%

Use of colloid is controversial because:only small amounts of protein move into 3rd spacetemporarily decrease the fluid migration rate into the third spacemay exacerbate hypovolemia after 24-36 hrs when it moves to third space itselfUses of colloidsalbumin levels are low 20-25 g/Laggressive crystalloid therapy is not restoring intravacualr volumeRate fluid administration in hypovolemiamust meet/exceed the rate of loss to maintain tissue perfusionurine output must al least 0.5 cc/kg/hrMonitoring parameters:heart rateCVPUrine output

II- hypoalbuminemiaResult in hypovolemia with edemaMechanismNo capillary leakLow oncotic pressure moves fluid to the interstitial spaceTreatment:Albumin or hetstarch to normalize oncotic pressure and resolve edema

III- hypovolemia due to decreased cardiac outputCauses:CHFCardiomyopathyMICannot be corrected using fluidsHypovolemia on arterial side due pump failureThe venous side is overloadedPatient may have edemaTreatmentDrugs that improve cardiac output ( inotropics)

IV- hypovolemia from blood lossUse whole blood or packed red blood cells with normal saline or lactate ringer to raise HCT to 25% and normal circulating volume

Major electrolytes Na, Cl, K, bicarbonate, ca, Mg, Po4Cl is the major anion in the ECF and has no physiological functionK, Ca, Mg maintain membrane potential for nerve conduction and muscle contractiongenerate the energy needed to maintain these potentialsdo the work of body functions and movement Po4the main reservoir is ICF and boneserum levels fall slowly when intake is lownumerous hormonal and homeostatic mechanism exist to keep serum levels with normal rangeserum levels is low in relation to intracellular concentrationconcentration in the serum controls physiological activities

PotassiumAmount in vascular space = 0.4% of total body KNL = 3.5-5 mmol/L (Serum levels are usually indicative of amount in body)Route of excretion;Elimination by the kidneyCan be increase when intake is highKidney cannot conserve KChanges in acid-base balance alter location of KAcidosis;K exchanges for H as an attempt to hide and buffer protons in ICFAlkalosisThe opposite occursSerum K will rise or fall by 0.6 mmol/L for very 0.1 change in PH from 7.4

Metabolic Alkalosis and HypokalemiaIntracellular Fluid

H+ExtracellularFluidK+

Metabolic Acidosis and HyperkalemiaIntracellular Fluid

K+ExtracellularFluidH+

HDU CodeA Code Blue is called in the HDU.

65 yo male with ESRD has arrested awaiting his dialysis treatment. CPR and resuscitation are in progress and an IV has been established.

Diagnosis?HYPERKALEMIATreatment CaCl2 10% - 1 ampule Sodium Bicarbonate - 1 ampule D50 & Insulin 10 U 2 - agonist nebulizer- cellular K Kayexalate

HyperkalemiaTrue medical emergencyManifests as sudden cardiac arrhythmia K > 6See table TBK can be high , low or normal

Hyperkalemia: CausesDecreased Renal Excretion CRF and ARF Drug induced: K-sparing diuretics (spironolactone, triamterine, amiloride)Angiotensin converting enzyme inhibitorsNSAIDS

Hyperkalemia: CausesRedistribution Trauma, burns Acidosis Hyperosmolar states Increased intake Salt substitutes Blood transfusions K salts of antibiotics

Hyperkalemia TreatmentDiscontinue any exogenous sources such as Iv fluids or drugsCorrect bynormalizing neuromuscular membrane potentialshifting ions back into intracellular spaceremoving K from the bodyshould be initiated as soon as possible because they act slowlythey will not correct cardiac arrhythmia in timely fashionnot acute treatment

Diarrhea Dysrhythmia68 yo female on digoxin for chronic CHF, presents to the SIU for colitis as evidenced by copious diarrhea.

The patient is weak and lethargic and ectopic beats are noted on her ECG.

Hypokalemia

replacement 10 mEq/hr via peripheral IV10 mEq 0.1 mEq/L increase in serum KRemember to check the Mg level too

HypokalemiaCan be a cardiac emergency if < 3Can exhibit ms weakness and malaise before ECG changes appearSee table 9.9

Hypokalemia: CausesDecreased dietary intakeRedistribution Insulin Metabolic Alkalosis Dehydration

Hypokalemia: CausesIncreased Urinary or GI Losses Diuretics NG Suction Diarrhea

Hypokalemia: Causes4.Drugsa. Urinary wasting: aminoglycosides, amphotericin B, corticosteroids, diuretics, levodopa, nifedipine, penicillins, rifampinb. Gastrointestinal losses: laxativesc. Redistribution: Beta-2 agonists, lithium

TreatmentCorrection of underlying disease or discontinuation of drug therapy contributing to hypokalemia.Intracellular deficit almost always accompanied hypokalemiaLarge amount may need to be given before TBK and serum K normalizeOral or IV shift slowly to ICF so rate of administration must be slow to prevent hyperkalemia.

Hypokalemia: Treatment/Estimation of Deficit If serum K > 3meq/L: 100-200 meq required per each change in serum K of 1 meq/LIf serum K < 3 meq/L:200-400 meq required per each change in serum K of 1 meq/L

Hypokalemia: Treatment/Estimation of Deficit

Example: Serum K = 2.5 How much K is required to correct serum K to 4.0?Step 1To increase from 2.5 to 3.0: 200-400 meq X 0.5=100-200meqStep 2To increase from 3.0 to 4.0: 100-200 meq X 1.0=100-200meqTo Total=200-400meq

HypokalemiaIV Replacement:Ideal IV rate 10 mmol/hr KCL >10 can cause pain and phelephitis at the IV sitedose: 30-40 mmol in D5W over 3-4 hrsserum K is checked after 1-2 hrpatients with sever hypokalemia and continued K wasting require large dosesmay need 20-50 mmol/hr using a central line to avoid phlebitis

HypokalemiaOral replacement:KCL cause GI irritation and vomiting when given > 20 mmol/dose or 60 mmol/dayBad tasteLarge deficits cannot be replaced by mouth

Hypokalemiahypokalemia secondary to hyponatremiaalways accompanied by hypochloremic alkalosisrenal conservation of Na causes secretion of K and Hfor every 3 mmol Na reabsorbed 2 mmol K and 1 mmol H are excretedTXCorrection of hypoantremia and alkalosis with hypokalemiaKCL is TOCCl loading will lead to excretion of bicarbonate and resolution of alkalosis

ChlorideMajor anion in ECFHas no physiological functionGoes up and down with TBNaChanges cause acid-base disturbances; because electrical neutrality must be maintained and so serum HCO3 will changeIn acidosis or alkalosis changes in CL should not be corrected by giving or restricting ClUntil the cause of acid-base disorder is correctedCL levels may normalize naturally

HyperchloremiaCL > 105 mmol/LCauses :Metabolic acidosis or respiratory alkalosisHypernatremiaChloride loadingTreatmentCorrect underlying disorder

Cause

Treatment

Metabolic acidosis or respiratory alkalosis

Correct the disturbance

Chloride loading

Adjust Iv fluid

Use acetate salts instead of chloride salts

Change NS to lactate ringer or

NS

Hypernatremia due to over ingestion of NaCl

Free water replacement and diuresis

Hypernatremia due to water loss

Electrolyte free water replacement

Hypochloremia:CL < 95 mmol/LCauses: chloride loss through vomiting or diarrheanasogastric suctiondiuretic therapyhyponatremia : compensatory mechanism to maintain electrical neutrality in ECF

Cause

Treatment

Nasogastric suction or vomiting

Loss of large amounts of Cl and acid

Replacement of the volume lost with high chloride containing solutions e.g. NS or lactated ringer

diuretics

increasing NaCl intake

reducing diuretic dose

hyponatremia and hypokalemia

saline and KCl

CalciumStored in the boneOnly 1% of body Ca is in fluid spacesNl = 2.2-2.6 mmol/L50% is bound to albumin and other proteinthe other 50% is the free active formserum levels do not change with daily intake and excretionserum levels are controlled by parathyroid hormone, vit D and calcitoninthrough regulation of GI absorption, renal excretion, skeletal deposition or resorption.there is an inverse relationship with Po4

CalciumRelation to albuminlow serum albumin will result in low Ca lab valuesdoes not mean low ionized Caeach 10-gm/L change in albumin will change Ca by 0.2 mmol/l in the same direction

CalciumRelation to acid-base imbalancesacidosis more H are bound to albumin as an attempt to buffer displacement of Ca ions from binding sites increase free calciumthe opposite is true for alkalosisfor each 0.1 change in PH ionized Ca changes by 0.42 mmol/L in the opposite direction

Cancer72 yo female with stage 4, metastatic breast cancer.Patient is confused, cachetic, and nauseatedNa+= 147, Ca+2 = 14mg/dl

HYPERCALCEMIACancers associated with hypercalcemiabonebreastkidneycolonthyroidmultiple melanomaTreatmenthydrationdiuretics-lasixmithramycincorticosteroidscalcitonin- osteoclast resorptionphosphate

Hypercalcemiacorrected total Ca > 2.6 mmol/L or ionized ca > 1.15 mmol/LClinical manifestationssee table 9.10mental changes do not correlate with degree of hypercalcemia

General MeasuresManaging hypercalcemia will be directed at reducing bone resorption and increasing urinary excretion of calcium. Avoid immobilizationStop drugs which inhibit urinary calcium excretion e.g thiazides

Stop drugs which decrease renal blood flow e.g cimetidine, NSAIDsStop drugs containing:Calcium (Tums, Rolaids, etc.)Vitamin DVitamin A/ Retinoids

Hospital based Management1. For ALL patientsIntravenous fluids: Isotonic saline (0.9% NaCl) @ 300-400 ml/hr

For hypercalcemia 4 mmol/LIM/SC Calcitonin: 4-8 IU/kg q 6h x 2dPLUSIV Pamidronate (started concurrently with calcitonin): 90 mg in 250 mL NS over1 hourORIV Zoledronic acid (started concurrently with calcitonin): 4 mg in 100 mL NS over 15 minutes

For hypercalcemia 3.5 mmol/LIV Pamidronate: 90 mg in 250 ml NS over 1 hourORIV Zoledronic acid: 4 mg in 100 ml NS over 15 minutes

For hypercalcemia < 3.5 mmol/L with symptomsIV Clodronate 1500 mg in 500 ml NS over 4 hours , with observation over 48 hours; if no response then use Pamidronate or Zoledronic acid as aboveORIV Pamidronate 60-90 mg in 250 ml NS over 1 hourOR4.3. IV Zoledronic acid 4 mg in 100 ml NS over 15 minutes

For hypercalcemia unresponsive to other measuresIV Mithramycin (Plicamycin) 25 g/kg repeat in 48 hours if no response; 12.5 g/kg if pre-existing renal or hepatic dysfunction

B- Removing Ca from the BodyGiven First because they are faster and more effective in acute situations1-Furosamide 1 mg/kgK must be given to aviod hypokalemia

Post op patient42 year old female admitted to the ICU post op after undergoing a thyroidectomy for thyroid cancer.

She is complaining of peri-oral numbness and tingling. Her DTRs are hyperactive and her ECG has a prolonged QT interval.

HYPOCALCEMIAChvosteks sign - facial muscle spasmTrousseaus sign - carpal spasmTreatmentmonitor ECGIV calciumfollow up labsoral calcium supplements normal is 1 gram/day

HypocalcaemiaCorrected Ca < 2.2 mmol/LIonized Ca < 1 mmol/L

TreatmentA-Acute treatment:IV calcium 2.5-5 mmol Ca infusion 0.075 0.1 mmol Ca/kg/hrCaCL 6.8 mmol/gCa gluconate and glucoptate 2.3 mmol/gMonitoring parameters:Ca level to avoid hypercalcemiaBP, ECG to evaluate cardiac function

HypocalcaemiaPts with hypocalcaemia that does not resolve with replacement should be evaluated for hypomagnesaemia because their Sx are similarB- Chronic Treatmentcorrect underlying etiologymost common etiology is low Vit DLow levels of Vit Dappears in advanced hepatic or renal disease due to decreased activation into the active formTX: Ca and vitD replacement

HypocalcaemiaVIT D supplementationDose: ergocalciferol 1.25-5 mg/dayDihydrotachysterol 0.25-1 mg/dOnset of action several weeksEffect prolonged due to long half-lifeIn case of compromised renal or hepatic activation active form must be used.Calcifediol 25-200 mcg/dcalcitirol0.25-1 mcg/donset of action 3-7 daysshorter half-life less risk of hypercalcemiaCalcium supplementation;elemental Ca 25-100 mmol/d ( 1-4 g)Hypocalcaemia due to hypoparathyroidism is treated by parathyroid hormone replacement

Calcium salt

Content of elemental Ca

comments

Calcium carbonate

10.2 ( 400 mg)/ 1000 mg

Preferred because least No of tablets needed

Ca lactate

1.5 mmol (60 mg) / 300mg

Ca gluceptate

2.2 mmol (80 mg)/ 1000 mg

Ca gluconate

2.3 mmol ( 90 mg)/ 1000mg

Liq form of lactate and carbonate salts are sued for pts with achlohydria or H2anatgonist therapy because tablet dissolution will be incomplete without gastric acid

MagnesiumThe body contains 1000 mmol mg99% is in bone and ICF1% in vascular space 25 % is bound to proteins75% free and activeNl = 0.8-1.2 mmol/lAbnormal levels rarely appear isolated usually occur with other solute abnormalities

HypermagnesemiaMg >1.2 mmol/LSerious Sx do not appear until > 3 mmol/LCauses and symptoms:See table 9.11Large Mg loads can be excreted by the kidneyHyperMg rarely occurs without renal dysfunction esp. in pts using Mg antacids

HypermagnesemiaCausesExogenous ingestionImpaired renal excretion

Treatment: Eliminate exogenous source of Mg

Treatment:

removal from the body by peritoneal and hemodialysisshifting it back into ICF using glucose and insulin as in hyperkalmeia

HypomagnesaemiaMg < 0.8 mmol/lSx at , 0.6 mmol/lUsually appears with low K, Ca, and PO4These electrolytes should be measuredCauses and symptoms:See table 9.11

HypomagnesemiaCausesDecreased Intake Malnutrition AlcoholismDecreased AbsorptionIncreased Losses GI losses Renal losses

Hypomagnesemia4.Drug Induced Hypomagnesemiaa. GI Losses Laxativesb. Renal Losses Diuretics, cisplatin, aminoglycosides, amphotericin B

Replacement therapyIVMg sulfate 1 gm of 50% sol 4mmol mg. Mg< 0.6 0.25 mmol/kg/d Mg 0.7-1.2 0.15 mmol/kg/dGiven over 1-4 hrsLevels checked in 1-2 hrs after To give time for IC shiftOral:Oral replacement of large deficit is difficultMg is a saline cathartic large doses produce diarrheaUp to 20 mmol/d given in divided dosesUse Mg oxide tablets or Mg sulfate sol

Phosphorus99.99% contained in bone and ICFNL= 0.8-1.6 mmol/LFunction:Form high-energy phosphate bonds of ADP and ATP in glycolysis and Krebs cycleFacilitate the release of Oxygen from Hg

Hyperphosphatemia> 1.6 mmol/lalmost always due to decreased excretion due to renal dyfxit causes reciprocally hypocalcaemiahigh phosphate levels do not in it cause significant physiological consequences.Causes and symptomssee table 9.12

HyperphosphatmeiaCausesRenal impairmentIncreased intake

Treatment Phosphate binders: Alternagel, Amphojel, Calcium Suppliments

TreatmentReduce GI absorption by precipitating with AL containing antacidsGlucose insulinHemodialysis used in hypocalemia but not very efficient

Hypophosphatemia< 0.8 mmol/lSx < 0.3 mmol/lCauses and symptomsSee table 9.12

HypophosphatmeiaCausesImpaired absorptionAluminum or calcium bindingRedistribution Respiratory alkalosis Glucose + insulinIncreased Excretion

TreatmentReplacement with Na or K phosphate saltsReplacement should be slow to prevent Caphospate PPT, renal failure and hyperphospatemia.Dose:Po4 < 0.3 0.3-0.6 mmol/kg/dPo4 0.4-0.8 0.2-0.3 mmol/kg/dGiven over at least 6hrs to allow equilibrationCheck serum levels 3-4 hrs after dose

Normal Laboratory ValuesSodium135-145 meq/LPotassium 3.5-5.0 meq/LChloride95-105 meq/LBicarbonate22-28 meq/LCalcium9-11 mg/dLPhosphate3.2-4.3 mg/dLGlucose70-110 mg/dLBUN8-18 mg/dLCreatinine0.6-1.2 mg/dLOsmolality (P)280-295 mOsm/kgOsmolality (U)50-1200 mOsm/kg

****************************************************************The signs of volume depletion or overload can be subtle. Note that some appear in both columns - especially tachycardia. Postural hypotension, where blood pressure falls on standing or sitting up is a reliable early sign of hypovolaemia, which is often not checked. ***********************************************************************************************