Oxford Handbook of Critical Care - part 3 ppsx

See also: Pul monary artery catheter—use, p118; Cardi ac output—other invasive, p124; Cardi ac output—non-i nvasi ve 1, p146; Cardiac output—non-invasive 2, p146; Fluid challenge, p274;

Insert catheter 15cm (i.e beyond the length of the introducer sheath) before i nfl ati ng bal loon Advance cathetersmoothl y through the right heart chambers Pause to record pressures and note waveform shape i n RA, RV and

PA When a characteri sti c PAWP waveform is obtai ned, stop advancing catheter, defl ate balloon and ensure that

PA waveform reappears If not, withdraw catheter by a few cm

Complications

Problems of central venous catheteri sationArrhythmi as (especial ly when traversing tricuspid val ve)Infection (i ncl udi ng endocardi ti s)

Pul monary artery rupturePul monary infarcti onKnotti ng of catheterVal ve damage (do not wi thdraw catheter unless bal loon deflated)

Troubleshooting

Excessive catheter l ength i n a heart chamber causes coil ing and a ri sk of knotti ng No more than 15–20cm should be

passed before the waveform changes If not, deflate ball oon, withdraw catheter, repeat A knot can be managed by

(i) ‘unknotting’ with an intraluminal wire, (ii ) pull ing taut and removing catheter + introducer sheath together, or

(ii i) surgi cal or angiographi c i ntervention

If catheter fai ls to advance to next chamber, consi der ‘stiffening’ catheter by i njecti ng iced crystalloid through distal

lumen, roll ing patient to left l ateral position or advanci ng catheter slowly wi th bal loon defl ated

The catheter shoul d never be wi thdrawn with the bal loon i nfl ated

Arrhythmias on inserti on usuall y occur when the catheter ti p is at the tricuspi d val ve These usuall y resolve on

withdrawi ng the catheter or, occasi onal ly, after a sl ow bolus of 1.5mg/kg l idocai ne

Waveforms

Thermodil ution is the technique uti li sed by the pulmonary artery catheter to measure right ventri cul ar cardi ac output.

The principle is a modi ficati on of the Fi ck pri nci pl e whereby a bolus of cooled 5% glucose is injected through the

proximal lumen into the central circul ation (right atri um) and the temperature change is detected by a thermistor at

the catheter ti p, some 30cm di stal A modi fi cation of the Hamil ton–Stewart equation, util ising the volume,

temperature and speci fic heat of the injectate, enables cardiac output to be calculated by an on-li ne computer from a

curve measuring temperature change i n the pul monary artery

Continuous thermodil uti on measurement uses a modifi ed catheter that emits heat pulses from a thermal filament

lyi ng withi n the right ventri cl e and right atrium, 14–25cm from the ti p 7.5W of heat are added to the bl ood

intermittently every 30–60s and these temperature changes are measured by a thermi stor 4cm from the ti p Though

updated frequently, the cardiac output displ ayed i s usually an average of the previous 3–6min

Thermodilution injection technique

The computer constant must be set for the vol ume and temperature of the 5% gl ucose used 10ml of i ce-col d glucose

provides the most accurate measure 5ml of room temperature i njectate is suffi cientl y precise for normal and hi gh

output states however its accuracy does worsen at l ow output val ues

Press ‘Start’ button on computer

Non-continuous (by injection technique)

5–10% i nter- and intraobserver variabil ity

Erroneous readi ngs wi th tri cuspi d regurgi tation, intracardiac shunts

Frequentl y repeated measurements may result in consi derabl e volumes of 5% gl ucose bei ng i njected

See also:

Pul monary artery catheter—use, p118; Cardi ac output—other invasive, p124; Cardi ac output—non-i nvasi ve (1), p146;

Cardiac output—non-invasive (2), p146; Fluid challenge, p274; Hypotension, p312; Heart fail ure—assessment, p324;

Systemic inflammation/multi-organ fail ure, p484; Burns—fl uid management, p510

Cardiac output—other invasive

Dye dilution

Mixing of a given vol ume of indicator to an unknown volume of fluid all ows calculation of this vol ume from the degree

of indicator di lution The ti me elapsed for the indicator to pass some distance in the cardi ovascular system yiel ds a

P.126

cardi ac output val ue, calculated as:

…where I is the amount of indicator injected, Cm is the mean concentration of the i ndi cator and t is the total duration

of the curve The traditional dye di lution technique is to inject indocyanine green into a central vein fol lowed by

repeated sampli ng of arteri al bl ood to enable constructi on of a ti me–concentrati on curve with a rapid upstroke and an

exponenti al decay Pl otting the dye decay curve semi logarithmicall y and extrapolating values to the origi n produces

the cardi ac output The COLD-Pulsion device measures the concentrati on decay directly from an indwell ing arterial

probe, thus computing cardiac output Alternati vel y, this device may use the thermodil ution approach, avoiding

pul monary artery catheteri sation The LiDCO device is based on a similar pri nci ple using li thium as the ‘dye’

Advantages

Reasonabl y accurate, less i nvasive than pulmonary artery catheter placement

Disadvantages

Invasi ve, reci rculation of dye prevents multipl e repeated measurements, lengthy, underestimates low output values

Inaccurate with moderate/ severe val vul ar regurgitati on Use of paral ysi ng agents may i nterfere with l ithium

measurement

Direct Fick

The amount of substance passing i nto a flowing system i s equal to the difference i n concentration of the substance on

each side of the system mul tiplied by the flow wi thin the system Cardiac output i s thus usually calculated by

dividing total body oxygen consumpti on by the di fference i n oxygen content between arterial and mixed venous

blood Al ternatively, CO2 production can be used instead of VO2 as the indicator Arterial CO2 can be derived

non-invasively from end-tidal CO2 whi le mi xed venous CO2 can be determi ned by rapid rebreathing i nto a bag until

CO2 level s have equil ibrated

Advantages

‘Gold standard’ for cardiac output estimation

Disadvantages

For VO2: Invasi ve (requires measurement of mixed venous blood), requires l eak-free open ci rcuit or an unwieldy

cl osed ci rcuit technique Oxygen consumption measurements via metabol ic cart unrel iable if FIO2 i s high Lung

oxygen consumption not measured by pulmonary artery catheter techni que (may be high i n ARDS, pneumoni a…)

For CO2: Non-invasi ve but requi res normal lung function and is thus not generally appli cable in ICU patients

See also:

CO2 monitori ng, p92; Blood gas analysis, p100; Extravascul ar lung water measurement, p104; Pulmonary artery

catheter—use, p118; Cardiac output—thermodil uti on, p122; Cardiac output—non-invasive (1), p126; Cardiac

output—non-i nvasive (2), p128; Indirect calorimetry, p168; Fl uid chall enge, p274; Hypotensi on, p312; Heart

fai lure—assessment, p324; Systemi c i nfl ammati on/mul ti-organ fai lure, p484; Burns—flui d management, p510

Cardiac output—non-invasive (1)

Doppler ultrasound

An ul trasound beam of known frequency is reflected by movi ng red bl ood corpuscl es with a shift i n frequency

proporti onal to the blood flow velocity The actual velocity can be calculated from the Doppl er equati on whi ch

requi res the cosi ne of the vector between the di rection of the ultrasound beam and that of blood flow Thi s has been

appli ed to blood flow in the ascendi ng aorta and aorti c arch (via a suprasternal approach), descending thoracic aorta

(oesophageal approach) and i ntracardiac fl ow (e.g transmi tral from an apical approach) Spectral anal ysi s of the

Doppler frequency shi fts produces velocity–time waveforms, the area of which represents the ‘stroke di stance’, i.e

the di stance travell ed by a column of blood wi th each l eft ventricular systole (see figure opposite) The product of

stroke di stance and aortic (or mi tral val ve) cross-secti onal area is stroke volume Cross-secti onal area can be

measured echocardi ographicall y; however, as both operator expertise and equi pment is requi red, this addi tional

measurement can be ei ther i gnored or assumed from nomograms to provide a reasonabl e estimate of stroke volume.

Advantages

Qui ck, safe, mi nimall y i nvasi ve, reasonabl y accurate, conti nuous (vi a oesophageal approach), other i nformati on on

contractili ty, prel oad and afterload from waveform shape (see fi gure opposite)

Disadvantages

Non-conti nuous (unless via oesophagus), learning curve, operator dependent

Echocardiography

Combines structural as wel l as dynamic assessment of the heart usi ng ultrasound reflected off various interfaces

Transthoracic or transoesophageal probes provide i nformation on valve i ntegri ty, gl obal (diastoli c and systol ic) and

P.128

regional ventricular function, wall thickness, pericardial fl ui d or thickening, aortic di ssecti on, ventricular volumes and

ejecti on fracti on, and pulmonary pressures Often combined with integral Doppler ul trasound for cardi ac output

estimati on derived from combined measurement of aortic di ameter pl us flow at vari ous si tes, e.g left ventri cul ar

outflow tract, aorta, transmi tral Analytic software or formul ae can al so enable computation of cardi ac output from

estimati ons of ventri cular volumes

Advantages

Non-invasive, safe, relatively quick Provides other useful informati on on cardiac structure and function

Disadvantages

Expensive equipment, lengthy l earning curve and interobserver vari abili ty Body habitus or pathology (e.g

emphysema) may i mpair image quality

Doppler blood flow velocity waveform variables

Figure No Caption Available.

Changes in Doppler flow velocity waveform shape

Figure No Caption Available.

See also:

Cardiac output—thermodi lution, p122; Cardi ac output—other invasive, p124; Cardiac output—non-i nvasi ve (2), p128;

Fluid chall enge, p274; Hypotension, p312; Heart fai lure—assessment, p324; Systemic i nfl ammati on/multi-organ

fai lure, p484; Burns—fluid management, p510

Cardiac output—non-invasive (2)

Pulse contour analysis

The concept of thi s technique is that the contour of the arteri al pressure waveform is proporti onal to stroke vol ume

However, it is also i nfl uenced by aorti c i mpedance so another cardiac output measuri ng techni que (e.g commerci al

devices uti lising COLD-Pul si on or LiDCO) must be used i n tandem for ini ti al cal ibration Although i t can then be used

as a means of conti nuous cardi ac output monitori ng, frequent re-calibration should be performed against the

reference technique Thi s i s particul arl y i mportant when changes in impedance occur, e.g wi th changes i n cardiac

Changes i n vascular compliance wi ll affect accuracy requi ri ng frequent recali brati on Requi res a good quali ty,

non-obstructed and non-damped arteri al waveform There is debate about the relative qual ity of si gnal from radial vs

femoral artery

Thoracic bioimpedance

Impedance changes ori ginate in the thoraci c aorta when bl ood is ejected from the l eft ventricle This effect is used to

determine stroke volume from formulae util isi ng the el ectri cal fi eld si ze of the thorax, baseli ne thoracic impedance

and fl uctuation related to systol e, and ventricular ejection time A correction factor for sex, height and wei ght is al so

introduced The technique simply utili ses four pai rs of el ectrodes placed in proscri bed positions on the neck and

thorax; these are connected to a dedi cated monitor which measures thoraci c impedance to a l ow ampl itude, high

(70kHz) frequency 2.5mA current appl ied across the electrodes

Advantages

Qui ck, safe, total ly non-invasive, reasonably accurate in normal, spontaneousl y breathi ng subjects

Disadvantages

Di screpanci es in criti cal ly il l pati ents (especi all y those with arrhythmias, tachycardias, i ntrathoraci c flui d shi fts,

anatomical deformi ti es, aorti c regurgi tation), metal withi n the thorax, inabi li ty to verify si gnal

See also:

Cardiac output—thermodi lution, p122; Cardi ac output—other invasive, p124; Cardiac output—non-i nvasi ve (1), p126;

Fluid chall enge, p274; Hypotension, p312; Heart fai lure—assessment, p324; Systemic i nfl ammati on/multi-organ

fai lure, p484; Burns—fluid management, p510

Gut tonometry

A gas permeable si li cone ball oon attached to a sampling tube is passed i nto the l umen of the gut Devi ces exist for

tonometry in the stomach or si gmoid col on The tonometer all ows indirect measurement of the PCO2 of the gut

mucosa and calculati on of the pH of the mucosa

Indications

Gut mucosal hypoperfusion i s an earl y consequence of hypovolaemi a Covert ci rculatory i nadequacy due to

hypovolaemia may be detected as gut mucosal acidosis and has been related to post-operati ve compli cations after

major surgery In cri ti cal ly il l pati ents there i s some evidence that prevention of gut mucosal acidosi s i mproves

outcome The si gmoid col on tonometer is useful to detect ischaemic coli tis early (e.g after abdomi nal vascular

surgery)

Technique

Saline tonometry

In the origi nal technique the tonometer ball oon was prepared by degassing and fil li ng with 2.5ml 0.9% sal ine The

sal ine was withdrawn into a syringe connected to the sampling tube prior to inserti on After inserti on the saline was

passed back into the bal loon The PCO2 of the sal ine in the ball oon equil ibrated with the PCO2 of the gut l umen over a

period of 30–90min At steady state it was assumed that the PCO2 of the gut l umen and gut mucosa were i n

equil ibrium Time correction factors were deri ved for parti al equil ibration between the bal loon sali ne and the gut

lumen The measurement was completed by sampli ng the saline from the ball oon and an arterial blood sample for

measurement of arteri al [HCO3-]

Gas tonometry

Usi ng air i n the tonometry bal loon all ows more rapi d equi li bration between the tonometer and the luminal PCO2 A

modifi ed capnometer automatically fi ll s the bal loon wi th ai r and samples the PCO2 after 5–10min equil ibration

Subsequent cycl es of bal loon fil ling do not use fresh ai r so CO2 equil ibrati on is quicker Tonometric PCO2 may be

compared with end-tidal PCO2 (measured with the same capnometer) as an estimate of arteri al PCO2 With a normal

capnogram, a balloon PCO2 si gnifi cantly hi gher than end-tidal PCO2 i mpl ies gut mucosal hypoperfusi on

pH versus regional PCO2

The pH of the gut mucosa (pHi) may be cal cul ated usi ng a modified Henderson–Hasselbach equation:

where K i s the time dependent equi li bration constant However, most of the vari ati on in the measurement is due to

variation i n regi onal PCO2 Comparing regional PCO2 with PaCO2 gi ves as much informati on as making the calculati on

CO2 monitori ng, p92; Blood gas analysis, p100

Ovid: Oxford Handbook of Critical Care

Editors: Singer, Mervyn; Webb, Andrew R.

Title: Oxford Handbook of Critical Care, 2nd Edition

Copyri ght ©1997,2005 M Si nger and A R Webb, 1997, 2005 Publ ished in the United States by Oxford Universi tyPress Inc

> Table of Co ntents > Neu rological Mo nitoring

Neurological Monitoring

Intracranial pressure monitoring

Indications

To confirm the diagnosis of raised i ntracranial pressure (ICP) and monitor treatment May be used i n cases of head

injury particularly if ventil ated, Gl asgow Coma Score ≤8, or wi th an abnormal CT scan Also used in encephal opathy,

post-neurosurgery and in selected cases of intracrani al haemorrhage Al though a rai sed ICP can be rel ated to poor

prognosi s after head injury, the converse is not true Sustained reduction of raised ICP (or mai ntenance of cerebral

perfusion pressure) i n head injury may improve outcome although large controll ed tri al s are lacking

Methods of monitoring intracranial pressure

Ventricular monitoring

A catheter i s inserted into the lateral ventri cle vi a a burr hol e The catheter may be connected to a pressure

transducer or may contai n a fi breoptic pressure monitori ng device Fibreopti c catheters require regular cali brati on

according to the manufacturer's instructions Both systems shoul d be tested for patency and damping by temporaril y

rai si ng intracranial pressure (e.g wi th a cough or by occl udi ng a jugular vein) CSF may be drained through the

ventri cular catheter to reduce i ntracranial pressure

Subdural monitoring

The dura is opened vi a a burr hol e and a hollow bolt inserted i nto the skul l The bol t may be connected to a pressure

transducer or admi t a fi breoptic or hi -fi del ity pressure moni toring device A subdural bol t i s easi er to insert than

ventri cular monitors The mai n disadvantages of subdural monitori ng are a tendency to underesti mate ICP and

damping effects Agai n cali brati on and patency testing should be performed regul arl y

Complications

Infection—particularly after 5 days

Haemorrhage—particul arl y with coagulopathy or difficult insertion

Using ICP monitoring

Normal ICP i s <10mmHg A raised ICP i s usuall y treated when >25mmHg in head injury As ICP increases, there are

often sustai ned ri ses i n ICP to 50–100mmHg lasti ng for 5–20min, increasing wi th frequency as the basel ine ICP rises

Thi s i s associ ated with a 60% mortal ity Cerebral perfusion pressure (CPP) is the di fference between mean BP and

mean ICP Treatment ai med at reducing ICP may also reduce mean BP It i s i mportant to mai ntain CPP >50–60mmHg

See also:

Intracranial haemorrhage, p376; Subarachnoi d haemorrhage, p378; Raised intracranial pressure, p382; Head injury

(1), p504; Head injury (2), p506

Jugular venous bulb saturation

Retrograde passage of a fibre-opti c catheter from the i nternal jugular vein into the jugul ar bul b enables conti nuous

monitori ng of jugular venous bulb saturati on (SjO2) This can be used in conjuncti on with other moni tors of cerebral

haemodynamics such as mi ddl e cerebral blood flow, cerebral arteri ovenous lactate di fference and intracranial

pressure to di rect management

Principles of SjO2 management

Normal values are approximatel y 65–70% In the absence of anaemia and with maintenance of normal SaO2 values,

val ues of SjO2 >75% suggest luxury perfusi on or global infarcti on with oxygen not bei ng utili sed; values <54%

correspond to cerebral hypoperfusion whil e values <40% suggest global ischaemi a and are usual ly associ ated with

P.138

increased cerebral l actate producti on Knowl edge of SjO2 allows optimi sation of brai n bl ood fl ow to avoi d (i) either

excessive or inadequate perfusion and (i i) iatrogenicall y i nduced hypoperfusi on through treating raised intracranial

pressure aggressi vel y with di ureti cs and hyperventil ati on Studi es in trauma pati ents have found (i) a higher

mortal ity wi th epi sodes of jugular venous desaturation and (ii) a significant rel ationshi p between cerebral perfusion

pressure (CPP) and SjO2 when the CPP was <70mmHg A fall ing SjO2 may be an i ndi cation to increase CPP though no

prospective randomised tri al has yet been performed to study the effect on outcome

Approximatel y 85% of cerebral venous drainage passes down one of the i nternal jugular veins (usually the right)

SjO2 usuall y represents drainage from both hemi spheres and i s equal on both si des; however, after focal i njury, this

pattern of drai nage may alter

If the catheter is si ted too l ow in the jugul ar bul b, erroneous SjO2 values may resul t from mi xing of i ntracerebral and

extracerebral venous blood This could be parti cul arl y pertinent when cerebral blood flow is low

Ensure l ight i ntensi ty readi ng i s satisfactory; i f too high the catheter may be abutti ng against a wall, and i f l ow the

catheter may not be patent or have a smal l clot over the tip Before treating the patient, always confi rm the veracity

of low readi ngs against a blood sampl e drawn from the catheter and measured i n a co-oximeter

Formulae

where SjO2 = jugular bulb oxygen saturation

SaO2(%) = arterial oxygen saturation CMRO2 = cerebral metabolism of oxygen CBF = cerebral blood flow

cerebral perfusion pressure =mean systemi c BP -i ntracranial pressure

See also:

Intracranial pressure moni toring, p134; Other neurol ogi cal moni toring, p140; Intracranial haemorrhage, p376;

Subarachnoi d haemorrhage, p378; Raised i ntracranial pressure, p382; Head i njury (1), p504; Head injury (2), p506

EEG/CFM monitoring

EEG monitoring

The EEG refl ects changes in cortical electrical function Thi s, in turn, is dependent on cerebral perfusi on and

oxygenati on EEG moni toring can be useful to assess epilepti form acti vi ty as well as cerebral well -bei ng in patients

who are sedated and paral ysed The conventi onal EEG can be used i ntermittently but data reduction and artefact

suppression are necessary to all ow successful use of EEG recordings in the ICU

Bispectral index (BIS) monitor

BIS i s a stati sti cal i ndex deri ved from the EEG and expressed as a score between 0 and 100 Scores bel ow 50 have

been reli abl y associ ated wi th anaesthesia-induced unconsciousness Assessment in the cri ticall y i ll patient may be

compli cated by various confounding factors such as septi c encephal opathy, head trauma and hypoperfusion A l ow

score is related to deep or excessive sedation, and may al low dose reduction (or cessati on) of sedative agents,

especi al ly in paralysed patients

Cerebral function monitor (CFM)

The CFM is a si ngl e channel , fi ltered trace from 2 recording el ectrodes pl aced over the parietal regi ons of the scal p A

thi rd el ectrode may be used in the midl ine to help with i nterference detection The parietal recording electrodes are

usuall y placed cl ose to watershed areas of the brai n i n order to allow maxi mum sensi tivity for i schaemia detection

Vol tage i s displayed against time on a chart runni ng at 6–30cm/h

Figure No Caption Available.

Use of CFM

The CFM may detect cerebral ischaemia; burst suppressi on (periods of i ncreasingly prol onged electrical sil ence)

provide an earl y warning

Sedati on produces a fall i n basel ine to <5µV, equi val ent to burst suppression This i s equi val ent to maximum

reduction i n cerebral VO2 and no further benefit would be gai ned from addi ti onal sedation

Sei zure activi ty may be detected in patients despi te apparentl y adequate cl inical control or where muscl e rel axants

have been used

Typical CFM patterns

Figure No Caption Available.

Other neurological monitoring

Cerebral blood flow (CBF)

CBF can be measured by radioisotopic techniques uti li sing tracers such as xenon-133 gi ven intravenously or by

inhal ati on This remains a research tool in view of the radi oacti vity exposure and the usual need to move the patient

to a gamma-camera However, portabl e moni tors are now avail abl e Middle cerebral artery (MCA) blood flow can be

determined non-invasi vel y by transcrani al Doppl er ultrasonography The pul satil ity index (PI) relates to

cerebrovascular resi stance wi th a rise i n PI i ndi cating a rise i n resistance and cerebral vasospasm

Vasospasm can also be designated when the MCA blood flow velocity exceeds 120cm/s and severe vasospasm when

vel oci ti es >200cm/s Low values of common carotid end-diastol ic bl ood fl ow and vel oci ty have been shown to be

highl y di scriminati ng predictors of brai n death Impaired reacti vi ty of CBF to changes i n PCO2 (in normal s 3–5% per

mmHg PCO2 change) i s another marker of poor outcome

Near-infra red spectroscopy (NIRS)

Near-infrared (700–1000nm) l ight propagated across the head i s absorbed by haemoglobin (oxy- and de-oxy),myoglobin and oxidi sed cytochrome aa3 (the terminal part of the respiratory chain involved in oxi dative

phosphoryl ation)

The sum of (oxy- + deoxy-) haemogl obi n i s considered an index of cerebral bl ood volume (CBV) change, and thedifference as an index of change in haemoglobin saturati on assumi ng no variation occurs in CBV CBV and fl owcan be quanti fied by changing the FIO2 and measuring the response

Cerebral blood flow is measured by a modi fi cation of the Fi ck pri ncipl e Oxyhaemogl obi n is the intravascul arnon-diffusibl e tracer, i ts accumulation being proportional to the arterial i nfl ow of tracer Good correl ations havebeen found wi th the xenon-133 technique

Cytochrome aa3 cannot be quanti fied by NIRS but i ts redox status may be foll owed to provi de some i ndi cation ofmitochondrial function

Movement artefact must be avoided and some devices requi re reduction of ambient lighti ng

Lactate

The brain normall y util ises l actate as a fuel; however, i n states of severely impaired cerebral perfusion the brai n may

become a net lactate producer with the venous lactate rising above the arterial value A l actate oxygen i ndex can be

derived by divi di ng the venous–arterial l actate di fference by the arterio-jugular venous oxygen difference Val ues

>0.08 are consi stentl y seen wi th cerebral ischaemi a

See also:

Lactate, p170; Intracranial haemorrhage, p376; Subarachnoi d haemorrhage, p378; Raised intracranial pressure,

p382; Head i njury (1), p504; Head injury (2), p506; Brain stem death, p548

Ovid: Oxford Handbook of Critical Care

Editors: Singer, Mervyn; Webb, Andrew R.

Title: Oxford Handbook of Critical Care, 2nd Edition

Copyri ght ©1997,2005 M Si nger and A R Webb, 1997, 2005 Publ ished in the United States by Oxford Universi tyPress Inc

> Table of Co ntents > Laborator y M onitor ing

Laboratory Monitoring

Urea and creatinine

Measured in blood, urine and, occasi onall y, i n other fluids such as abdomi nal drain fl uid (e.g ureteric di sruption,

fistulae)

Urea

A product of the urea cycle resul ti ng from ammonia breakdown, i t depends upon adequate l iver function for its

synthesi s and adequate renal function for its excreti on Low level s are thus seen in ci rrhosis and hi gh levels i n renal

fai lure Uraemi a i s a cl inical syndrome i ncl uding lethargy, drowsiness, confusi on, pruritus and pericardi ti s resulting

from high pl asma l evels of urea (or, more correctly, nitrogenous waste products—azotaemia)

The ratio of urine:pl asma urea may be useful i n distingui shi ng oli guria of renal or pre-renal origins Higher ratios

(>10:1) are seen in pre-renal conditi ons, e.g hypovolaemi a, whereas low l evels (<4:1) occur with direct renal

causes

24-h measurement of urinary urea (or nitrogen) excretion has been previously used as a guide to nutriti onal protei n

replacement but is currently not consi dered a useful routine tool

Creatinine

A product of creatine breakdown, it is predominantl y derived from skeletal muscl e and i s also renal ly excreted Low

levels are found with malnutri ti on and hi gh l evels wi th muscle breakdown (rhabdomyol ysi s) and impai red excretion

(renal failure) In the latter case, a creati ni ne value >120 µmol/l suggests a creatini ne cl earance <25ml /mi n

The usual rati o for plasma urea (mmol /l ) to creatinine (µmol/l) is approximatel y 1:10 A much lower ratio in a

criti cal ly il l pati ent is suggestive of rhabdomyolysis whereas higher ratios are seen in ci rrhosis, malnutriti on,

hypovolaemia and hepatic fai lure

The ratio of urine:pl asma creatinine may help di sti nguish between oli guria of renal or pre-renal origins Higher ratios

(>40) are seen i n pre-renal conditions and low level s (<20) wi th di rect renal causes

Creati ni ne clearance is a measure of gl omerul ar fil trati on Once fil tered, only small amounts of creatinine are

reabsorbed Normal ly it exceeds 100ml/min

Normal plasma ranges

P.146

Urea 2.5–6.5mmol/l Creatinine 70–120µmol/l (depends on lean body mass)

See also:

Haemo(dia)fil trati on (1), p62; Haemo(dia)fi ltration (2), p64; Peritoneal di alysis, p6; Nutrition—use and indicati ons;

Uri nal ysis, p166; Acute failure renal fai lure—diagnosis, p332; Acute renal fail ure—management, p334;

Rhabdomyol ysis, p528

Electrolytes (Na+, K+, Cl-, HCO3 -)

Measured accuratel y by direct-readi ng i on-speci fic el ectrodes from plasma or uri ne, though are sensitive to

interference by excess l iquid heparin

Sodium, potassium

Plasma level s may be elevated but poorly reflect intracel lul ar (approximately 3–5mmol/l for Na+, 140–150mmol/l for

K+) or total body l evels Pl asma potassi um level s are affected by plasma H+ levels; a metaboli c acidosi s reduces

uri nary potassium excretion whil e an al kal osis wil l i ncrease excretion

Ol der measuring devi ces such as flame photometry or indi rect-reading ion-specifi c electrodes gave spuri ously low

plasma Na+ l evels with concurrent hyperproteinaemi a or hypertrigl yceri daemia

Uri nary excretion depends on i ntake, total body bal ance, aci d–base bal ance, hormones (incl udi ng anti–diureti c

hormone, aldosterone, corti costeroi ds, atrial natriuretic pepti de), drugs (particularly di ureti cs, non-steroidal

anti-i nfl ammatori es and ACE inhi bitors), and renal function

In oli guria, a urinary Na+ level <10mmol /l suggests a pre-renal cause whereas >20mmol/l i s seen wi th direct renal

damage This does not apply if di uretics have been given previousl y

Chloride, bicarbonate

Bi carbonate level s vary with aci d–base bal ance

In the ki dney, Cl- reabsorption i s i ncreased when HCO3- reabsorption i s decreased, and vice versa Plasma [Cl-] thus

tends to vary i nversely with plasma [HCO3-], keeping the total anion concentration normal A rai sed [Cl-] (producing

a hyperchloraemic metabolic acidosi s) may be seen wi th administration of large volumes of isotonic sal ine or i sotoni c

sal ine-containing colloid sol utions Hyperchloraemia is al so found with experimental sal t water drowning but rarely

seen i n actual cases

Anion gap

The anion gap i s the difference between unesti mated ani ons (e.g phosphate, ketones, l actate) and cations

In metabolic acidosi s an i ncreased ani on gap occurs with renal failure, ingesti on of acid, ketoaci dosis and

hyperl actataemi a, whereas a normal anion gap (usuall y associ ated wi th hyperchl oraemi a) i s found with decreased

aci d excreti on (e.g Addison's disease, renal tubular acidosi s) and loss of base (e.g diarrhoea, pancreati c/bili ary

fistula, acetazol ami de, ureterosigmoidostomy)

Normal plasma ranges

Sodium 135–145mmol/l Potassium 3.5–5.3mmol/l Chloride 95–105mmol/l Bicarbonate 23–28mmol/l Anion gap = plasma [Na+] + [K+] - [HCO3-] - [Cl-]

Haemo(dia)fil trati on (1), p62; Haemo(dia)fi ltration (2), p64; Peritoneal di alysis, p66; Nutri tion—use and indicati ons,

p78; Urinalysi s, p166; Crystal loi ds, p176; Di uretics, p212; Tachyarrhythmias, p316; Bradyarrhythmi as, p318; Acute

renal fai lure—diagnosis, p332; Acute renal fail ure—management, p334; Vomi ti ng/gastri c stasis, p338; Diarrhoea,

p340; Acute li ver fai lure, p360; Hypernatraemi a, p416; Hyponatraemia, p418; Hyperkal aemia, p420; Hypokalaemia,

p422; Metabol ic acidosis, p434; Metaboli c alkalosis, p436; Di abetic ketoacidosi s, p442; Hyperosmol ar diabetic

emergenci es, p444; Hypoadrenal crisi s, p448; Poisoni ng—general pri nci ples, p452; Rhabdomyolysis, p528

Calcium, magnesium and phosphate

Calcium

Plasma calci um levels have been traditi onall y corrected to plasma al bumin levels; this is now considered irrelevant,

parti cul arl y at the low al bumin levels seen in cri ti cal ly il l pati ents Measurement of the ionised fracti on is now

consi dered more perti nent since it is the ioni sed fraction that is responsible for the extracell ular acti ons of calci um,

with changes in the i oni sed fraction being responsibl e for the symptomatol ogy

High cal cium l evels occur with hyperparathyroidism, certai n mali gnanci es and sarcoidosi s whil e l ow levels are seen in

renal fai lure, severe pancreatitis and hypoparathyroi dism

Magnesium

Plasma level s poorly reflect i ntracell ul ar or whol e body stores, 65% of whi ch is in bone and 35% in cells The ionised

fracti on is approximately 50% of the total level

High magnesi um levels are seen wi th renal fai lure and excessive administration; thi s rarely requires treatment unless

serious cardiac conduction probl ems or neurological compli cations (respi ratory paral ysi s, coma) intervene

Low level s occur foll owi ng severe di arrhoea, diuretic therapy, al cohol abuse, and accompany hypocal caemia

Magnesium is used therapeuticall y for a number of conditi ons i ncl udi ng ventri cular and supraventricular arrhythmias,

ecl ampsi a, sei zures, asthma and after myocardial i nfarction Supranormal plasma levels of 1.5–2.0mmol /l are often

sought

Phosphate

High l evels are seen with renal fail ure and i n the presence of an ischaemic bowel Low l evels (sometimes

<0.1mmol/l) occur with critical ill ness, chronic alcoholi sm and diuretic usage and may possibl y result in muscl e

weakness, fai lure to wean and myocardial dysfunction

Normal plasma ranges

Calcium 2.2–2.6mmol/l Ionised calcium 1.05–1.2mmol/l Magnesium 0.7–1.0mmol/l Phosphate 0.7–1.4mmol/l

See also:

IPPV—assessment of weani ng, p18; Plasma exchange, p68; Nutrition—use and indicati ons, p78; Tachyarrhythmias,

p316; Pancreati tis, p354; General ised seizures, p372; Hypomagnesaemi a, p424; Hypercalcaemia, p426;

Hypocalcaemi a, p428; Hypophosphataemi a, p430; Pre-eclampsi a and ecl ampsia, p538

Cardiac function tests

The importance of biochemical markers of myocardial necrosis has been emphasised by a consensus document from

the European Society of Cardiology and American Col lege of Cardi ology The diagnosis of myocardial i nfarction was

redefi ned as a typical rise and fall i n troponi n, or a more rapid ri se and fal l in CK-MB, with at l east one of the

fol lowing:

Ischaemic symptomsDevelopment of pathological Q waves on ECGECG ST elevation or depressi on

Coronary i nterventi on

Troponins

Troponins are bound to the actin fil ament within muscl es and are i nvolved i n exci tation–contraction coupli ng Both

cardi ac troponin T and troponin I are coded by specifi c genes and are immunologicall y distinct from those i n skel etal

muscl e Neither i s detectable in normal heal thy individual s but both are rel eased i nto the bloodstream from

cardi omyocytes damaged by necrosi s, toxins and i nfl ammati on They become detectabl e by 4–6h after myocardial

injury, peak at 14–18h, and persi st for up to 12 days Current assays are hi ghl y specific as they use recombi nant

human cardiac tropinin T as a standard

Due to their hi gh sensi tivity, plasma levels ri se wi th other cardiac i nsults, e.g tachycardi a (SVT/VT), pericardi ti s,

myocarditis, sepsis, heart failure, severe exertion and pul monary embol ism The degree of rise post-MI or during

criti cal i llness correlates wi th a worse outcome

A posi ti ve test i s when the cardiac troponin T or I value exceeds the 99th percenti le of values for a control group on

≥1 occasi on during the first 24h after the i ndex cl inical event For cardi ac troponin T this i s quoted as 0.05–0.1ng/ml

though many labs now consider val ues >0.03ng/ml as posi tive Val ues for cardiac troponi n I depend on the particular

assay used (usuall y >0.5–1.5ng/ml) The negati ve predictive value after an acute MI is probabl y strongest after 6h

Sensi tivity peaks at 12h but at the expense of a lower specificity With renal dysfunction, higher level s are needed to

diagnose myocardial damage due to impaired excretion

Cardiac enzymes

Creati ne kinase (CK) i s detectable in pl asma within a few hours of myocardial i njury The cardi ac-speci fic isoform

(CK-MB) can be measured i f there i s concurrent skeletal muscl e i njury CK and aspartate ami notransferase (AST)

peak by 24h and fal l over 2–3 days whereas the ri se and subsequent fall i n pl asma l actate dehydrogenase takes 1–2

days l onger

Brain (or B-type) natriuretic peptide (BNP)

Cardiomyocytes produce and secrete cardiac natri ureti c peptides Plasma level s rise i n a variety of conditi ons but

high l evels are predominantly associated with heart fail ure, and increase in rel ati on to severi ty A sensi tivity of

90–100% i s clai med, whereas speci ficity i s approxi mately 70–80% Numerous commercial assays for B-type

natri uretic pepti de (BNP) or proBNP are now avai lable, each with thei r own diagnosti c range They are useful as a

screening tool for pati ents presenting wi th dyspnoea, for prognosticati on, and for titration of therapy Level s rise i n

the el derly, i n renal fail ure, and in pul monary di seases causi ng right ventricular overl oad (e.g pul monary embol us)

Figure No Caption Available.

Key paper

Antman E et al Myocardi al infarcti on redefi ned—a consensus document of The Joi nt European Society of

Cardiology/American Coll ege of Cardi ology committee for the redefinition of myocardial i nfarction J Am Coll Cardi ol

2000; 36:959–69

McCull ough PA, et al B-type natriuretic peptide and cli nical judgment in emergency di agnosi s of heart fail ure:

analysis from Breathing Not Properl y (BNP) Multi national Study Circul ati on 2002; 106:416–22

See also: