Pediat. Res. 11: 1171-1177 (1977) Effective pulmonary capillary blood flow neonate impedance cardiography nitrous oxide
Cardiac Output in the Neonatal Period Using Impedance Cardiography
KATE COSTl'LOL.'" '' JANLT STOCKS. ANDS. CiODFREY
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Summary childr<:n by comparison with invasive methods with encouraging results (I. 'J . 12. l-l- 16. 18. I')). This paper describes a study comparing the impedance cardiac To our knowledge. this method has not previously been us<:d output (ICO) with effective pulmonary capillary blood now in infants. This pap<:r describes a study comparing impedance (Qpc etT), measured by rebreathing N~O, in a group of healthy cardiac output (ICO) with Ope df. measured by rebreathing babies during the neonatal period. The calculation of ICO nitrnus ,ixide (N,O) . in a group of healthy babies during th<: requires a value for the electrical resistivity of blood, p. The neonatal period. resistivity of blood was measured on 40 samples of neonatal blood with hematocrit range of 18-70% and a new relationship was defined between haematocrit and resistivity·, whereby p = l\1ATERIALS AND METHODS 67.919 exp (0.02433 Hct) (Fig. 2). A total of 109 simultaneous measurements of Qpc eff and ICO, made from 32 different IMPFDAN(T CARDIO(iRAPHY occasions, was considered for correlaJion babies studied upon 41 Th<: instrum<:nt us<:d to measure the cardiac output in this (Table 2). The different methods are plotted against purposes study was a Minnesota impeuance L'aruiograph . moud 304A. (Fig. 3). It is seen that using any one each other in the graphs This utilizes four disposable aluminized Mylar strip electroues. for human_ blood resistivity alone, a good of the available data In the adult two of these are placeu around the neck. with th<: ICO and Qpc eff is only achieved over a correlation between third just bL·low the xiphisternum and the fourth at least 3 L'm correction part of the haematocrit range. A hematocrit-related distal to the third. A constant sinusoidal alll'rnating current of -l S, has been derived to be applied to the stroke volume factor, ma rms at I 00 kllz is passed longitudinallv betw<:c·n the outer ICO compared with Qpc eff results is equation. The corrected two del'trnd<:s. The prouuct of this curr<:nt and the transthoracic the correlation coefficients and percent shown in Figure 5 and impedancl' . Z., ohms . obeying Ohm's law. g<:neratcs a voltage between the two methods for the different age differences which varies with the cardiac cycle anu whi<:h is rernrueu groups are shown in Table 2. The mean ICO is 205 hematocrit between the two inner electrnues by a high input imp<:dance ml kg ' min ', SEM 3 .5 ( range 124-289). linear amplifier. In this stuuy. the outputs taken from the Impedance cardiography is a safe and easy technique to apply machine \\-ere: the mean transthoracic imp<:uance. Z 11 ohms. newborn human infant but even if accurate values for to the given in digital display hy the machin<:; the first u<:rivatiw of a further hematocrit-related factor should resistivity are used, the impedance cardiogram. uZ/dt ohm sec '; an ECG recorueu results. be applied for optimal between the outer two eleetrodes and a phono<:ardiogram. the latll'r two signals being used as timing uevices. Speculation It was impossible to put two ele<:troues around the short neck placed on A technique having been established hy which impedance llf a young babv . ThL· first electrode was therdor<: mean transth,>racic imp<:dance cardiography can he used to make accurate measurements of th<: hnl\\. It was found that th<: of cardiac output in the healthy newborn infant, it is now possible valu<:. Z., ohms. was more stable. anu that a b<:tter 4uality the to use this method to provide noninvasive observations on the recording was obtained if ekctrod<: jelly was appli<:u to on and the normal cardiovascular physiology of the newborn and to assess brow electrode. The apparatus was always switcheu was its potential for making clinically useful measurements on sick electrodes applied for at least I() min before a recoruing infants. L1kc· n . lmpeuancc cardiograms were obtain<:u while the chilli lay quietly. any muscular activity causing gross uistortion of the Th<: m<:thod which has h<:<:n most widdy us<:d for the 111H1in trace. ;\ tvpical satisfactory trace obtained is shown in Figure I. vasiv<: quantification of cardiac output in the n<:whorn human As the balw breathed. there was an inevitable swinl! of the infant is th<: m<:asur<:mcnt of the dkctivc pulmonarv capillarv baseline an;und the zero line anu in this studv care w:1s tak<:n hlond flow (Qpc df) by th<: rebreathing Df a solubl~ in<:rt ga~~ only to analyze heats which werl· mll uistorted l;y th<: respiratory (3. -l . 6. 10. 23 . 2-l) . This techniqul' is valid if thcr<: is normal swinl! . If this nill'rion was fulfilled . the bl·at was analvz<:d. th<: cardiovasn1lar and respirator\' functi,111. hut in a baby with height of dZ/ut min b<:ing m<:asur<:d from th<: comm<:n~emcnt of respiratory disease. wh,: n there is likdy to be an uneven the stl'ep upstroke. identified with the help of the FCG anu distribution of ventilation and perfusion or shunting of blliod. it phonocardiogram. irrl·sp<:ctive of the position of this point with cannot yidd reliable information. r<:spect to the baseline. This is in contrast to the usual method Impedance cardiography. which is alleged to measure L'ardiac of analyzing adult impedance· cardiograms which are less af output by 1.ktecting the transthoraeic impedanc<: changes asso kcteu by r<:spiratory swings and wh<:r<: the h<:ight. dZ/dt min. is L'iateu with the cardiac cyde . has he<:n assess<:d in adults and measured from thl· haselin<:. Car<: was taken to analvzc the 117 I 1172 COSTELOE rr AL.
previously described in Figure 2 and it can be seen that these I ECG I f'-.-~r- ~'____...,--~\_,.,..,--,----.,.._,.__ data give a higher value for the resistivity than any of the pre vious data. The· ICO's reported in this study arc denoted in four different ways. using four diffnent resistivity values abbreviated thus: dZldl /, \ ( IT:· I\ ICO ( K) = ICO calculated using resistivity data of Kubicek / 1 '1 ( 17); ICO (G&S) = ICO calculated using resistivity data of I 1 Geddes and Sadler ( 11 ); ICO (M&H) = JCO calculated using . dZ/dlmin I ' / \!Ohmsec- resistivity data of Mohapatra and Hill (21) from work with hlood of anemic dialysis patients; ICO (M.C&H) = ICO calculated using resistivity data i. .~ i of Mohapatra. Costcloc. and Hill (22) from 1) ~\ Ii \Yt work with placental and neonatal hlood samples.
MEASURl:MENT 01- Qp,· df Ll',':! _l __: __J The . cqimation of the effective pulmonary capillary blood . I I flow. Qpc cff. hy the rchrcathing of nitrous oxide. N,O. relics --,\.,.. __ -4-_-t---,. ,,, ,--- ... -- i-- ' Phonocardiogram upon the principle that the gas is absorbed into the· hlomlstrcam in proportion to the pulmonary blood flow and the concentration Fig. I. Typical impedance cardiogram from a quietly hreathing hahy. showing measurement of the value, dz/dt min and T. same numher of heats ahove and below the· baseline so that 320 variation of stroke volume during the respiratory cycle 11as Key allowed for. It was verv unusual for a trace to he so distorted hv 300 ...... (M,C&H) respiration that it could not he analvzcd and usuallv 8-1 2 heat·, ...... ( Kl were analyzed. · · 2111 t:r----6 (G&S) For each heat analvzcd the stroke volume . .l V. was calculated ( M&Hl from the equation · 290 .lV = jp(L/Z")' dZ/dt min·TJml (/) ---- where fJ is the rcsistivitv of human blood at 3 7° in ohm cm. L 2AO is the mean distance hct.wccn the two inner recording electrodes E in centimeters. Z 0 is the mean transthoracic impedance in ohms. u220 dZ/dt min is the maximum negative value of dZ/dt occurring E 1 during thc cardiac cyclc in ohms sec • and T is the ventricular 0200 ejection time in seconds. The values of dZ/dt min and T 11 ere >- ohtaincd from the tracing as shown in Figure I and the ICO !:: 1111 was calculated from the formula >
ICO = (mean .lV x HR) 1 ml min (2) ....ii, 110 1 where HR is the heart rate in heats min • a: 140
RLSISTIVITY OF BLOOD 120 The resistivity of hlood is related to the hcmatocrit. which was determined for each hahy from a hcelprick specimen of 100 hlood spun for 5 min on a Hawksley microhcmatocrit centrifuge. When this study was undertaken. four relationships he tween resistivity and the hcmatocrit of blood had hecn puhlished. 0 20 40 eo ., Those of Kubicek ( I 7) and of Geddes and Sadler ( I I) arc expo HAEMATOCRIT % nential and were derived from work with reconstituted time-ex Fig. 2. (iraph, shllwing ditfrn:nt relationships hetween pired hank hlood. The more recent relationships derived hy Hill hllllld resistiv ity and hematocrit. (M.C&H): neonatal and Thompson ( I 3) and Mohapatra and Hill ( 21) arc linear and hlood resistivity. Mohapatra, Cmtellle. and Hill (22); (K): Kuhicek resistivity 18); arc hascd on measurements made on frcsh samples of hlood data ( (G&S): Ciedde, and Sadlt:r resi,itivity daia ( 11 ); (M&H): drawn from adult patients from a renal dialysis unit with hema Mllhapatra and Hill ri:,istivitv 21). tocrits ranging from I ft-52,.,. data ( The electrical rcsistivitv ,if fresh samples of blood from fit human subjects has not previously hccn measured and this was Table I_. l?eprod11cihilirr of cffi•cfil'C' p11/111011ar_1· capillar_1· hlood performed as a part of the current investigation. During the jl
/ / /
•10,./ / / / Key ·1/0'l, / / . // Ke y / / 800 • • Hct > 35'1, 800 • • Hct > 35'!, / / / / / • • Hct~ 35'1, • • Hct.,; 35'1, ·0 ,. • / / •/-IQ'!, / / / •• 7 / 600 C 600 7 / E C :/ . E E • / E .. / •/' . . / ... • ;i· "' c:, / - 400 -~ .. 40 0 • :,r. . .. 0 /" 1/. 0 /. . . / / .. ,::/ / ...... 1/ • ' .. 200 / . 100 /
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/ / ,w,, / / / Key 800 • , :-;c t> "; )'; / / 800 o • Hct > 35'1- , He!< ~J·' • • Hct( 35'1, / / / .J o, ... / " C 7 / E • 600 • "r / . E 600 . c / r ·· /• ...... r u , / ... / "" . . / • oo /~ ,• . . - <1 00 0 0 . ;/ ;,· / , ,' ... . /": ... .. 1/ • /;!./ 200 . 100 /;1/ ) //
C D 200 400 600 100 200 400 ooo qoo QPC [FF ml m, n - I QPC EFF ,•1 1 ri ,n Fig. 3. Gra phs showing r.:latinnship bt:twl.'l.'11 c.:fkctivl.' pulmonary capillary hlnnJ flow ( {}pc cjj) anJ irnpcdanc<: cardiac output(/.( .0.) results with .!: I ll'i,, Jcviation. Thc four difkn:nt graphs rcprc.:sc.:nt four Jiffcrcnt cakulation, llf ICO using th<: Jifkrcnt Jata for hlllod rcsisitivity shown in Figure.: 2 . 11 7-i COSTELOE ET AL.
were made on Kodak Linagraph direct print photographic paper no selection 111 r~·spcct of gestational age. hirth weight. or using an ultraviolet light recorder. S .E. Lahs. S.E ..1006 . weight and age at the time of testing. anti none had clinical The hahy. swaddled in hlankets. with the impedance tape evidence of cardiovascular or respiratory ahnormality. Any electrodes already in place . was lain within the plethysmograph hahy in whom ldt to right shunting was indicated hy the
and the faccmask was gently lowered into pnsition, a seal hcing recirculation of N2 0 carrying hlood hcforc cquilihration had achieved hy means nf silicone putty (J . A. Carter Ltd .. Wilt hccn achieved was excluded from the study. The technique of shire). The lid of the plcthysmograph was secured and a volume. estimation of Ope cff hy rehreathing N, O has hcen used with equivalent to the estimated functional residual capacity of the healthy hahies hy other workers. The use of the impedance infant. of a mixture of ]() <'fr oxygen and 7() <7,-. nitrogen. was method caused no additional risk or discomfort and hoth meth injected into the hag. ods have hecn approved hy the Ethics Committee of this The hahy hreathed air from the plcthysmngraph until the hox hospital. pressure was stahlc. indicating that cquilihrium had heen RESULTS achieved with room conditions. With the hox closed. the taps were then switched so that he hreathed the oxygen/nitrogen A total of I 09 simultaneous measurements of Ope cff and mixture from the hag and the pump was started so that the !C O from 32 different infants studied upon 41 occasions were gases circulated. Rehreathing was continued for 30 sec. the hox considered for correlation purposes. The data for these infants pressure heing recorded. The fall in hox pressure while rehreath and ()pc eff and ICO determinations using the different resistiv ing 0 2/N 2 was caused hy the falling respiratory exchange ratio, ity values arc given in Tahlc 2 and the different methods arc ( = CO2 production/02 rnnsumption) and was used in the plotted against each other in the graphs ( Figure 3) showing the suhsequcnt calculation as the control slope. line of identity with :!:: I O'Jr. deviation . It is seen that , using the The 0 2/ N2 mixture was then replaced with a mixture contain Kuhicck ( 17) and the Geddes and Sadler ( 11) resistivit y data, ing 30% 0 2 and 70 'lr N20 . and the rchrcathing procedure was the impedance technique underestimates values in those infants repeated. The change in hox pressuro.: . the concentration of whose hematocrit was helow 35 r1, . N 2 0 sampled from within the face mask . and the impedance The Mohapatra and Hill (21) data produces a greater ten cardiogram were recorded simultaneously. Upon this occasion dency to underestimation. In contrast. using the Mohapatra, the change in hox pressure related to hoth the N20 uptake and Costeloc , a nd Hill (22) data from work with neonatal hlood the falling respiratory exchange ratio. samplcs. the correla tion is acceptahle in the anemic group hut It was found that equilihrium hetween the hag and the alveoli the ICO is overestimated in the Hct > JS % group. in terms nf nitrous oxide concentration was usually achieved Using the mean value for Ope cff each time an infant was within 8 sec of commencing rehreathing. and the period hctween studied as the standard. a correction factor, S, to he applied to IO and 20 sec was analyzed for Ope cff unless there was the !CO calculated using the accurate resistivity data. p[ICO evidence of recirculation of N,0-containing hlood hdore this (M,C&H)j (Fig. 2) , was derived , so that for each set of values. time. as indicated hy a sudden reduction in N20 uptake . in S = !Ope df)/(ICO (M .C&H)j . The values ohtained for S for which case the period of analysis was adjusted accordingly . each occasion an infant studied were then related to the relevant A factor to correct for the small leak in the plcthysmograph hematocrit value and nonlinear regression analvsis to find the was applied to hoth the control and test slopes, and the fall in line of hcst fit was performed (Fig. 4). hox pressure attrihutahle to N2 0 uptake alone was ohtained from the difference hetween the corrected slopes. This value was converted to volume hv application of the calihration factor. 1 2
Suhstituting the calculated rate of N20 uptake for VN2 0 in f' quation ., , tog<:thcr with the· ·,,due for F/\N,O ohtain..-d from the tracing. Ope eff was estimated. A more detailed account of the physical properties of the plethysmograph together with the ' 0 derivation of the equation to correct fo r pressure leakages is presented elsewhere (24) .
As the infant rehrcathed the N20 mixture . a simultaneous impedance cardiogram was performed and the ICO and Ope cff 0 • were calculated over precisely the same time period. Whenever possihle. three sets of simultaneous data were recorded from each hahv each time he was studied. In this· paper the results of hoth ICO and Ope eff measure 0 ments arc expressed in milliliters per min for the purposes z of 9 correlation and in milliliten, per kg per min for comparison with .... b:l the results of other workers. tr tr 0 u O 4 RE PRODlJCIBll.lTY
The reproducihility of hoth Ope cff and !CO was investigated S, 2 624. 11 21 log 10 H,_!¾ hv performing a paired I-test on the first two of each set of ohservations for each method and hy calculating the niefficie nt 1, 2 n , 41 , r , - 0 P7 5 5 . < 0 001 of variati11n of paired estimates (8) (C VPE) on the same data hy the formula, CVPE = (SDd/x) x Irnn, where SDd is the standard deviation of the difference hetween the pairs of ohser vations and x is the mean of all the ohscrva tions. The results of D--1----1>----1---t-~--+--+--+---- this analysis arc given in Tahle I which shows good reproduci 0 20 40 60 80 hility for hoth methods of measuring cardiac output.
H;, EM- TOCRIT ¾ SUBJECTS Fig. 4 . Ciraph showing the relationshp hl!lween the co m.:ction con The infants included in this study were all patients on the stant S. S = Ope c ff/ lCO (M ,C&H) (sec text) . and hema tocrit "+. with Premature Bahy Unit at the Hammersmith H11spital. There was the regression line . S = 2 .h 24 - I .12 t log ... He1 .
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I! • • :iuo11! :iuo11! ,\ llAllS!S:lJ llAllS!S:lJ L L ;)JI! ;)JI! pUl! pUl! . . ;,1q1:.1 ;,1q1:.1 UI UI llllln10.1 llllln10.1 ISi?( ISi?( ;,41 ;,41 ll! ll! ll,\\ll4S ll,\\ll4S l!ll!p l!ll!p :is;,4J , , ;)JI! ;)JI! ~o.:: ~o.:: . . :>,llll!J :>,llll!J llJ:l0ll!lU:l4 llJ:l0ll!lU:l4 0.)1 0.)1 p.-.J:l)Uno;m;, p.-.J:l)Uno;m;, ;,41 ;,41 JO JO 1rnd 1rnd s1 s1 1! 1! PAO PAO u1?:im u1?:im .IP .IP Ajllll Ajllll p;,A;,!4:11! p;,A;,!4:11! :141. :141. · · :imn1.:1 :imn1.:1 111 111 1n1!p 1n1!p :1<.Jq :1<.Jq ;,41 ;,41 01 01 p:i11?1;1J p:i11?1;1J JO JO s1u.-.ll1:lJllSl!:llll s1u.-.ll1:lJllSl!:llll '1)1 '1)1 :lAISl!Alll :lAISl!Alll :ll!l!lll :ll!l!lll 68Z-tZI 68Z-tZI -~·t 01 01 + + Jjql!l<.b:i:ll!un Jjql!l<.b:i:ll!un , , llllll llllll , , jlll jlll Aj(1!.1l4P Aj(1!.1l4P lt\l3S lt\l3S ', ', SI SI 11 11 :l Aead. Sci .. 170.· 747 (1'1711). transthoracic clcrtrical impedance. Biomed. En!( .. 7: 316 ( 1'172). ~. Y. . W . G .: U npuhlished data supplied with Minnesnta impedance 6 . Cotton. L K .. Co!(swell . J . J .. and C ropp. G . J. A .: Measurements of I 7 . Kuhieek cffcctivc pulml,nary hloo Prim<' d in U .S.A. Copyright ,c, 1977 International Pediatric Research Foundation. Inc . Pcdiat. Res. / / : 1177-1179 ( 1977) Acidosis human milk colostrum hyponatrcmia electrolytes pH Electrolyte and pH changes in Human Milk CHRISTINE ANSELL. AN(il'LA MOORE. AND H. UARRIE"';' Pa,•tliatric Re.H'arch Lahorawrr. Ch11ri11/i Cross Hmpiral. Lo11do11 , t:11!ila11t! Summary desirable modification both for premature infants and for term infants in the first few weeks of life. Milk samples from 100 lactating mothers in the 10 days following delivery have been analyzed for pH, sodium, and potassium. The sodium concentration was high in the first 5 Renewed attention has recently heen paid to thL' optimal days, mean 21 ± 5 mmol/liter, but fell to a mean 15 mmol/liter mineral composition of infant feeding formulas. lhe assumption bv the end of the first week and 12 mmol/liter by the 10th day. being that because human milk ii; physiologic it is less likely to A similar downward trend "'as shown for pot~ssium with ~n cause electrolyte or acid-base distrubances. The values usually initial mean concentration of 18.5 mmol/liter faJling to 15 quoted for sodium and potassium concentrations in breast milk. mmol/liter by the I 0th day. The pH fluctuated widely from day and to which artificial milk formulas aspire. refer to mature to day through a range of 6.75-7 .42 with a mean pH 7 .09. milk . all hough thl' different concenlrations in colostrum and Considerable variations were shown in individuals from day lo transitional milk have long becn rcc,lgnizcd (lJ). The aim of this day, and from the beginning lo the end of feeds (Table I). invcstigation was to dl'terminc thl' likely intakl' of sodium and The relatively high sodium concentration in the firsi few days potassium in the first IO days of life and to estahlish the normal may be an important defense mechanism against dehydration rangc of pH of colostrum and transitional milk. and hyponatremia during a period of relative thirst and starva tion. The variation in the pH and electrolyte content of human MATE RIALS AND METHODS milk may be expected to have some influence on the acid-base samples were laken wilh informed consent from a and electrolyte status of the infant. Milk random seril's of I()() lactating mothers. Milk was also collectcd from one paticnt for lhe IO consecutive days after delivery. • Speculation Specimens were collectl'd during the 9 AM feed hy hand Hyponatremia and acidosis in neonates in the first few weeks exprL'Ssion by thc mother assistcd hy one of us (C. Ansell) cleaned with may be attributed in part to the inappropriate pH and elertrolyte using a standard lechnique (2). The breast was content of artificial milk formulas based on mature human water only and :'i-ml samples were taken into sterik universal and at milk. The addition of sodium and base to formulas may be a containers approximatcly 1-2 min after starting the fecd