EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS 2008, Vol. 33, No.1, pp. 53-59

Influence of pregnancy on one-compartmentalbio-metric blood loss calculations after cesarean sectionand gynaecological surgery

JOVAN POPOVIC l and ZORICA GRUJIC2

'Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, Novi Sad,Republic of Serbia; 2Department of Gynecology and Obstetrics, Faculty of Medicine, University Hospital ofNovi Sad, Novi Sad, Republic of Serbia

Receivedfor publication: November 1,2007

Key words: Blood loss, calculations, haemoglobin levels, cesarean section

SUMMARY

To date there are no data in the literature on the procedure for the indirect measurement of blood loss during cesarean section, based onthe post-operative drop in haemoglobin (Hb), which has been due to the lack of biometric ally determined parameters for the calculationof blood volume in pregnant women. This study was therefore conducted to determine the applicability of the drop in Hb levels bloodloss calculation during cesarean section, based on a model previously validated in non-pregnant women. We compared this procedurein 54 patients who underwent cesarean section and 12 non-pregnant patients subjected to gynaecological surgery. The coefficient of theregression slope for the blood volume collected during surgery and the calculated blood loss in pregnant (y=0.6286x+366) andnon-pregnant patients (y=0.7605x+514) did not show any significant difference (t=1.I009, p>0.5, 95% confidence interval:-2.736,+2.473). Our study therefore demonstrated the applicability of the procedure for the indirect measurement of surgical blood loss both inpregnant and non-pregnant women.

INTRODUCTION

There are two ways of measuring blood loss: one is bythe direct measurement of collected blood (swabs,bottles with a suction device, drainage bags, etc.), andthe other is by indirect measurement. The latter re­flects blood loss through the assessment ofhaemoglobin (Hb) concentrations, haematocrit (Hct),the patient's blood volume, or the need for bloodtransfusions (1-3).

The amount of blood collected via swabs is oftenestimated by visual assessment. However, this ap­proach has poor reliability and validity. Weighing the

'Please send reprint requests to: Prof. Dr. Jovan Popovic,Department of Pharmacology, Toxicology and ClinicalPharmacology, Faculty of Medicine, Hajduk Veljkova 3,21000Novi Sad, Republic of Serbia.

swabs is an improvement upon this, but there is al­ways some evaporation and dilution. The swabs maybe dry or partially wet before use and may also haveabsorbed irrigation fluids, exudate or, in the case ofcesarean section, amniotic fluid. Swabs can be washedto extract the blood, but this is a complicated proce­dure.

The volume or weight of blood from bottles with asuction device can be used to assess blood loss. Thismay also be inaccurate, as often only small volumesare collected. Blood may remain in the tubes con­nected to the suction bottles and there is the furtherproblem of dilution (again irrigation fluids, exudatesand amniotic fluid), which may influence the accuracyof the estimation.

The drainage of blood from the operative site maybe incomplete for different reasons. Blood may remainin the operative area, where only some compartments

54 Eur. 1. Drug Metabol. Pharmacokinet. 2008, No 1

are drained. Moreover, clotting may occure in thedrainage tubes. Large volumes may remain in theoperative site with no external evidence of this beingthe case. The function of the drainage system may alsodepend on the type of treatment, e.g. if haemostaticdrugs are being investigated, drainage may be im­proved with one treatment than with another.

Direct measurement of blood loss does not take intoaccount the possible presence of haematomas or hae­molysis, which are significant causes of blood loss andwhich should be considered as being of the sameimportance as overt blood loss.

A drop in Hb levels is the usual means of indirectlymeasuring blood loss (2,3), and is an accurate method(2,3). The presence of haematomas and haemolysis isimplicitly taken into account. The second indirectmeasurement of blood loss is transfusion volume,which has a direct clinical relevance. However, thetransfusion policy in question, compliance with thetransfusion policy and the use of different bloodpreparations may vary from centre to centre.

To date there are no data in the literature on theprocedure for the indirect measurement of surgicalblood loss in pregnant women and during cesareansection based on pre- and post-operative Hbconcentrations. This is due to the lack of biometricallydetermined parameters for blood volume determina­tion in pregnant women. Our study was thereforeconducted to determine the applicability of the drop inHb levels in blood loss calculation (1,3) during cesar­ean section, based on a model that had previously beenvalidated in non-pregnant women (4,5).

MATERIALS AND METHODS

Study design

This clinical trial was open, controlled, prospective,random and comparative in design.

Study procedures

The clinical part of this study took place betweenApril 2003 and April 2005 at the Department ofGynecology and Obstetrics, Medical Faculty, Univer­sity Hospital of Novi Sad, Autonomous Province ofVojvodina, Republic of Serbia. The study protocolwas reviewed and approved by the InstitutionalScientific and Ethics Committee, and was performedin accordance with the ethical standards laid down inthe declaration of Helsinki. All patients participatingin the study were enrolled following their informedconsent.

Patient population

The patients included in the study were aged between19-40 years, and either scheduled to undergo cesareansection (54 women) or gynaecological surgery (12women) under general anaesthesia. The groups weredemographically similar.

Selection criteria for pregnant women

This study included pregnant women with a knowndate of the last menstrual period, regular menstrualcycles preceding pregnancy, with no previous familyor personal medical case history, who had undergoneregular control examinations during pregnancy, with anormal clinical course of pregnancy and normallaboratory findings, with date of completion of preg­nancy and gestational stage confirmed byultrasonography in early pregnancy.

This study did not involve patients who were vitallyendangered (preeclampsia and eclampsia), withlife-threatening health conditions for the foetus, orthese with a previous history of diabetes, hypertensionand other disorders (cardiovascular, neurological,metabolical, immunological, infectious or oncologicaldiseases).

Selection criteria for non-pregnant women

The investigation included 12 non-pregnant patientswho were scheduled to undergo gynaecological sur­gery.

Inclusion criteria were as follows: patients who werescheduled for gynaecological surgery, who had beenpreviously examined, patients with regular laboratoryfindings, those who had been recommended forsurgical treatment with the anaesthesiologists andinterns consent, subjects with regular vaginal secre­tions and Pap test results, patients subjected to otherdiagnostic examinations if necessary.

The criterion for non-inclusion of patients was asfollows: vitally endangered patients, who could notobtain the anaesthesiologists and interns consent forsurgical treatment.

Data collection

The following data were collected, recorded, and (or)calculated in electronic form: age, body weight, height,duration of surgery, blood transfusion and other fluidvolumes administered, Hb concentrations, Hct (beforeand after surgery) and estimated intraoperative bloodloss.

J. Popovic, et al., Blood loss calculations after cesarean section and gynaecological surgery 55

Determination of blood loss

Blood loss was collected directly in the swabs and by asuction device.

The drop in Hb levels is the usual means of indi­rectly measuring blood loss, although Hct may also beused instead. Either method can be chosen, becausethere is an almost constant relationship between Hband Hct:

Hct(%) = Hb(gL·1)/3.4

If a patient has a preoperative blood volume BV anda peri-operative blood loss V, then the Hb levels willfall according to a one-compartmental kinetic model:

·(VIBV)Hbpostop = Hbpreop.e .

Therefore if Hb (gL-1) and (or) Hct (%) has beenmeasured before and after the operation, as was thecase in our study, the blood loss may be calculatedusing the equation of Flordal (3):

V = BV· In(HbpreoplHbpstop)

The patient's preoperative blood volume was calcu­lated using the equation of Allen et al. (4):

BV = 0.414 H3 + 0.0328 BW - 0.030 (L),

as optimized by Nadler et al. (5):

BV = 0.3561 H3 + 0.03308 BW + 0.1833 (L),

where H = height (m) and BW = body weight (kg).During the operative period, the patients received

500 mL of physiological fluid by infusion and500-1000 mL immediately after surgery. Variations inblood volume and fluid balance could affect the bloodloss calculations, but computer simulations haveshown this to be of minor importance (3,6,7).

Statistical analysis

Comparisons were made by using the Student's t-testfor continuous variables. The statistical calculationswere performed mainly using the SAS StatisticalSoftware package for personal computers, release 6.12for Windows (SAS Inc., Cary, NC, USA). Atwo-tailed p-value was used with the level of statisti­cal significance being p <0.05.

RESULTS

The demographic, operative and laboratory data, di­rectly measured and indirectly calculated blood lossfor women who underwent cesarean section and

non-pregnant women who underwent gynaecologicalsurgery are shown in Tables I and II. Significantstatistical differences were found between the calcu­lated preoperative blood volumes (Tables I and II) inpregnant (4.51±O.5 L) and non-pregnant (4.05±O.34L) women (t=3.026, p«O.Ol). Preoperative bloodvolumes in pregnant women were calculated accord­ing to the same formula as that determined fornon-pregnant women by Allen et al. (4) and Nadler etal. (5). The comparison between directly measured(416 ± 231 mL) and indirectly calculated (627 ± 392mL) blood loss in women who underwent cesareansection (Table I) as assesed by the Student's t-test (fordependent variables) showed a significant difference(t=4.144, p<O.Ol). The comparison between directlymeasured (196 ± 92 mL) and indirectly calculated(663 ± 449 mL) blood loss in non-pregnant womenwho underwent gynaecological surgery (Table II) asassesed by the Student's r-test (for dependent vari­ables) also showed a significant difference (t = 3.639,p<O.Ol). The comparison between directly measuredblood loss in women who underwent cesarean section(416 ± 231 mL) and non-pregnant (196 ± 92mL)women who underwent gynaecological surgery (Ta­bles I and II) as assesed by the Student's t-test showeda significant difference (t=5.347, p<0.05). However,the comparison between indirectly (exactly) measuredblood loss in the case of cesarean section (627 ± 392mL) and that for non-pregnant (663 ± 449 mL) womenwho underwent gynaecological surgery (Tables I andII) as assesed by the Student's t-test showed nosignificant difference (t=O.279, p>0.5).

In the 54 women who underwent cesarean section(Fig. 1), there was a significant correlation betweencollected blood volume (x) and calculated blood loss(y=0.6286x+366, r=0.3707), since the correlationcoefficient (r) differed significantly from zero(t= r,}N-2 / ~1_r2 = 2.878, p<O.Ol). No suchcorrelation was found in the 12 non-pregnantgynaecological patients (y=0.7605x+514, r=0.1550,t=0.4961 , p>0.5), as shown in Figure 2. But theregression lines for the two methods, i.e. direct andindirec assessment in pregnant (y=0.6286x+366) andnon-pregnant women (y=0.7605x+514) were parallel(Fig. 3). No significant statistical difference existedbetween the slopes of the two regression lines. TheStudent's t-test used for calculating the regressionslopes was as follows:

t = (0.7605-0.6286)/s(0.7605-0.6286) = 0.1009, p> 0.5,

where:

56 Eur. 1. Drug Metabol. Pharmacokinet. 2008,No 1

1 1 _~ "2 n2 "2S(O.760S·0.6286)= Szd' nl _ 2 + n2 _ 2 Szd - 2... (Y1i - Y1i) + L(Y2j - Y2j)

L(X1i - Xd .L(X2j - X2 ) i=l j=li=l J=l (n1 - 2) + (n2 - 2)

X = blood loss estimated by the direct method in n, pregnant (Xli) and n2 non-pregnant women (X2j); Y = blood loss estimated by theindirect method in n1 pregnant (Y Ii) and n2non-pregnant women (Y2j), n1 =54,n2=12;Y=values of Y estimated by the regression linefrom the values of X.

Table I. Demographic, operative and laboratory data, directly measured and indirectly calculated blood loss in women who underwentcesarean section.

Patient Weight Height Duration of Collected Blood Preoperative Preoperative Postoperative Postoperative CalculatedNo (kg) (ern) surgery blood volume haemoglobin haematocrit haemoglobin haematocrit Blood loss

(min) (mL) (L) (gL· 1) (%) (gL-1

) (%) (mL)

1 70 159 30 300 3.93 103 31.1 99 30.3 1562 90 168 30 300 4.85 124 37.3 110 31.0 5813 85 174 30 400 4.87 110 30.5 80 26.2 15514 66 168 50 200 4.06 120 36.5 95 28.2 12915 72 170 45 500 4.31 134 38.0 105 30.9 10526 97 166 50 500 5.02 115 35.0 89 27.2 12877 87 170 40 300 4.81 119 35.4 102 30.0 7428 90 185 40 1200 5.42 102 29.9 80 27.0 13169 87 165 45 400 4.66 119 34.6 104 31.1 62810 93 157 50 400 4.64 99 29.2 89 26.7 49411 65 170 45 400 4.08 101 29.8 95 24.5 25012 96 173 45 250 5.20 128 37.5 104 31.3 108013 90 165 45 200 4.76 113 33.5 108 32.3 21514 123 164 70 300 5.82 113 34.2 105 31.2 42815 85 170 50 500 4.74 129 37.0 114 32.6 58616 70 168 35 300 4.19 126 36.7 120 35.2 20417 75 175 55 300 4.57 105 31.9 98 29.7 31518 90 169 40 100 4.88 112 33.0 106 32.3 26919 82 162 45 450 4.41 120 37.0 106 33.0 547

20 90 170 35 500 4.91 109 34.0 99 31.0 47221 66 169 25 300 4.08 130 40.0 126 39.0 12822 55 152 50 300 3.25 99 31.0 88 24.0 38323 75 171 40 300 4.44 128 39.8 110 37.0 67424 95 177 30 200 5.30 120 35.2 100 33.0 96625 80 170 35 350 4.58 109 35.2 102 31.9 30426 65 160 55 200 3.79 103 30.5 93 30.0 38727 85 180 50 500 5.07 98 29.3 82 25.1 90428 80 170 60 200 4.58 128 38.3 108 32.6 77829 72 157 45 250 3.94 125 38.5 110 35.5 50430 70 156 40 800 3.85 112 36.2 99 29.2 47531 73 161 40 600 4.08 121 36.5 91 27.5 116432 77 161 40 200 4.22 118 35.5 114 34.0 14533 69 179 40 400 4.51 109 32.6 104 31.0 21234 75 165 30 100 4.26 108 31.7 107 31.5 4035 69 163 30 150 4.01 120 36.6 113 33.1 24136 62 163 30 400 3.78 114 31.8 89 26.6 935

J. Popovic, et al., Blood loss calculations after cesarean section and gynaecological surgery 57

37 70 166 65 500 4.13 118 35.0 82 23.9 150238 71 165 40 300 4.13 106 31.7 102 30.3 15939 68 165 55 800 4.03 131 37.3 111 32.5 668.40 77 166 40 900 4.36 100 29.0 90 26.5 45941 79 160 55 400 4.25 105 31.6 102 29.6 12342 80 170 55 1000 4.58 105 30.2 83 24.1 107743 83 173 40 400 4.77 110 32.1 87 25.8 112244 85 160 45 1000 4.45 101 30.9 84 25.6 82145 64 160 45 350 3.75 125 36.7 105 33.7 65546 80 177 50 250 4.80 132 37.9 120 35.0 45847 91 172 40 700 5.01 130 37.9 114 33.8 65748 85 175 45 500 4.90 118 34.7 108 32.0 43449 84 170 35 450 4.71 112 35.0 107 32.0 21550 95 167 50 300 4.98 99 30.2 82 25.3 93951 77 168 40 500 4.42 98 28.6 82 25.5 78852 70 158 40 300 3.90 109 32.9 100 31.0 33653 101 168 40 500 5.21 147 42.8 117 33.8 119054 95 174 25 250 5.20 110 32.0 99 29.3 548

X 80 167 43 416 4.51 115 34.2 100 30.2 627

±SD 12 7 10 231 0.50 11 3.3 11 3.5 392

1500 :::J • •1400 ..s

(j)

1300(j) •0 • •...J

1200 00 •0 •

1100 ...J •IX) •0 •

1000· Wt{ • • •900 ...J •::>o •800 ...J« • •U •

700• • •

600 •500 • •• •• •400 • • y = O.6286x + 366

•300 • • r=O.3707

• • • t=2.878200 • • • • p<O.01

• -:100 • N=54

•0 100 200 300 400 500 600 700 800 900 10001100 1200

COLLECTED BLOOD (mL)

Figure 1. Regression curve y =0.6286x + 366 with a high correlation coefficient (r) between the collected blood volume (x) andcalculated blood loss (y) in 54 women who underwent cesarean section, with the existence of a significant difference of r from zero: t =rJN-2 /~1_r2

58 Eur. J. Drug Metabol. Pharmacokinet. 2008, No I

Table II. Demographic, operative and laboratory data, directly measured and indirectly calculated blood loss in non-pregnant womenwho underwent gynaecological surgery.

Patient Weight Height Duration Collected Blood Preoperative Preoperative Postoperative Postoperative CalculatedNo (kg) (em) of surgery blood volume haemoglobin haematocrit haemoglobin haematocrit Blood loss

(min) (mL) (L) (gL-1) (%) (gL-1) (%) (mL)

1 65 172 52 100 4.15 133 40.0 100 29.8 1182

2 60 168 30 100 3.86 142 42.0 128 38.4 400

3 59 165 40 50 3.73 132 38.8 121 37.0 325

4 75 170 75 300 4.05 119 34.0 80 25.2 1609

5 73 174 45 200 4.47 103 31.0 97 29.6 268

6 72 165 25 200 4.16 116 35.6 110 33.8 221

7 58 167 50 300 3.76 126 36.0 116 34.5 311

8 76 160 90 300 4.16 128 36.1 112 33.7 555

9 60 170 30 200 3.92 120 35.0 100 32.0 714

10 55 165 80 100 3.60 159 35.0 119 33.0 1044

11 60 171 45 200 3.95 130 36.0 120 34.0 316

12 90 167 120 300 4.82 127 37.0 103 29.9 1009

X 67 168 57 196 4.05 128 36.4 109 32.6 663

±SD 10 4 29 92 0.34 14 2.9 13 3.6 449

Figure 3. Parallel regression lines for the two methods inpregnant and non-pregnant women. No significant statisticaldifference existed between the slopes of the two regressionlines. The Student's t-test for regression slopes was as follows:t = (0.7605-0.6286)1 (0.7605-0.6286)/s(0.7605_0.6286) = 0.1009,p>0.5. The 95% confidence interval for the difference betweenthe slopes of the two regression lines: [-2.736, +2.473] containszero.

1600 •1500

1400

1300

1200 •1100

1000

z:S 900

(J) 800(J)

0..J 700000 600..JCD0 500--W

~ 400 •..JY = 0.7605x + 514:::> • • •o 300 r=0.1550..J •s 200 • t=0.4961p>0.5

100' - N=12

0 100 200 300 400 500 600 700 800

COllECTED BLOOD(ml)

1600

::; 1400

S~ 1200

s01000

9CD 800oW

~..J:::>U..J

()200

o

------ - -- ----- ---- -- ----- ---- ------------ - ---- -- ~ -- - - - --,,,

0.7605-0.6286t= ----- = 0.1009

S(0.7605-0.6286)

p>0.595% CI:[-2.736, +2.473]

200 400 600 800 1000 1200 1400 1600

COllECTED BLOOD(ml)

Figure 2. Regression curve y = 0.7605x+514 with a correlationcoefficient (r) between the collected blood volume (x) andcalculated blood loss (y) in 12 non-pregnant sectionedgynaecological patients, with no existence of significantdifference of r from zero: t= r"N- 2 Nl- r 2

DISCUSSION

As this aspect had not been previously considered,there was a need for a biometrical investigation into

J. Popovic, et al., Blood loss calculations after cesarean section and gynaecological surgery 59

the determination of new parameters for pregnantwomen in the blood volume formula determined fornon-pregnant women b1Allen et al. (4) and Nadler etal. (5): BV =0.3561 H + 0.03308 BW. The applica­tion of this formula, determined for non-pregnantwomen, to pregnant women, overestimates BV duringcesarean section because BW includes not only of thewomen but also of the fetus and of the amniotic fluid.But the influence of BW in the above-mentioned for­mula (0.03308 BW) is minimal in comparison with H(0.3561 H\ This together with the present findingssuggests that the established procedure for the indirectmeasurement of surgical blood loss in non-pregnantwomen can also be applied to pregnant women with asufficient degree of accuracy. Future investigationsmay improve the determination of BV and the indirectmeasurement of surgical blood loss in pregnantwomen. Therefore the present results are preliminaryin nature, and need to be confirmed by further studies.

CONCLUSION

Our results have demonstrated the applicability of theprocedure for the indirect measurement of surgicalblood loss, with similar accuracy, both to pregnant andnon-pregnant women, since the regression lines of thetwo methods were found to be almost identical, i.e.parallel.

ACKNOWLEDGEMENTSThe excellent technical assistance of Mrs Vesna Pop­ovic is gratefully acknowledged. This study was sup-

ported by Grant No. 114-451-00663-2005-01 from theSecretariat for Science and Technological Develop­ment of the Autonomous Province of Vojvodina, Re­public of Serbia. Declaration: The experiments wereconducted in compliance with the current legislationin Serbia and were performed following ethical ap­proval.

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