Objective
The impact of obesity on maternal blood volume in pregnancy has not been reported. We compared the blood volumes of obese and normal-weight gravidas using a validated hydroxyethyl starch (HES) dilution technique for blood volume estimation.
Study Design
Blood volumes were estimated in 30 normal-weight (pregravid body mass index [BMI] <25 kg/m 2 ) and 30 obese (pregravid BMI >35 kg/m 2 ) gravidas >34 weeks’ gestation using a modified HES dilution technique. Blood samples obtained before and 10 minutes after HES injection were analyzed for plasma glucose concentrations after acid hydrolysis of HES. Blood volume was calculated from the difference between glucose concentrations measured in hydrolyzed plasma.
Results
Obese gravidas had higher pregravid and visit BMI (mean [SD]): pregravid (41 [4] vs 22 [2] kg/m 2 , P = .001); visit (42 [4] vs 27 [2] kg/m 2 , P = .001), but lower weight gain (5 [7] vs 12 [4] kg, P = .001) than normal-weight women. Obese gravidas had similar estimated total blood volume to normal-weight women (8103 ± 2452 vs 6944 ± 2830 mL, P = .1), but lower blood volume per kilogram weight (73 ± 22 vs 95 ± 30 mL/kg, P = .007).
Conclusion
Obese gravidas have similar circulating blood volume, but lower blood volume per kilogram body weight, than normal-weight gravidas near term.
Blood volume expansion in pregnancy is believed to be important for supporting normal obstetric outcomes. Obese individuals, despite having increased total blood volume, are known to have lower unit blood volume than lean individuals because fat mass is underperfused when compared to lean body mass. The prevalence of obesity among pregnant women continues to rise. The impact of obesity on circulating blood volume in pregnancy has not been well studied. In lean women, unit blood volume is 65 mL/kg in the nonpregnant state and increases to a mean of 100 mL/kg (range, 90–200 mL/kg) near term pregnancy. Unit blood volume has been shown to decrease asymptotically with increasing body mass, to a nadir of 45 mL/kg in nonpregnant class III obese women. A decrease in unit blood volume could contribute to the increased frequency of obstetric complications in obese gravidas including anesthesia-related adverse events.
Hypotension is a common complication of obstetric regional anesthesia placement and can result in category 2 and 3 fetal heart rate tracings and emergent delivery. Regional anesthesia induces sympathetic blockade, leading to decreased venous return that is mediated by blood volume. The resulting hypotension is commonly treated with additional intravenous volume and vasopressor administration. Prophylactic intravenous volume and/or vasopressor administration is commonly used prior to regional anesthesia to minimize the occurrence of hypotension. In our previously published studies, we have observed that class III obese women (body mass index [BMI] ≥40 kg/m 2 ) undergoing regional anesthesia for childbirth have more anesthesia-related hypotension and fetal heart rate abnormalities than lean gravidas. These factors may contribute to the increased cesarean delivery rate and associated perioperative morbidity among class III obese women, such as hemorrhage, endometritis, wound infection, venous thromboembolism, and respiratory depression.
We hypothesize that the obese gravida requires a larger volume infusion prior to sympathetic blockade and resulting peripheral venodilation than the normal-weight gravida. Fluid volumes that are sufficient to expand intravascular volumes and avert hypotension in normal-weight women may be inadequate to prevent hypotension in obese women who have greater circulatory volume capacity. A better understanding of the blood volume of obese gravidas at term may contribute to alterations in intrapartum hemodynamic management. We sought to compare the total and relative blood volume of obese and lean gravidas near term using a dilution technique based on the colloid volume expander, hydroxyethyl starch (HES). We also sought to compare these calculations to blood volume estimates based on weight alone.
Materials and Methods
This study was performed in the Clinical Research Unit of the Case Western Reserve University Clinical Translational Research Collaborative (UL1 RR024989) at MetroHealth Medical Center, with institutional review board approval, and with written consent of each participant. All studies were performed on otherwise healthy women who were at least 18 years of age and at least 34 weeks’ gestation. Women were recruited into 2 groups: lean (pregravid BMI <25 kg/m 2 ) and obese (pregravid BMI >35 kg/m 2 ). Women with preeclampsia, chronic hypertension requiring medication, insulin-dependent diabetes mellitus, renal or autoimmune diseases, bleeding disorders, congestive heart failure, and known allergy to corn or HES were excluded.
HES method
The HES method has been found to be highly accurate and precise and has been validated against the carbon-monoxide method in anesthetized neurosurgical patients in the intensive care unit. HES is used clinically for plasma volume expansion in obstetric patients, and has been administered in various clinical trials for this purpose in the obstetric and anesthesia literature. The HES method for blood volume estimation is a rapid, safe, and acceptable technique for use in pregnant patients, and does not cross the placenta.
Proposed by Tschaikowsky et al in 1997, the HES method uses HES as a dilution marker and calculates blood volume from the difference of glucose concentration obtained by acid hydrolysis of plasma before and after injection of HES. Blood samples are collected before and after intravenous injection of HES. Derived plasma samples then undergo acid hydrolysis to disrupt the alpha glycosidic bonds and produce constant proportions of glucose and hydroxyethyl glucose. Comparison of hydroxyethyl glucose concentrations in the 2 samples yields a reproducible calculated total blood volume.
Baseline measurements
Height, weight, blood pressure, pulse, and fetal heart tones were obtained on arrival at the medical center and used to calculate BMI and body surface area. Pregravid weights were obtained from direct measurements in the 3 months prior to pregnancy or at the first prenatal visit if <10 weeks’ gestation. Urine-specific gravity and serum creatinine were measured to gauge hydration status.
Sample collection
Patients were placed in the left lateral recumbent position for 30 minutes. An 18-gauge antecubital intravenous catheter was placed. Hespan (6% hetastarch in 0.9% sodium chloride) (DuPont, Wilmington, DE), 170 mL, was injected intravenously over 4 minutes followed by a 1-mL saline flush. Whole blood was collected in EDTA tubes prior to and then 10 minutes after HES injection, from opposite arms. The timing of the second blood draw was determined by a preliminary mixing study in which HES concentration was measured at 5-minute intervals from 0-60 minutes after HES injection in 10 volunteers (5 lean and 5 obese), with steady state observed at 10 minutes postinjection for both groups. Body composition measurements were performed using air displacement plethysmography (BOD POD; COSMED, Rome, Italy) to estimate the subject’s percent lean and fat mass.
Hematocrit was determined using a microhematocrit centrifuge. Plasma was separated from whole blood by centrifugation. Plasma (0.6 mL) was transferred into steam-tight tubes containing 0.15 mL concentrated hydrochloric acid (12 mol/L) and hydrolyzed in boiling water for 7 minutes. 0.65 mL of 3.33 mol/L Tris buffer was then added and incubated at room temperature for 6 minutes to bring the pH to 7.0 ± 0.5. The supernatant was recovered by centrifugation (3600 rpm, 16 minutes). Glucose in the supernatant was measured using the HemoCue 201 Glucose Photometer (HemoCue; Biotest, Frankfurt, Germany).
HES blood volume calculation
Blood volume was calculated using the equation: blood volume [mL] = k [HES volume (mL)] 3082 mg%/Δglucose/(1-hematocrit). HESV equals the volume of HES injected (mL). Δglucose (mg%) is the difference of glucose concentration, after hydrolysis in plasma. The constant, k (3082 [mg%]), is the slope of the linear regression line obtained by plotting Δglucose against the HESV/plasma volume ratio for varying in vitro dilutions of HES in whole blood.
Weight-based blood volume calculation
Weight-based estimate of blood volume was determined using the equation developed by Feldschuh and Enson. It uses sex, height, weight, and deviation from desired weight to calculate blood volume as follows: blood volume (mL) = [blood volume to body weight ratio (mL/kg)] [body weight (kg)] = 45.2 + 25.3 exp(–0.0198 × DDW). DDW is deviation from desirable weight (%) = 100 [body weight (kg) – DW (kg)]/[DW(kg)]. DW is desirable weight (kg) for women = 7.090 exp[0.01309 * (body height [cm]).
Statistics and sample size estimate
We note that the unit blood volume for normal-weight gravidas near term is 100 mL/kg. To detect a 30% decrease in unit blood volume in obese gravidas, at an alpha of 0.05 and a beta of 0.1, 30 women would be needed in each group, giving a sample size of 60 patients. We compared patient characteristics and blood volume estimation techniques between lean and obese gravidas using t tests for paired and independent samples and Mann-Whitney U test for nonnormally distributed data. We performed simple linear regressions to compare HES blood volume estimates using BMI and body composition as measured by air displacement plethysmography. Statistical analyses were performed using commercially available software (SPSS, version 18.0; IBM Corp, Armonk, NY).
Results
A total of 60 gravidas at ≥34 weeks’ gestational age enrolled in the study. Thirty women had pregravid BMI of ≤25 kg/m 2 and 30 women had pregravid BMI of ≥35 kg/m 2 . The data from 1 patient were excluded due to sample processing errors, leaving 29 lean and 30 obese patients. The mean pregravid and gravid BMIs were 22 ± 2 and 27 ± 2 kg/m 2 for the normal-weight patients and 41 ± 4 and 42 ± 4 kg/m 2 for the obese patients ( P < .001 for both) ( Table 1 ). The lean women gained more weight during pregnancy than the obese women (12 ± 4 vs 5 ± 7 kg, P < .001). Mean body composition, as determined by the BOD POD was: 72 ± 5% lean and 28 ± 5% fat mass in the lean group, compared with 57 ± 5% lean and 43 ± 5% fat mass in the obese group ( P < .001) ( Table 1 ). A patient experienced a hypersensitivity reaction consisting of a rash and urticaria after HES injection, and was treated with oral antihistamines without further complications.
| Characteristic | Lean | Obese | P value |
|---|---|---|---|
| n | 29 | 30 | |
| Weight | |||
| Pregravid BMI, kg/m 2 | 22 ± 2 | 41 ± 4 | .001 |
| Study visit BMI, kg/m 2 | 27 ± 2 | 42 ± 4 | .001 |
| Weight gain, kg | 12 ± 4 | 5 ± 7 | .001 |
| Body composition | |||
| Percent lean, % | 72 ± 5 | 57 ± 5 | .001 |
| Percent fat, % | 28 ± 5 | 43 ± 5 |
Blood volume comparisons
For the total cohort, the HES method produced a higher mean blood volume estimate than the weight-based formula, 7500 ± 2600 vs 5000 ± 500 mL ( P = .001). For both lean and obese women, the blood volume estimates by the HES method were higher than for the Feldschuh and Enson equation based on sex, height, weight, and deviation from desired weight ( Table 2 ). Although total blood volumes calculated by the HES method were similar between obese and lean women (8103 ± 2452 vs 6944 ± 2830 mL, P = .1), obese women had lower blood volume per kilogram when compared with normal-weight women (73 ± 22 vs 95 ± 30 mL/kg, P = .007).
| Variable | Lean | Obese | P value |
|---|---|---|---|
| n | 29 | 30 | |
| Blood volume, mL | |||
| BV-HES | 6944 ± 2830 | 8103 ± 2452 | .1 |
| BV-FE | 4417 ± 436 | 5568 ± 602 | < .001 |
| Blood volume, mL/kg | |||
| BV-HES | 95 ± 30 | 73 ± 22 | .007 |
| BV-FE | 63 ± 4 | 50 ± 2 | < .001 |
Comparison of BMI and blood volume calculated by the HES method revealed that the blood volume per kilogram decreased as BMI increased (y = –1.372x + 130, adjusted r 2 of 0.2) ( Figure 1 ). Evaluation of blood volume calculated relative to percent lean body mass, as measured by air displacement plethysmography, revealed a weakly positive correlation (y = 0.91x + 25, adjusted r 2 of 0.1) ( Figure 2 ).
