Review Article| Volume 50, 103274, May 2022

Download started.


The venous system during pregnancy. Part 2: clinical implications

  • L.C. Tsen
    Correspondence to: Harvard Medical School, Brigham and Women’s Hospital, Department of Anesthesiology, Perioperative and Pain Medicine, 75 Francis St, Boston, MA 02115, USA.
    Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
    Search for articles by this author
  • S. Gelman
    Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
    Search for articles by this author
Published:February 26, 2022DOI:


      • Pregnancy and co-morbid gestational states alter venous anatomy and physiology.
      • The venous system controls and responds to maternal hemodynamic states.
      • Dynamic interactions exist between venous unstressed (Vu) and stressed (Vs) volumes.
      • Hypotension often results from aortocaval compression or neuraxial technique use.
      • Hypertension is a heterogeneous group of disorders affecting venous function.


      Maternal positioning, medications, and other modulations to the venous system can affect maternal and fetal well-being. The venous system is a dynamic reservoir for blood volume, in which a virtual point of conversion between unstressed volume (Vu) and stressed volume (Vs) exists. The anatomic and physiologic changes associated with hypotension (e.g. supine and neuraxial technique-induced), hypertension (e.g. preeclampsia), and fluid management (e.g. early recovery after cesarean delivery protocols) are opportunities to consider the important role of the venous system in pregnancy.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to International Journal of Obstetric Anesthesia
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Higuchi H.
        • Takagi S.
        • Zhang K.
        • Furui I.
        • Ozaki M.
        Effect of lateral tilt angle on the volume of the abdominal aorta and inferior vena cava in pregnant and nonpregnant women determined by magnetic resonance imaging.
        Anesthesiology. 2015; 122: 286-293
        • Lee A.J.
        • Landau R.
        Aortocaval compression syndrome: time to revisit certain dogmas.
        Anesth Analg. 2017; 125: 1975-1985
        • Hogan Q.H.
        • Stekiel T.A.
        • Stadnicka A.
        • Bosnjak Z.J.
        • Kampine J.P.
        Region of epidural blockade determines sympathetic and mesenteric capacitance effects in rabbits.
        Anesthesiology. 1995; 83: 604-610
        • Mueller R.P.
        • Lynn R.B.
        • Sancetta S.M.
        • Heckman C.
        • Janouskovec H.
        Studies of hemodynamic changes in humans following induction of low and high spinal anesthesia. II. The changes in splanchnic blood flow, oxygen extraction and consumption, and splanchnic vascular resistance in humans not undergoing surgery.
        Circulation. 1952; 6: 894-901
        • Gelman S.
        Venous function and central venous pressure: a physiologic story.
        Anesthesiology. 2008; 108: 735-748
        • Sharwood-Smith G.
        • Drummond G.B.
        Hypotension in obstetric spinal anaesthesia: a lesson from pre-eclampsia.
        Br J Anaesth. 2009; 102: 291-294
        • Baumann H.
        • Alon E.
        • Atanassoff P.
        • Pasch T.
        • Huch A.
        • Huch R.
        Effect of epidural anesthesia for cesarean delivery on maternal femoral arterial and venous, uteroplacental, and umbilical blood flow velocities and waveforms.
        Obstet Gynecol. 1990; 75: 194-198
        • Tawfik M.M.
        • Tarbay A.I.
        • Elaidy A.M.
        • Awad K.A.
        • Ezz H.M.
        • Tolba M.A.
        Combined colloid preload and crystalloid coload versus crystalloid coload during spinal anesthesia for cesarean delivery: a randomized controlled trial.
        Anesth Analg. 2019; 128: 304-312
        • Odekon L.
        • Landau R.
        • Blouin J.L.
        • Brodow D.
        • Wang S.
        • Smiley R.M.
        The effect of beta2-adrenoceptor genotype on phenylephrine dose administered during spinal anesthesia for cesarean delivery.
        Anesth Analg. 2015; 120: 1309-1316
        • Landau R.
        • Liu S.K.
        • Blouin J.L.
        • Smiley R.M.
        • Ngan Kee W.D.
        The effect of maternal and fetal beta2-adrenoceptor and nitric oxide synthase genotype on vasopressor requirement and fetal acid-base status during spinal anesthesia for cesarean delivery.
        Anesth Analg. 2011; 112: 1432-1437
        • Papazian J.
        • Kacmar R.M.
        Obstetric hemorrhage: prevention, recognition, and treatment.
        Adv Anesth. 2017; 35: 65-93
        • Shen T.
        • Baker K.
        Venous return and clinical hemodynamics: how the body works during acute hemorrhage.
        Adv Physiol Educ. 2015; 39: 267-271
        • Kinsella S.M.
        • Carvalho B.
        • Dyer R.A.
        • et al.
        International consensus statement on the management of hypotension with vasopressors during caesarean section under spinal anaesthesia.
        Anaesthesia. 2018; 73: 71-92
        • Sporkova A.
        • Perez-Rivera A.
        • Galligan J.J.
        Interaction between alpha(1)- and alpha(2)-adrenoreceptors contributes to enhanced constrictor effects of norepinephrine in mesenteric veins compared to arteries.
        Eur J Pharmacol. 2010; 643: 239-246
        • Lee A.
        • Ngan Kee W.D.
        • Gin T.
        A quantitative, systematic review of randomized controlled trials of ephedrine versus phenylephrine for the management of hypotension during spinal anesthesia for cesarean delivery.
        Anesth Analg. 2002; 94: 920-926
        • Greiss Jr., F.C.
        Differential reactivity of the myoendometrial and placental vasculatures: adrenergic responses.
        Am J Obstet Gynecol. 1972; 112: 20-30
        • Goertz A.W.
        • Hubner C.
        • Seefelder C.
        • et al.
        The effect of ephedrine bolus administration on left ventricular loading and systolic performance during high thoracic epidural anesthesia combined with general anesthesia.
        Anesth Analg. 1994; 78: 101-105
        • Kobayashi S.
        • Endou M.
        • Sakuraya F.
        • et al.
        The sympathomimetic actions of l-ephedrine and d-pseudoephedrine: direct receptor activation or norepinephrine release?.
        Anesth Analg. 2003; 97: 1239-1245
        • Ralston D.H.
        • Shnider S.M.
        • DeLorimier A.A.
        Effects of equipotent ephedrine, metaraminol, mephentermine, and methoxamine on uterine blood flow in the pregnant ewe.
        Anesthesiology. 1974; 40: 354-370
        • Wang S.Y.
        • Datta S.
        • Segal S.
        Pregnancy alters adrenergic mechanisms in uterine arterioles of rats.
        Anesth Analg. 2002; 94: 1304-1309
        • Ngan Kee W.D.
        • Khaw K.S.
        • Lee B.B.
        • Lau T.K.
        • Gin T.
        A dose-response study of prophylactic intravenous ephedrine for the prevention of hypotension during spinal anesthesia for cesarean delivery.
        Anesth Analg. 2000; 90: 1390-1395
        • Ngan Kee W.D.
        • Khaw K.S.
        • Tan P.E.
        • Ng F.F.
        • Karmakar M.K.
        Placental transfer and fetal metabolic effects of phenylephrine and ephedrine during spinal anesthesia for cesarean delivery.
        Anesthesiology. 2009; 111: 506-512
        • Enouri S.
        • Monteith G.
        • Johnson R.
        Functional characteristics of alpha adrenergic and endothelinergic receptors in pressurized rat mesenteric veins.
        Can J Physiol Pharmacol. 2013; 91: 538-546
        • Rummery N.M.
        • Brock J.A.
        • Pakdeechote P.
        • Ralevic V.
        • Dunn W.R.
        ATP is the predominant sympathetic neurotransmitter in rat mesenteric arteries at high pressure.
        J Physiol. 2007; 582: 745-754
        • Anderson S.G.
        • Still J.G.
        • Greiss Jr., F.C.
        Differential reactivity of the gravid uterine vasculatures: effects of norepinephrine.
        Am J Obstet Gynecol. 1977; 129: 293-298
        • Ngan Kee W.D.
        • Lee S.W.
        • Ng F.F.
        • Tan P.E.
        • Khaw K.S.
        Randomized double-blinded comparison of norepinephrine and phenylephrine for maintenance of blood pressure during spinal anesthesia for cesarean delivery.
        Anesthesiology. 2015; 122: 736-745
        • Wang T.
        • He Q.
        • Zhang W.
        • et al.
        Determination of the ED50 and ED95 of intravenous bolus of norepinephrine for the treatment of hypotension during spinal anesthesia for cesarean delivery.
        Exp Ther Med. 2020; 19: 1763-1770
        • Fu F.
        • Xiao F.
        • Chen W.
        • et al.
        A randomised double-blind dose-response study of weight-adjusted infusions of norepinephrine for preventing hypotension during combined spinal-epidural anaesthesia for Caesarean delivery.
        Br J Anaesth. 2020; 124: e108-e114
        • Chen Y.
        • Zou L.
        • Li Z.
        • et al.
        Prophylactic norepinephrine infusion for postspinal anesthesia hypotension in patients undergoing cesarean section: A randomized, controlled, dose-finding trial.
        Pharmacotherapy. 2021; 41: 370-378
        • Michard F.
        • Teboul J.L.
        Predicting fluid responsiveness in ICU patients: a critical analysis of the evidence.
        Chest. 2002; 121: 2000-2008
        • Gelman S.
        Venous Circulation: A few challenging concepts in goal-directed hemodynamic therapy (GDHT).
        in: Farag E. Kurz A. Troianos C. Perioperative fluid management. Springer Nature, Switzerland2020: 365-385
        • Gelman S.
        • Bigatello L.
        The physiologic basis for goal-directed hemodynamic and fluid therapy: the pivotal role of the venous circulation.
        Can J Anaesth. 2018; 65: 294-308
        • Magder S.
        Understanding central venous pressure: not a preload index?.
        Curr Opin Crit Care. 2015; 21: 369-375
        • Westphal M.
        • James M.F.
        • Kozek-Langenecker S.
        • Stocker R.
        • Guidet B.
        • Van Aken H.
        Hydroxyethyl starches: different products-different effects.
        Anesthesiology. 2009; 111: 187-202
        • Mercier F.J.
        Fluid loading for cesarean delivery under spinal anesthesia: have we studied all the options?.
        Anesth Analg. 2011; 113: 677-680
        • Morgan P.J.
        • Halpern S.H.
        • Tarshis J.
        The effects of an increase of central blood volume before spinal anesthesia for cesarean delivery: a qualitative systematic review.
        Anesth Analg. 2001; 92: 997-1005
        • Chooi C.
        • Cox J.J.
        • Lumb R.S.
        • et al.
        Techniques for preventing hypotension during spinal anaesthesia for caesarean section.
        Cochrane Database Syst Rev. 2017; 8: CD002251
        • Ueyama H.
        • He Y.L.
        • Tanigami H.
        • Mashimo T.
        • Yoshiya I.
        Effects of crystalloid and colloid preload on blood volume in the parturient undergoing spinal anesthesia for elective Cesarean section.
        Anesthesiology. 1999; 91: 1571-1576
        • Ewaldsson C.A.
        • Hahn R.G.
        Volume kinetics of Ringer's solution during induction of spinal and general anaesthesia.
        Br J Anaesth. 2001; 87: 406-414
        • Dyer R.A.
        • Farina Z.
        • Joubert I.A.
        • et al.
        Crystalloid preload versus rapid crystalloid administration after induction of spinal anaesthesia (coload) for elective caesarean section.
        Anaesth Intensive Care. 2004; 32: 351-357
        • Ngan Kee W.D.
        • Khaw K.S.
        • Ng F.F.
        Prevention of hypotension during spinal anesthesia for cesarean delivery: an effective technique using combination phenylephrine infusion and crystalloid cohydration.
        Anesthesiology. 2005; 103: 744-750
        • McDonald S.
        • Fernando R.
        • Ashpole K.
        • Columb M.
        Maternal cardiac output changes after crystalloid or colloid coload following spinal anesthesia for elective cesarean delivery: a randomized controlled trial.
        Anesth Analg. 2011; 113: 803-810
        • Siddik-Sayyid S.M.
        • Nasr V.G.
        • Taha S.K.
        • et al.
        A randomized trial comparing colloid preload to coload during spinal anesthesia for elective cesarean delivery.
        Anesth Analg. 2009; 109: 1219-1224
        • Cluver C.
        • Novikova N.
        • Hofmeyr G.J.
        • Hall D.R.
        Maternal position during caesarean section for preventing maternal and neonatal complications.
        Cochrane Database Syst Rev. 2013; 3: CD007623
        • Sundararajan M.
        • Ravindran C.
        • Ponnusamy R.
        • Murugesan R.
        Prophylactic norepinephrine infusion or leg wrapping for postspinal hypotension in elective caesarean delivery: A randomised, double-blind, placebo-controlled trial.
        Eur J Anaesthesiol. 2020; 37: 803-809
        • Kuhn J.C.
        • Hauge T.H.
        • Rosseland L.A.
        • Dahl V.
        • Langesaeter E.
        Hemodynamics of phenylephrine infusion versus lower extremity compression during spinal anesthesia for cesarean delivery: a randomized, double-blind, placebo-controlled study.
        Anesth Analg. 2016; 122: 1120-1129
        • American College of O, Gynecologists
        • Task Force on Hypertension in P. Hypertension in pregnancy
        Report of the American College of Obstetricians and Gynecologists' Task Force on Hypertension in Pregnancy.
        Obstet Gynecol. 2013; 122: 1122-1131
      1. Mark AL. Structural changes in resistance and capacitance vessels in borderline hypertension. Hypertension 1984; 6: III 69-73.

        • Simon G.
        Altered venous function in hypertensive rats.
        Circ Res. 1976; 38: 412-418
        • Safar M.E.
        • London G.M.
        Venous system in essential hypertension.
        Clin Sci (Lond). 1985; 69: 497-504
        • Martin D.S.
        • Rodrigo M.C.
        • Appelt C.W.
        Venous tone in the developmental stages of spontaneous hypertension.
        Hypertension. 1998; 31: 139-144
        • Simmons L.A.
        • Gillin A.G.
        • Jeremy R.W.
        Structural and functional changes in left ventricle during normotensive and preeclamptic pregnancy.
        Am J Physiol Heart Circ Physiol. 2002; 283: H1627-1633
        • Dennis A.T.
        Transthoracic echocardiography in women with preeclampsia.
        Curr Opin Anaesthesiol. 2015; 28: 254-260
        • Gyselaers W.
        • Tomsin K.
        • Staelens A.
        • Mesens T.
        • Oben J.
        • Molenberghs G.
        Maternal venous hemodynamics in gestational hypertension and preeclampsia.
        BMC Pregnancy Childbirth. 2014; 14: 212
        • Vonck S.
        • Staelens A.S.
        • Lanssens D.
        • et al.
        Development of a biophysical screening model for gestational hypertensive diseases.
        J Biomed Sci. 2019; 26: 38
        • Scott G.
        • Gillon T.E.
        • Pels A.
        • von Dadelszen P.
        • Magee L.A.
        Guidelines-similarities and dissimilarities: a systematic review of international clinical practice guidelines for pregnancy hypertension.
        Am J Obstet Gynecol. 2022; 226: S1222-S1236
        • Blackman D.J.
        • Morris-Thurgood J.A.
        • Atherton J.J.
        • et al.
        Endothelium-derived nitric oxide contributes to the regulation of venous tone in humans.
        Circulation. 2000; 101: 165-170
        • Ogilvie R.I.
        Comparative effects of vasodilator drugs on flow distribution and venous return.
        Can J Physiol Pharmacol. 1985; 63: 1345-1355
        • Belfort M.A.
        • Saade G.R.
        • Suresh M.
        • Johnson D.
        • Vedernikov Y.P.
        Human umbilical vessels: responses to agents frequently used in obstetric patients.
        Am J Obstet Gynecol. 1995; 172: 1395-1403
        • Skajaa K.
        • Svane D.
        • Andersson K.E.
        • Forman A.
        Effects of magnesium and isradipine on contractile activation induced by the thromboxane A2 analog U46619 in human uteroplacental arteries in term pregnancy.
        Am J Obstet Gynecol. 1990; 163: 1323-1333
        • do Vale G.T.
        • Ceron C.S.
        • Gonzaga N.A.
        • Simplicio J.A.
        • Padovan J.C.
        Three generations of beta-blockers: history, class differences and clinical applicability.
        Curr Hypertens Rev. 2019; 15: 22-31
        • Jouppila P.
        • Kirkinen P.
        • Koivula A.
        • Ylikorkala O.
        Labetalol does not alter the placental and fetal blood flow or maternal prostanoids in pre-eclampsia.
        Br J Obstet Gynaecol. 1986; 93: 543-547
        • Shepherd A.M.
        • Irvine N.A.
        Differential hemodynamic and sympathoadrenal effects of sodium nitroprusside and hydralazine in hypertensive subjects.
        J Cardiovasc Pharmacol. 1986; 8: 527-533
        • D'Oyley H.M.
        • Tabrizchi R.
        • Pang C.C.
        Effects of vasodilator drugs on venous tone in conscious rats.
        Eur J Pharmacol. 1989; 162: 337-344
        • Waite R.P.
        • Pang C.C.
        • Walker M.J.
        Effects of calcium antagonists on mean circulatory filling pressure in the conscious rat.
        J Cardiovasc Pharmacol. 1988; 12: 499-504
        • Chen N.
        • Lv J.
        • Bo L.
        • et al.
        Muscarinic-mediated vasoconstriction in human, rat and sheep umbilical cords and related vasoconstriction mechanisms.
        BJOG. 2015; 122: 1630-1639
        • Robinson B.F.
        • Dobbs R.J.
        • Kelsey C.R.
        Effects of nifedipine on resistance vessels, arteries and veins in man.
        Br J Clin Pharmacol. 1980; 10: 433-438
        • Kiowski W.
        • Erne P.
        • Bertel O.
        • Bolli P.
        • Buhler F.
        Acute and chronic sympathetic reflex activation and antihypertensive response to nifedipine.
        J Am Coll Cardiol. 1986; 7: 344-348
        • David M.
        • Walka M.M.
        • Schmid B.
        • Sinha P.
        • Veit S.
        • Lichtenegger W.
        Nitroglycerin application during cesarean delivery: plasma levels, fetal/maternal ratio of nitroglycerin, and effects in newborns.
        Am J Obstet Gynecol. 2000; 182: 955-961
        • Ito H.H.S.
        Effects of vasodilators on the systemic capacitance vessels, a study with the measurement of the mean circulatory pressure in dogs.
        Jpn Circ J. 1984; 48: 388-404
        • Nonaka K.
        • Ueno A.
        Systemic study of the hemodynamic effects of sublingual nitroglycerin in unanesthetized dogs.
        Arch Int Pharmacodyn Ther. 1991; 312: 5-26
        • Gerson J.I.
        • Allen F.B.
        • Seltzer J.L.
        • Parker Jr., F.B.
        • Markowitz A.H.
        Arterial and venous dilation by nitroprusside and nitroglycerin–is there a difference?.
        Anesth Analg. 1982; 61: 256-260
        • Tabrizchi R.
        • Pang C.C.
        Effects of drugs on body venous tone, as reflected by mean circulatory filling pressure.
        Cardiovasc Res. 1992; 26: 443-448
        • Abdelrahman A.
        • Pang C.C.
        Differential venous effects of isoprenaline in conscious rats.
        Eur J Pharmacol. 1990; 190: 321-327
        • Coupar I.M.
        The effect of isoprenaline on adrenoceptors in human saphenous vein.
        Br J Pharmacol. 1970; 39: 465-475
        • Beck J.R.
        • Nadasdi M.
        • Zsoter T.T.
        Adrenergic receptors in human veins.
        Can Med Assoc J. 1970; 102: 1297-1299
        • Landau R.
        • Dishy V.
        • Wood A.J.
        • Stein C.M.
        • Smiley R.M.
        Disproportionate decrease in alpha- compared with beta-adrenergic sensitivity in the dorsal hand vein in pregnancy favors vasodilation.
        Circulation. 2002; 106: 1116-1120
        • Landau R.
        • Scott J.A.
        • Smiley R.M.
        Magnesium-induced vasodilation in the dorsal hand vein.
        BJOG. 2004; 111: 446-451
        • Aisenbrey G.A.
        • Corwin E.
        • Catanzarite V.
        Effect of magnesium sulfate on the vascular actions of norepinephrine and angiotensin II.
        Am J Perinatol. 1992; 9: 477-480
        • Vincent Jr., R.D.
        • Chestnut D.H.
        • Sipes S.L.
        • Weiner C.P.
        • DeBruyn C.S.
        • Bleuer S.A.
        Magnesium sulfate decreases maternal blood pressure but not uterine blood flow during epidural anesthesia in gravid ewes.
        Anesthesiology. 1991; 74: 77-82