Intensive Care Medicine

, Volume 36, Issue 8, pp 1299–1308 | Cite as

The impact of fluid therapy on microcirculation and tissue oxygenation in hypovolemic patients: a review




An optimal volume replacement strategy aims to restore systemic hemodynamics with the ultimate goals of improving organ perfusion and microcirculation for sustaining adequate tissue oxygenation. This review presents the (patho)physiological basis of hypovolemia, microcirculation, and tissue oxygenation and presents a literature review on the effects of plasma substitutes on microperfusion and oxygenation in the clinical setting.


Literature review of the effects of fluid therapy on microcirculation and tissue oxygenation using PubMed search including original papers in English from 1988 to 2009.


We identified a total of 14 articles dealing with the effects of different crystalloids and colloids on organ perfusion, microcirculation, and tissue oxygenation in patients. The results are divergent, but there is a general trend that colloids are superior to crystalloids in improving organ perfusion, microcirculation, and tissue oxygenation. Due to the limited number of studies and different study conditions, a meta-analysis on the effects of the volume replacement strategies on microcirculation is not possible.


Improving the microcirculation by volume replacement appears to be a promising issue when treating the critically ill. The growing insights from animal experiments have to be translated into the clinical setting to identify the optimal fluid regimen for correcting hypovolemia. New techniques for monitoring microcirculation at the bedside might provide such endpoints, although these have to be validated also in the clinical setting. Whether improved microperfusion and tissue oxygenation by fluid therapy will also improve patient outcomes will have to be proven by future studies.


Volume replacement Crystalloids Albumin Gelatins Hydroxyethyl starch Microcirculation Tissue oxygenation Patients 


  1. 1.
    Edouard AR, Degrémont AC, Duranteau J, Pussard E, Berdeaux A, Samii K (1994) Heterogeneous regional vascular responses to simulated transient hypovolemia in man. Intensive Care Med 20:220–414CrossRefGoogle Scholar
  2. 2.
    Ince C (2004) Microcirculation in distress: a new resuscitation end point? Crit Care Med 32:1963–1964CrossRefPubMedGoogle Scholar
  3. 3.
    Vollmar B, Menger MD (2004) Volume replacement and microhemodynamic changes in polytrauma. Langenbecks Arch Surg 389:485–491CrossRefPubMedGoogle Scholar
  4. 4.
    Perret C, Feihl F (2000) Volume expansion during septic shock. Bull Acad Natl Med 184:1621–1629PubMedGoogle Scholar
  5. 5.
    Sakr Y, Dubois MJ, De Backer D, Creteur J, Vincent JL (2004) Persistent microcirculatory alterations are associated with organ failure and death in patients with septic shock. Crit Care Med 32:1825–1831CrossRefPubMedGoogle Scholar
  6. 6.
    Takala J, Jakob SM (2009) Shedding light on microcirculation. Intensive Care Med 35:394–396CrossRefPubMedGoogle Scholar
  7. 7.
    Mythen MG, Salmon JB, Webb AR (1993) The rational administration of colloids. Blood Rev 7:223–228CrossRefPubMedGoogle Scholar
  8. 8.
    Weil MH, Shubin H (1971) Proposed reclassification of states of shock. Adv Exp Med Biol 23:13–23PubMedGoogle Scholar
  9. 9.
    Ince C (2005) The microcirculation is the motor of sepsis. Crit Care 9(Suppl 4):S13–S19CrossRefPubMedGoogle Scholar
  10. 10.
    De Backer D, Creteur J, Preiser JC, Dubois MJ, Vincent JL (2002) Microvascular blood flow is altered in patients with sepsis. Am J Respir Crit Care Med 166:98–104CrossRefPubMedGoogle Scholar
  11. 11.
    Vincent JL, Weil MH (2006) Fluid challenge revisited. Crit Care Med 34:1333–1337CrossRefPubMedGoogle Scholar
  12. 12.
    Van Bommel J, Siegemund M, Henny CP, Ince C (2008) Heart, kidney, and intestine have different tolerances for anemia. Transl Res 151:110–117CrossRefPubMedGoogle Scholar
  13. 13.
    Trzeciak S, Dellinger RP, Parrillo JE, Guglielmi M, Bajaj J, Abate NL (2007) Early microcirculatory perfusion derangements in patients with severe sepsis and septic shock: relationship to hemodynamics, oxygen transport, and survival. Ann Emerg Med 49:88–98CrossRefPubMedGoogle Scholar
  14. 14.
    Van Bommel J, Henny CP, Trouwborst A, Ince C (2001) Microvascular shunting in severe normovolemic hemodilution. Anesthesiology 94:152–160CrossRefPubMedGoogle Scholar
  15. 15.
    Wang P, Hauptman JG, Chaudry IH (1990) Hemorrhage produces depression in microvascular blood flow which persists despite fluid resuscitation. Circ Shock 32:307–318PubMedGoogle Scholar
  16. 16.
    Ehrly AM, Landgraf H (1985) Influence of intravenous infusions of hydroxyethylstarch (HES) (MW 40,000 and 450,000) on the blood flow properties of healthy volunteers. Angiology 36:41–44CrossRefPubMedGoogle Scholar
  17. 17.
    Boldt J (2007) The balanced concept of fluid resuscitation. Br J Anaesth 99:312–315CrossRefPubMedGoogle Scholar
  18. 18.
    Powell-Tuck J, Gosling P, Lobo DN, Allison SP, Carlson GL, Gore M, Lewington AJ, Pearse RM, Mythen MG (2008) British consensus guidelines on intravenous fluid therapy for adult surgical patients.
  19. 19.
    Kellum JA (2002) Fluid resuscitation and hyperchloremic acidosis in experimental sepsis: improved short-term survival and acid-base balance with Hextend compared with saline. Crit Care Med 30:300–305CrossRefPubMedGoogle Scholar
  20. 20.
    Scheingraber S, Rehm M, Sehmisch C, Finsterer U (1999) Rapid saline infusion produces hyperchloremic acidosis in patients undergoing gynecologic surgery. Anesthesiology 90:1265–1270CrossRefPubMedGoogle Scholar
  21. 21.
    Boldt J (2008) Saline versus balanced hydroxyethyl starch: does it matter? Curr Opin Anaesthesiol 21:679–683CrossRefPubMedGoogle Scholar
  22. 22.
    Boldt J (2006) Do plasma substitutes have additional properties beyond correcting volume deficits? Shock 25:103–116CrossRefPubMedGoogle Scholar
  23. 23.
    Kellum JA, Song M, Almasri E (2006) Hyperchloremic acidosis increases circulating inflammatory molecules in experimental sepsis. Chest 130:962–967CrossRefPubMedGoogle Scholar
  24. 24.
    Boldt J, Suttner S, Brosch C, Lehmann A, Röhm K, Mengistu A (2009) The influence of a balanced volume replacement concept on inflammation, endothelial activation, and kidney integrity in elderly cardiac surgery patients. Intensive Care Med 35:462–470CrossRefPubMedGoogle Scholar
  25. 25.
    Matharu NM, Butler LM, Rainger GE, Gosling P, Vohra RK, Nash GB (2008) Mechanisms of the anti-inflammatory effects of hydroxyethyl starch demonstrated in a flow-based model of neutrophil recruitment by endothelial cells. Crit Care Med 36:1536–1542CrossRefPubMedGoogle Scholar
  26. 26.
    Kaplan SS, Park TS, Gonzales ER, Gidday JM (2000) Hydroxyethyl starch reduces leukocyte adherence and vascular injury in the newborn pig cerebral circulation after asphyxia. Stroke 31:2218–2223PubMedGoogle Scholar
  27. 27.
    Kupper S, Torge Mees S, Gassmann P, Brodde M, Kehrel B, Haier J (2007) Hydroxyethyl starch normalizes platelet and leukocyte adhesion within pulmonary microcirculation during LPS-induced endotoxemia. Shock 28:300–308CrossRefPubMedGoogle Scholar
  28. 28.
    Inan N, Iltar S, Surer H, Yilmaz G, Alemdaroglu KB, Yazar MA, Basar H (2009) Effect of hydroxyethyl starch 130/0.4 on ischaemia/reperfusion in rabbit skeletal muscle. Eur J Anaesthesiol 26:160–165CrossRefPubMedGoogle Scholar
  29. 29.
    Funk W, Baldinger V (1995) Microcirculatory perfusion during volume therapy. A comparative study using crystalloid or colloid in awake animals. Anesthesiology 82:975–982CrossRefPubMedGoogle Scholar
  30. 30.
    Hoffmann JN, Vollmar B, Laschke MW, Inthorn D, Schildberg FW, Menger MD (2002) Hydroxyethyl starch (130 kD), but not crystalloid volume support, improves microcirculation during normotensive endotoxemia. Anesthesiology 97:460–470CrossRefPubMedGoogle Scholar
  31. 31.
    Rubio-Gayosso I, Platts SH, Duling BR (2006) Reactive oxygen species mediate modification of glycocalyx during ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol 290:H2247–H2256CrossRefPubMedGoogle Scholar
  32. 32.
    Chappell D, Jacob M, Hofmann-Kiefer K, Conzen P, Rehm M (2008) A rational approach to perioperative fluid management. Anesthesiology 109:723–740CrossRefPubMedGoogle Scholar
  33. 33.
    Constantinescu AA, Vink H, Spaan JA (2003) Endothelial cell glycocalyx modulates immobilization of leukocytes at the endothelial surface. Arterioscler Thromb Vasc Biol 23:1541–1547CrossRefPubMedGoogle Scholar
  34. 34.
    Mulivor AW, Lipowsky HH (2002) Role of glycocalyx in leukocyte-endothelial cell adhesion. Am J Physiol Heart 283:H1282–H1291Google Scholar
  35. 35.
    Rehm M, Zahler S, Lötsch M, Welsch U, Conzen P, Jacob M, Becker B (2004) Endothelial glycocalyx as an additional barrier determining extravasation of 6% hydroxyethyl starch or 5% albumin solutions in the coronary vascular bed. Anesthesiology 100:1211–1223CrossRefPubMedGoogle Scholar
  36. 36.
    Leslie SJ, Affolter J, Denvir MA, Webb DJ (2003) Validation of laser Doppler flowmetry coupled with intra-dermal injection for investigating effects of vasoactive agents on the skin microcirculation in man. Eur J Clin Pharmacol 59:99–102PubMedGoogle Scholar
  37. 37.
    Dubin A, Edul VSK, Ince C (2009) Determinants of tissue pCO2 in shock and sepsis: relationship to the microcirculation. In: Vincent JL (ed) Yearbook of intensive care and emergency medicine. Springer, Heidelberg, pp 195–204CrossRefGoogle Scholar
  38. 38.
    Russell JA (1997) Gastric tonometry: does it work? Intensive Care Med 23:3–6CrossRefPubMedGoogle Scholar
  39. 39.
    Vallet B, Lund N, Curtis S, Kelly D, Cain S (1994) Gut and muscle tissue PO2 in endotoxemic dogs during shock and resuscitation. J Appl Physiol 76:793–800PubMedGoogle Scholar
  40. 40.
    Dubin A, Edul VS, Pozo MO, Murias G, Canullan CM, Martins EF, Ferrara G, Canales HS, Laporte M, Estenssoro E, Ince C (2008) Persistent villi hypoperfusion explains intramucosal acidosis in sheep endotoxemia. Crit Care Med 36:535–542CrossRefPubMedGoogle Scholar
  41. 41.
    Creteur J, De Backer D, Sakr Y, Koch M, Vincent JL (2004) Sublingual capnometry tracks microcirculatory changes in septic patients. Crit Care Med 32:516–523Google Scholar
  42. 42.
    Weil MH, Nakagawa Y, Tang W, Sato Y, Ercoli F, Finegan R (1999) Sublingual capnometry: a new noninvasive measurement for diagnosis and quantification of severity of circulatory shock. Crit Care Med 27:1225–1229CrossRefPubMedGoogle Scholar
  43. 43.
    Goedhart PT, Khalilzada M, Bezemer R, Merza J, Ince C (2007) Sidestream dark field (SDF) imaging: a novel stroboscopic LED ring-based imaging modality for clinical assessment of the microcirculation. Opt Express 15:15101–15114CrossRefPubMedGoogle Scholar
  44. 44.
    Groner W, Winkelman JW, Harris AG, Ince C, Bouma GJ, Messmer K, Nadeau RG (1999) Orthogonal polarization spectral imaging: a new method for study of the microcirculation. Nat Med 5:1209–1212CrossRefPubMedGoogle Scholar
  45. 45.
    Clark LC (1956) Monitor and control of blood and tissue oxygen tension. Trans Am Soc Artif Intern Org 2:41–46Google Scholar
  46. 46.
    Jobsis FF (1977) Noninvasive, infrared monitoring of cerebral and myocardial oxygen sufficiency and circulatory parameters. Science 198:1264–1267CrossRefPubMedGoogle Scholar
  47. 47.
    Marik PE, Iglesias J, Maini B (1997) Gastric intramucosal pH changes after volume replacement with hydroxyethyl starch or crystalloid in patients undergoing elective abdominal aortic aneurysm repair. J Crit Care 12:51–55CrossRefPubMedGoogle Scholar
  48. 48.
    Guo X, Xu Z, Ren H, Luo A, Huang Y, Ye T (2003) Effect of volume replacement with hydroxyethyl starch solution on splanchnic oxygenation in patients undergoing cytoreductive surgery for ovarian cancer. Chin Med J 116:996–1000PubMedGoogle Scholar
  49. 49.
    Lang K, Boldt J, Suttner S, Haisch G (2001) Colloids versus crystalloids and tissue oxygen tension in patients undergoing major abdominal surgery. Anesth Analg 93:405–409CrossRefPubMedGoogle Scholar
  50. 50.
    Arkiliç C, Taguchi A, Sharma N, Ratnaraj J (2003) Supplemental perioperative fluid administration increases tissue oxygen pressure. Surgery 133:49–55CrossRefPubMedGoogle Scholar
  51. 51.
    Boldt J, Heesen M, Muller M, Pabsdorf M, Hempelmann G (1996) The effects of albumin versus hydroxyethyl starch solution on cardiorespiratory and circulatory variables in critically ill patients. Anesth Analg 83:254–261CrossRefPubMedGoogle Scholar
  52. 52.
    Boldt J, Zickmann B, Herold C, Ballesteros M, Dapper F, Hempelmann G (1991) Influence of hypertonic volume replacement on the microcirculation in cardiac surgery. Br J Anaesth 67:595–602CrossRefPubMedGoogle Scholar
  53. 53.
    Mythen MG, Webb AR (1995) Perioperative plasma volume expansion reduces the incidence of gut mucosal hypoperfusion during cardiac surgery. Ann Surg 130:423–429Google Scholar
  54. 54.
    Asfar P, Kerkeni N, Labadie F, Gouello JP, Brenet O, Alquier P (2000) Assessment of hemodynamic and gastric mucosal acidosis with modified fluid gelatin versus hydroxyethyl starch: a prospective, randomized study. Intensive Care Med 26:1282–1287CrossRefPubMedGoogle Scholar
  55. 55.
    Forrest DM, Baigorri F, Chittock DR, Spinelli JJ, Rusel JA (2000) Volume expansion using pentastarch does not change gastric-arterial PCO2 gradient or gastric intramucosal pHi in patients who have sepsis syndrome. Crit Care Med 28:2254–2258CrossRefPubMedGoogle Scholar
  56. 56.
    Rittoo D, Gosling P, Bonnici C, Burnley S, Millns P, Simms MH, Smith SR, Vohra RK (2002) Splanchnic oxygenation in patients undergoing abdominal aortic aneurysm repair and volume expansion with eloHAES. Cardiovasc Surg 10:128–133CrossRefPubMedGoogle Scholar
  57. 57.
    Hofmann D, Thuemer O, Schelenz C, van Hoot N, Sakka SG (2005) Increasing cardiac output by fluid loading: effects on indocyanine green plasma disappearance rate and splanchnic microcirculation. Acta Anaesthesiol Scand 49:1280–1286CrossRefPubMedGoogle Scholar
  58. 58.
    Mahmood A, Gosling P, Barclay R, Kilvington F, Vohra R (2009) Splanchnic microcirculation protection by hydroxyethyl starches during abdominal aortic aneurysm surgery. Eur J Vasc Endovasc Surg 37:319–325CrossRefPubMedGoogle Scholar
  59. 59.
    Wilkes NJ, Woolf R, Mutch M, Mallett SV, Peachey T, Stephens R, Mythen MG (2001) The effects of balanced versus saline-based hetastarch and crystalloid solutions on acid-base and electrolyte status and gastric mucosal perfusion in elderly surgical patients. Anesth Analg 93:811–816CrossRefPubMedGoogle Scholar
  60. 60.
    Kreimeier U, Bruckner UB, Niemczyk S, Messmer K (1990) Hyperosmotic saline dextran for resuscitation from traumatic-hemorrhagic hypotension: effect on regional blood flow. Circ Shock 32:83–99PubMedGoogle Scholar
  61. 61.
    Behrman SW, Fabian TC, Kudsk KA, Proctor KG (1991) Microcirculatory flow changes after initial resuscitation of hemorrhagic shock with 7.5% hypertonic saline/6% dextran 70. J Trauma 31:589–598CrossRefPubMedGoogle Scholar
  62. 62.
    Al-Rawi PG, Zygun D, Tseng MY, Hutchinson PJ, Matta BF, Kirkpatrick PJ (2005) Cerebral blood flow augmentation in patients with severe subarachnoid haemorrhage. Acta Neurochir (Suppl) 95:123–127CrossRefGoogle Scholar

Copyright information

© Copyright jointly held by Springer and ESICM 2010

Authors and Affiliations

  1. 1.Department of Anesthesiology and Intensive Care MedicineKlinikum der Stadt LudwigshafenLudwigshafenGermany
  2. 2.Department of Intensive CareErasmus MC University Hospital RotterdamRotterdamThe Netherlands

Personalised recommendations