Log in | Register

The role of vasoactive agents in the resuscitation of microvascular perfusion and tissue oxygenation in critically ill patientsOpen access

E. Christiaan Boerma| Can Ince
Review
Volume 36, Issue 12 / December , 2010

Pages 2004 - 2018

Abstract

Purpose

The clinical use of vasoactive drugs is not only intended to improve systemic hemodynamic variables, but ultimately to attenuate derangements in organ perfusion and oxygenation during shock. This review aims (1) to discuss basic physiology with respect to manipulating vascular tone and its effect on the microcirculation, and (2) to provide an overview of available clinical data on the relation between vasoactive drugs and organ perfusion, with specific attention paid to recent developments that have enabled direct in vivo observation of the microcirculation and concepts that have originated from it.

Methods

A MedLine search was conducted for clinical articles in the English language over the last 15 years pertainig to shock, sepsis, organ failure, or critically ill patients in combination with vasoactive drugs and specific variables of organ perfusion/oxygenation (e.g., tonometry, indocyanine clearance, laser Doppler, and sidestream dark field imaging).

Results

Eighty original papers evaluating the specific relationship between organ perfusion/oxygenation and the use of vasoactive drugs were identified and are discussed in light of physiological theory of vasomotor tone.

Conclusions

Solid clinical data in support of the idea that increasing blood pressure in shock improves microcirculatory perfusion/oxygenation seem to be lacking, and such a concept might not be in line with physiological theory of microcirculation as a low-pressure vascular compartment. In septic shock no beneficial effect on microcirculatory perfusion above a mean arterial pressure of 65 mmHg has been reported, but a wide range in inter-individual effect seems to exist. Whether improvement of microcirculatory perfusion is associated with better patient outcome remains to be elucidated.

Keywords

References

  1. Vincent JL, International Sepsis Forum (2001) Hemodynamic support in septic shock. Intensive Care Med 27(Suppl 1):S80–S92
  2. Weil MH, Shubin H (1971) Proposed reclassification of shock states with special reference to distributive defects. Adv Exp Med Biol 23:13–23
    • View reference on PubMed
  3. Ince C, Ashruf JF, Avontuur JA, Wieringa PA, Spaan JA, Bruining HA (1993) Heterogeneity of the hypoxic state in rat heart is determined at capillary level. Am J Physiol 264:H294–H301
    • View reference on PubMed
  4. Dubin A, Edul VSK, Pozo MO et al (2008) Persistent villi hypoperfusion explains intramucosal acidosis in sheep endotoxemia. Crit Care Med 36:535–542. doi:10.1097/01.CCM.0000300083.74726.43
    • View reference on publisher's website
    • View reference on PubMed
  5. Buwalda M, Ince C (2002) Opening the microcirculation: can vasodilators be useful in sepsis? Intensive Care Med 28:1208–1217. doi:10.1007/s00134-002-1407-2
  6. Mongardon N, Dyson A, Singer M (2009) Is MOF an outcome parameter or a transient, adaptive state in critical illness? Curr Opin Crit Care 15:431–436. doi:10.1097/MCC.0b013e3283307a3b
    • View reference on publisher's website
    • View reference on PubMed
  7. 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 5:1209–1212. doi:10.1038/13529
    • View reference on publisher's website
    • View reference on PubMed
  8. Trzeciak S, Dellinger RP, Parrillo JE et al (2007) Early microcirculatory perfusion derangements in patients with severe sepsis and septic shock: relationship to hemodynamics, oxygen transport, and survival. Ann Emerg Med 49:88–98, 98.e1–2. doi:10.1016/j.annemergmed.2006.08.021
  9. Boerma EC, van der Voort PHJ, Spronk PE, Ince C (2007) Relationship between sublingual and intestinal microcirculatory perfusion in patients with abdominal sepsis. Crit Care Med 35:1055–1060. doi:10.1097/01.CCM.0000259527.89927.F9
    • View reference on publisher's website
    • View reference on PubMed
  10. 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 32:1825–1831
    • View reference on publisher's website
    • View reference on PubMed
  11. Jhanji S, Lee C, Watson D, Hinds C, Pearse RM (2009) Microvascular flow and tissue oxygenation after major abdominal surgery: association with post-operative complications. Intensive Care Med 35:671–677. doi:10.1007/s00134-008-1325-z
  12. Dellinger RP, Levy MM, Carlet JM et al (2008) Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Intensive Care Med 34:17–60. doi:10.1007/s00134-007-0934-2
  13. Ince C (2005) The microcirculation is the motor of sepsis. Crit Care 9(Suppl 4):S13–S19. doi:10.1186/cc3753
  14. Pries AR, Secomb TW, Gaehtgens P (1996) Biophysical aspects of blood flow in the microvasculature. Cardiovasc Res 32:654–667
    • View reference on PubMed
  15. Segal SS (2005) Regulation of blood flow in the microcirculation. Microcirculation 12:33–45. doi:10.1080/10739680590895028
    • View reference on publisher's website
    • View reference on PubMed
  16. Stamler JS, Jia L, Eu JP, McMahon TJ, Demchenko IT, Bonaventura J, Gernert K, Piantadosi CA (1997) Blood flow regulation by S-nitrosohemoglobin in the physiological oxygen gradient. Science 276:2034–2037
    • View reference on publisher's website
    • View reference on PubMed
  17. Taylor AE, Moore TM (1999) Capillary fluid exchange. Am J Physiol 277:S203–S210
    • View reference on PubMed
  18. Fahraeus R (1929) The suspension stability of the blood. Physiol Rev 1929:241–271
  19. Krogh A (1921) Studies on the physiology of capillaries: II. The reactions to local stimuli of the blood-vessels in the skin and web of the frog. J Physiol 55:412–422
    • View reference on PubMed
  20. Duling BR, Desjardins C (1987) Capillary hematocrit–what does it mean. News Physiol Sci 1987:66–69
  21. Delaunay A, Lebrun J, Delaunay M (1948) Le mode d’action des endotoxines bactériennes IV.Les troubles vase-moteurs chez les animaux intoxiqués et leurs conséquences. J Physiol Paris 40:89–110
  22. Bhagat K, Collier J, Vallance P (1996) Local venous responses to endotoxin in humans. Circulation 94:490–497
    • View reference on PubMed
  23. Sayk F, Vietheer A, Schaaf B, Wellhoener P, Weitz G, Lehnert H, Dodt C (2008) Endotoxemia causes central downregulation of sympathetic vasomotor tone in healthy humans. Am J Physiol Regul Integr Comp Physiol 295:R891–R898. doi:10.1152/ajpregu.90444.2008
    • View reference on PubMed
  24. Martin C, Viviand X, Leone M, Thirion X (2000) Effect of norepinephrine on the outcome of septic shock. Crit Care Med 28:2758–2765
    • View reference on publisher's website
    • View reference on PubMed
  25. Dubin A, Pozo MO, Casabella CA, Palizas F, Murias G, Moseinco MC, Kanoore Edul VS, Estenssoro E, Ince C (2009) Increasing arterial blood pressure with norepinephrine does not improve microcirculatory blood flow: a prospective study. Crit Care 13:R92. doi:10.1186/cc7922
    • View reference on publisher's website
    • View reference on PubMed
  26. Jhanji S, Stirling S, Patel N, Hinds CJ, Pearse RM (2009) The effect of increasing doses of norepinephrine on tissue oxygenation and microvascular flow in patients with septic shock*. Crit Care Med 37:1961–1966. doi:10.1097/CCM.0b013e3181a00a1c
  27. LeDoux D, Astiz ME, Carpati CM, Rackow EC (2000) Effects of perfusion pressure on tissue perfusion in septic shock. Crit Care Med 28:2729–2732
    • View reference on publisher's website
    • View reference on PubMed
  28. Bourgoin A, Leone M, Delmas A, Garnier F, Albanèse J, Martin C (2005) Increasing mean arterial pressure in patients with septic shock: effects on oxygen variables and renal function. Crit Care Med 33:780–786
    • View reference on publisher's website
    • View reference on PubMed
  29. Albanèse J, Leone M, Garnier F, Bourgoin A, Antonini F, Martin C (2004) Renal effects of norepinephrine in septic and nonseptic patients. Chest 126:534–539. doi:10.1378/chest.126.2.534
    • View reference on publisher's website
    • View reference on PubMed
  30. Nakajima Y, Baudry N, Duranteau J, Vicaut E (2006) Effects of vasopressin, norepinephrine, and l-arginine on intestinal microcirculation in endotoxemia. Crit Care Med 34:1752–1757. doi:10.1097/01.CCM.0000218812.73741.6C
    • View reference on publisher's website
    • View reference on PubMed
  31. Deruddre S, Cheisson G, Mazoit JX, Vicaut E, Benhamou D, Duranteau J (2007) Renal arterial resistance in septic shock: effects of increasing mean arterial pressure with norepinephrine on the renal resistive index assessed with Doppler ultrasonography. Intensive Care Med 33:1557–1562. doi:10.1007/s00134-007-0665-4
  32. Myburgh JA, Higgins A, Jovanovska A, Lipman J, Ramakrishnan N, Santamaria J, CAT Study investigators (2008) A comparison of epinephrine and norepinephrine in critically ill patients. Intensive Care Med 34:2226–2234. doi:10.1007/s00134-008-1219-0
  33. Annane D, Vignon P, Renault A et al (2007) Norepinephrine plus dobutamine versus epinephrine alone for management of septic shock: a randomised trial. Lancet 370:676–684. doi:10.1016/S0140-6736(07)61344-0
    • View reference on publisher's website
    • View reference on PubMed
  34. Morelli A, Ertmer C, Rehberg S et al (2008) Phenylephrine versus norepinephrine for initial hemodynamic support of patients with septic shock: a randomized, controlled trial. Crit Care 12:R143. doi:10.1186/cc7121
    • View reference on publisher's website
    • View reference on PubMed
  35. De Backer D, Biston P, Devriendt J et al (2010) Comparison of dopamine and norepinephrine in the treatment of shock. N Engl J Med 362:779–789. doi:10.1056/NEJMoa0907118
    • View reference on publisher's website
    • View reference on PubMed
  36. Dünser MW, Takala J, Ulmer H et al (2009) Arterial blood pressure during early sepsis and outcome. Intensive Care Med 35:1225–1233. doi:10.1007/s00134-009-1427-2
  37. Dünser MW, Ruokonen E, Pettilä V, Ulmer H, Torgersen C, Schmittinger CA, Jakob S, Takala J (2009) Association of arterial blood pressure and vasopressor load with septic shock mortality: a post hoc analysis of a multicenter trial. Crit Care 13:R181. doi:10.1186/cc8167
    • View reference on publisher's website
    • View reference on PubMed
  38. Spahn DR, Cerny V, Coats TJ et al (2007) Management of bleeding following major trauma: a European guideline. Crit Care 11:R17. doi:10.1186/cc5686
    • View reference on publisher's website
    • View reference on PubMed
  39. Gowda RM, Fox JT, Khan IA (2008) Cardiogenic shock: basics and clinical considerations. Int J Cardiol 123:221–228. doi:10.1016/j.ijcard.2006.03.099
    • View reference on publisher's website
    • View reference on PubMed
  40. Jung C, Rödiger C, Fritzenwanger M, Schumm J, Lauten A, Figulla HR, Ferrari M (2009) Acute microflow changes after stop and restart of intra-aortic balloon pump in cardiogenic shock. Clin Res Cardiol 98:469–475. doi:10.1007/s00392-009-0018-0
    • View reference on publisher's website
    • View reference on PubMed
  41. Levy B, Gibot S, Franck P, Cravoisy A, Bollaert PE (2005) Relation between muscle Na+K+ ATPase activity and raised lactate concentrations in septic shock: a prospective study. Lancet 365:871–875. doi:10.1016/S0140-6736(05)71045-X
    • View reference on publisher's website
    • View reference on PubMed
  42. Meier-Hellmann A, Reinhart K, Bredle DL, Specht M, Spies CD, Hannemann L (1997) Epinephrine impairs splanchnic perfusion in septic shock. Crit Care Med 25:399–404
    • View reference on publisher's website
    • View reference on PubMed
  43. Uusaro A, Takala J (1998) Vasoactive drugs and splanchnic perfusion in septic shock. Crit Care Med 26:1458–1460
    • View reference on publisher's website
    • View reference on PubMed
  44. Morelli A, Lange M, Ertmer C et al (2008) Short-term effects of phenylephrine on systemic and regional hemodynamics in patients with septic shock: a crossover pilot study. Shock 29:446–451. doi:10.1097/shk.0b013e31815810ff
    • View reference on PubMed
  45. Maier S, Hasibeder WR, Hengl C, Pajk W, Schwarz B, Margreiter J, Ulmer H, Engl J, Knotzer H (2009) Effects of phenylephrine on the sublingual microcirculation during cardiopulmonary bypass. Br J Anaesth 102:485–491. doi:10.1093/bja/aep018
    • View reference on publisher's website
    • View reference on PubMed
  46. O’Dwyer C, Woodson LC, Conroy BP, Lin CY, Deyo DJ, Uchida T, Johnston WE (1997) Regional perfusion abnormalities with phenylephrine during normothermic bypass. Ann Thorac Surg 63:728–735
    • View reference on publisher's website
    • View reference on PubMed
  47. Landry DW, Oliver JA (2001) The pathogenesis of vasodilatory shock. N Engl J Med 345:588–595
    • View reference on publisher's website
    • View reference on PubMed
  48. Dünser MW, Mayr AJ, Ulmer H, Knotzer H, Sumann G, Pajk W, Friesenecker B, Hasibeder WR (2003) Arginine vasopressin in advanced vasodilatory shock: a prospective, randomized, controlled study. Circulation 107:2313–2319. doi:10.1161/01.CIR.0000066692.71008.BB
    • View reference on publisher's website
    • View reference on PubMed
  49. Dubois MJ, De Backer D, Creteur J, Anane S, Vincent JL (2003) Effect of vasopressin on sublingual microcirculation in a patient with distributive shock. Intensive Care Med 29:1020–1023. doi:10.1007/s00134-003-1742-y
    • View reference on PubMed
  50. Lauzier F, Lévy B, Lamarre P, Lesur O (2006) Vasopressin or norepinephrine in early hyperdynamic septic shock: a randomized clinical trial. Intensive Care Med 32:1782–1789. doi:10.1007/s00134-006-0378-0
  51. van Haren FMP, Rozendaal FW, van der Hoeven JG (2003) The effect of vasopressin on gastric perfusion in catecholamine-dependent patients in septic shock. Chest 124:2256–2260
    • View reference on publisher's website
    • View reference on PubMed
  52. Klinzing S, Simon M, Reinhart K, Bredle DL, Meier-Hellmann A (2003) High-dose vasopressin is not superior to norepinephrine in septic shock. Crit Care Med 31:2646–2650. doi:10.1097/01.CCM.0000094260.05266.F4
    • View reference on publisher's website
    • View reference on PubMed
  53. Asfar P, Bracht H, Radermacher P (2008) Impact of vasopressin analogues on the gut mucosal microcirculation. Best Pract Res Clin Anaesthesiol 22:351–358
    • View reference on publisher's website
    • View reference on PubMed
  54. Dünser MW, Mayr AJ, Tür A, Pajk W, Barbara F, Knotzer H, Ulmer H, Hasibeder WR (2003) Ischemic skin lesions as a complication of continuous vasopressin infusion in catecholamine-resistant vasodilatory shock: incidence and risk factors. Crit Care Med 31:1394–1398. doi:10.1097/01.CCM.0000059722.94182.79
    • View reference on publisher's website
    • View reference on PubMed
  55. Russell JA, Walley KR, Singer J et al (2008) Vasopressin versus norepinephrine infusion in patients with septic shock. N Engl J Med 358:877–887. doi:10.1056/NEJMoa067373
    • View reference on publisher's website
    • View reference on PubMed
  56. Nygren A, Thorén A, Ricksten SE (2009) Vasopressin decreases intestinal mucosal perfusion: a clinical study on cardiac surgery patients in vasodilatory shock. Acta Anaesthesiol Scand 53:581–588. doi:10.1111/j.1399-6576.2008.01900.x
    • View reference on publisher's website
    • View reference on PubMed
  57. Bragadottir G, Redfors B, Nygren A, Sellgren J, Ricksten SE (2009) Low-dose vasopressin increases glomerular filtration rate, but impairs renal oxygenation in post-cardiac surgery patients. Acta Anaesthesiol Scand 53:1052–1059. doi:10.1111/j.1399-6576.2009.02037.x
    • View reference on publisher's website
    • View reference on PubMed
  58. Ryckwaert F, Virsolvy A, Fort A, Murat B, Richard S, Guillon G, Colson PH (2009) Terlipressin, a provasopressin drug exhibits direct vasoconstrictor properties: consequences on heart perfusion and performance. Crit Care Med 37:876–881. doi:10.1097/CCM.0b013e31819b8199
    • View reference on publisher's website
    • View reference on PubMed
  59. O’Brien A, Clapp L, Singer M (2002) Terlipressin for norepinephrine-resistant septic shock. Lancet 359:1209–1210. doi:10.1016/S0140-6736(02)08225-9
    • View reference on publisher's website
    • View reference on PubMed
  60. Boerma EC, van der Voort PHJ, Ince C (2005) Sublingual microcirculatory flow is impaired by the vasopressin-analogue terlipressin in a patient with catecholamine-resistant septic shock. Acta Anaesthesiol Scand 49:1387–1390. doi:10.1111/j.1399-6576.2005.00752.x
    • View reference on publisher's website
    • View reference on PubMed
  61. Albanèse J, Leone M, Delmas A, Martin C (2005) Terlipressin or norepinephrine in hyperdynamic septic shock: a prospective, randomized study. Crit Care Med 33:1897–1902
    • View reference on publisher's website
    • View reference on PubMed
  62. Leone M, Albanèse J, Delmas A, Chaabane W, Garnier F, Martin C (2004) Terlipressin in catecholamine-resistant septic shock patients. Shock 22:314–319
    • View reference on publisher's website
    • View reference on PubMed
  63. Morelli A, Rocco M, Conti G et al (2004) Effects of terlipressin on systemic and regional haemodynamics in catecholamine-treated hyperkinetic septic shock. Intensive Care Med 30:597–604. doi:10.1007/s00134-003-2094-3
  64. Mégarbané H, Barete S, Khosrotehrani K, Izzedine H, Moguelet P, Chosidow O, Frances C, Aractingi S (2009) Two observations raising questions about risk factors of cutaneous necrosis induced by terlipressin (Glypressin). Dermatology 218:334–337. doi:10.1159/000195676
    • View reference on publisher's website
    • View reference on PubMed
  65. Döhler KD, Meyer M (2008) Vasopressin analogues in the treatment of hepatorenal syndrome and gastrointestinal haemorrhage. Best Pract Res Clin Anaesthesiol 22:335–350
    • View reference on publisher's website
    • View reference on PubMed
  66. De Backer D, Creteur J, Dubois MJ, Sakr Y, Koch M, Verdant C, Vincent JL (2006) The effects of dobutamine on microcirculatory alterations in patients with septic shock are independent of its systemic effects. Crit Care Med 34:403–408
    • View reference on publisher's website
    • View reference on PubMed
  67. Nevière R, Mathieu D, Chagnon JL, Lebleu N, Wattel F (1996) The contrasting effects of dobutamine and dopamine on gastric mucosal perfusion in septic patients. Am J Respir Crit Care Med 154:1684–1688
    • View reference on PubMed
  68. Joly LM, Monchi M, Cariou A, Chiche JD, Bellenfant F, Brunet F, Dhainaut JF (1999) Effects of dobutamine on gastric mucosal perfusion and hepatic metabolism in patients with septic shock. Am J Respir Crit Care Med 160:1983–1986
    • View reference on PubMed
  69. Duranteau J, Sitbon P, Teboul JL, Vicaut E, Anguel N, Richard C, Samii K (1999) Effects of epinephrine, norepinephrine, or the combination of norepinephrine and dobutamine on gastric mucosa in septic shock. Crit Care Med 27:893–900
    • View reference on publisher's website
    • View reference on PubMed
  70. Reinelt H, Radermacher P, Fischer G, Geisser W, Wachter U, Wiedeck H, Georgieff M, Vogt J (1997) Effects of a dobutamine-induced increase in splanchnic blood flow on hepatic metabolic activity in patients with septic shock. Anesthesiology 86:818–824
    • View reference on publisher's website
    • View reference on PubMed
  71. Debaveye YA, Van den Berghe GH (2004) Is there still a place for dopamine in the modern intensive care unit? Anesth Analg 98:461–468
    • View reference on publisher's website
    • View reference on PubMed
  72. Meier-Hellmann A, Bredle DL, Specht M, Spies C, Hannemann L, Reinhart K (1997) The effects of low-dose dopamine on splanchnic blood flow and oxygen uptake in patients with septic shock. Intensive Care Med 23:31–37
  73. Olson D, Pohlman A, Hall JB (1996) Administration of low-dose dopamine to nonoliguric patients with sepsis syndrome does not raise intramucosal gastric pH nor improve creatinine clearance. Am J Respir Crit Care Med 154:1664–1670
    • View reference on PubMed
  74. Marik PE, Mohedin M (1994) The contrasting effects of dopamine and norepinephrine on systemic and splanchnic oxygen utilization in hyperdynamic sepsis. JAMA 272:1354–1357
    • View reference on publisher's website
    • View reference on PubMed
  75. Smithies M, Yee TH, Jackson L, Beale R, Bihari D (1994) Protecting the gut and the liver in the critically ill: effects of dopexamine. Crit Care Med 22:789–795
    • View reference on publisher's website
    • View reference on PubMed
  76. Temmesfeld-Wollbrück B, Szalay A, Mayer K, Olschewski H, Seeger W, Grimminger F (1998) Abnormalities of gastric mucosal oxygenation in septic shock: partial responsiveness to dopexamine. Am J Respir Crit Care Med 157:1586–1592
    • View reference on PubMed
  77. Seguin P, Laviolle B, Guinet P, Morel I, Mallédant Y, Bellissant E (2006) Dopexamine and norepinephrine versus epinephrine on gastric perfusion in patients with septic shock: a randomized study [NCT00134212]. Crit Care 10:R32. doi:10.1186/cc4827
    • View reference on publisher's website
    • View reference on PubMed
  78. Tenhunen JJ, Martikainen TJ, Uusaro A, Ruokonen E (2003) Dopexamine reverses colonic but not gastric mucosal perfusion defects in lethal endotoxin shock. Br J Anaesth 91:878–885
    • View reference on publisher's website
    • View reference on PubMed
  79. Gårdebäck M, Settergren G, Ohquist G, Tirén C (1995) Effect of dopexamine on calculated low gastric intramucosal pH following valve replacement. Acta Anaesthesiol Scand 39:599–604
    • View reference on publisher's website
    • View reference on PubMed
  80. Uusaro A, Ruokonen E, Takala J (1995) Gastric mucosal pH does not reflect changes in splanchnic blood flow after cardiac surgery. Br J Anaesth 74:149–154
    • View reference on publisher's website
    • View reference on PubMed
  81. Pearse RM, Belsey JD, Cole JN, Bennett ED (2008) Effect of dopexamine infusion on mortality following major surgery: individual patient data meta-regression analysis of published clinical trials. Crit Care Med 36:1323–1329. doi:10.1097/CCM.0b013e31816a091b
    • View reference on publisher's website
    • View reference on PubMed
  82. Gopal S, Jayakumar D, Nelson PN (2009) Meta-analysis on the effect of dopexamine on in-hospital mortality. Anaesthesia 64:589–594. doi:10.1111/j.1365-2044.2009.05896.x
    • View reference on publisher's website
    • View reference on PubMed
  83. Morelli A, De Castro S, Teboul JL et al (2005) Effects of levosimendan on systemic and regional hemodynamics in septic myocardial depression. Intensive Care Med 31:638–644. doi:10.1007/s00134-005-2619-z
  84. Leppikangas H, Tenhunen JJ, Lindgren L, Salenius JP, Ruokonen E (2008) Effects of levosimendan on indocyanine green plasma disappearance rate and the gastric mucosal-arterial pCO2 gradient in abdominal aortic aneurysm surgery. Acta Anaesthesiol Scand 52:785–792. doi:10.1111/j.1399-6576.2008.01659.x
    • View reference on publisher's website
    • View reference on PubMed
  85. Fries M, Ince C, Rossaint R, Bleilevens C, Bickenbach J, Rex S, Mik EG (2008) Levosimendan but not norepinephrine improves microvascular oxygenation during experimental septic shock. Crit Care Med 36:1886–1891. doi:10.1097/CCM.0b013e31817cede9
    • View reference on publisher's website
    • View reference on PubMed
  86. Münzel T, Wenzel P, Daiber A (2007) Do we still need organic nitrates? J Am Coll Cardiol 49:1296–1298. doi:10.1016/j.jacc.2007.01.007
    • View reference on publisher's website
    • View reference on PubMed
  87. Trzeciak S, Cinel I, Phillip Dellinger R, Shapiro NI, Arnold RC, Parrillo JE, Hollenberg SM, Microcirculatory Alterations in Resuscitation, Shock (MARS) Investigators (2008) Resuscitating the microcirculation in sepsis: the central role of nitric oxide, emerging concepts for novel therapies, and challenges for clinical trials. Acad Emerg Med 15:399–413. doi:10.1111/j.1553-2712.2008.00109.x
    • View reference on publisher's website
    • View reference on PubMed
  88. Bakker J, Grover R, McLuckie A et al (2004) Administration of the nitric oxide synthase inhibitor NG-methyl-l-arginine hydrochloride (546C88) by intravenous infusion for up to 72 hours can promote the resolution of shock in patients with severe sepsis: results of a randomized, double-blind, placebo-controlled multicenter study (study no. 144-002). Crit Care Med 32:1–12. doi:10.1097/01.CCM.0000105118.66983.19
  89. López A, Lorente JA, Steingrub J et al (2004) Multiple-center, randomized, placebo-controlled, double-blind study of the nitric oxide synthase inhibitor 546C88: effect on survival in patients with septic shock. Crit Care Med 32:21–30. doi:10.1097/01.CCM.0000105581.01815.C6
    • View reference on publisher's website
    • View reference on PubMed
  90. Moppett IK, Sherman RW, Wild MJ, Latter JA, Mahajan RP (2008) Effects of norepinephrine and glyceryl trinitrate on cerebral haemodynamics: transcranial Doppler study in healthy volunteers. Br J Anaesth 100:240–244. doi:10.1093/bja/aem374
    • View reference on publisher's website
    • View reference on PubMed
  91. Spronk PE, Ince C, Gardien MJ, Mathura KR, Oudemans-van Straaten HM, Zandstra DF (2002) Nitroglycerin in septic shock after intravascular volume resuscitation. Lancet 360:1395–1396
    • View reference on publisher's website
    • View reference on PubMed
  92. Boerma EC, Koopmans M, Konijn A et al (2010) Effects of nitroglycerin on sublingual microcirculatory blood flow in patients with severe sepsis/septic shock after a strict resuscitation protocol: a double-blind randomized placebo controlled trial. Crit Care Med 38:93–100. doi:10.1097/CCM.0b013e3181b02fc1
    • View reference on publisher's website
    • View reference on PubMed
  93. De Backer D, Creteur J, Dubois MJ, Sakr Y, Vincent JL (2004) Microvascular alterations in patients with acute severe heart failure and cardiogenic shock. Am Heart J 147:91–99
    • View reference on publisher's website
    • View reference on PubMed
  94. den Uil CA, Lagrand WK, Spronk PE, van der Ent M, Jewbali LSD, Brugts JJ, Ince C, Simoons ML (2009) Low-dose nitroglycerin improves microcirculation in hospitalized patients with acute heart failure. Eur J Heart Fail 11:386–390. doi:10.1093/eurjhf/hfp021
    • View reference on publisher's website
  95. Lam K, Sjauw KD, Henriques JPS, Ince C, de Mol BA (2009) Improved microcirculation in patients with an acute ST-elevation myocardial infarction treated with the Impella LP2.5 percutaneous left ventricular assist device. Clin Res Cardiol 98:311–318. doi:10.1007/s00392-009-0006-4
  96. Buise MP, Ince C, Tilanus HW, Klein J, Gommers D, van Bommel J (2005) The effect of nitroglycerin on microvascular perfusion and oxygenation during gastric tube reconstruction. Anesth Analg 100:1107–1111. doi:10.1213/01.ANE.0000147665.60613.CA
    • View reference on publisher's website
    • View reference on PubMed
  97. Buise M, van Bommel J, Jahn A, Tran K, Tilanus H, Gommers D (2006) Intravenous nitroglycerin does not preserve gastric microcirculation during gastric tube reconstruction: a randomized controlled trial. Crit Care 10:R131. doi:10.1186/cc5043
    • View reference on publisher's website
    • View reference on PubMed
  98. Konishi M, Sakakura M, Tsushima N (1990) Effects of ketanserin on microhemodynamics and hemorheology in patients with essential hypertension. Cardiovasc Drugs Ther 4 Suppl 1:101–104
  99. Elbers PWG, Ozdemir A, van Iterson M, van Dongen EPA, Ince C (2009) Microcirculatory imaging in cardiac anesthesia: ketanserin reduces blood pressure but not perfused capillary density. J Cardiothorac Vasc Anesth 23:95–101. doi:10.1053/j.jvca.2008.09.013
    • View reference on publisher's website
    • View reference on PubMed
  100. Bihari D, Smithies M, Gimson A, Tinker J (1987) The effects of vasodilation with prostacyclin on oxygen delivery and uptake in critically ill patients. N Engl J Med 317:397–403
    • View reference on publisher's website
    • View reference on PubMed
  101. Scheeren T, Radermacher P (1997) Prostacyclin (PGI2): new aspects of an old substance in the treatment of critically ill patients. Intensive Care Med 23:146–158
  102. Radermacher P, Buhl R, Santak B, Klein M, Kniemeyer HW, Becker H, Tarnow J (1995) The effects of prostacyclin on gastric intramucosal pH in patients with septic shock. Intensive Care Med 21:414–421
  103. Eichelbrönner O, Reinelt H, Wiedeck H, Mezödy M, Rossaint R, Georgieff M, Radermacher P (1996) Aerosolized prostacyclin and inhaled nitric oxide in septic shock–different effects on splanchnic oxygenation? Intensive Care Med 22:880–887
  104. Nygren A, Thorén A, Houltz E, Ricksten SE (2006) Autoregulation of human jejunal mucosal perfusion during cardiopulmonary bypass. Anesth Analg 102:1617–1622. doi:10.1213/01.ANE.0000219596.34753.72
    • View reference on publisher's website
    • View reference on PubMed

Sign In

Connect with ICM

Top 5 Articles Editors Picks Supplement