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Short-term effects of methylene blue on hemodynamics and gas exchange in humans with septic shock

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Abstract

Objective

The aim of this study was to investigate the acute effects of methylene blue (MB), an inhibitor of thel-arginine nitric oxide pathway, in patients with septic shock.

Design

A prospective, open, single-dose study.

Setting

The medical ICU of a university hospital.

Patients

Six patients with severe septic shock.

Interventions

Complete hemodynamic values were recorded before and 20 min after the infusion of intravenous MB (3 mg kg−1). Arterial pressure was then monitored during the next 24 h or until death.

Measurements and results

Methylene blue increased the mean arterial pressure from 69.7±4.5 to 83.7±5.1 mmHg (p=0.028) and the mean pulmonary artery pressure, from 34.3±7.2 to 38.7±8.0 mmHg (p=0.023). Systemic vascular resistance index was increased from 703.1±120.6 to 903.7±152.2 dyne.s.cm−5.m−2 (p=0.028) and pulmonary vascular resistance index, from 254.6±96.9 to 342.2±118.9 dyne.s.cm−5.m−2 (p=0.027). The PaO2/FIO2 decreased from 229.2±54.4 to 162.2±44.1 mmHg (p=0.028), without significant modification of intrapulmonary shunting. Heart rate, cardiac index, right atrial pressure, DO2, VO2, oxygen extraction and arterial lactate were essentially unchanged. Sequential measurements of arterial pressure demonstrated a return to baseline level in 2–3 h. All but one patients died, three in shock and two in multiple organ failure.

Conclusions

MB induces systemic and pulmonary vasoconstriction in patients with septic shock, without significant decrease in cardiac index. The worsening of arterial oxygenation following MB injection may limit its use in patients with the adult respiratory distress syndrome. Larger studies are required to determine whether MB improves the outcome of patients with septic shock.

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References

  1. Parker MM, Shelhamer JH, Natanson C, Alling D, Parillo JE (1987) Serial hemodynamic patterns in survivors and non-survivors of septic shock in humans. Crit Care Med 15: 923–929

    PubMed  Google Scholar 

  2. Lowenstein CJ, Dinerman JL, Snyder SH (1994) Nitric oxide: a physiologic messenger. Ann Intern Med 120: 227–237

    PubMed  Google Scholar 

  3. Moncada S, Higgs A (1993) Thel-arginine-nitric oxide pathway. N Engl J Med 329: 2002–2012

    PubMed  Google Scholar 

  4. Clutton-Brock J (1967) Two cases of poisoning by contamination of nitrous oxide with higher oxides of nitrogen during anaesthesia. J Anaesth 39: 388–392

    Google Scholar 

  5. Hall HA, Kulig KW, Rumack BH (1986) Drug and chemical-induced methaemo-globinaemia: clinical features and management. Med Toxicol 1: 253–260

    PubMed  Google Scholar 

  6. Mayer B, Brunner F, Schmidt K (1993) Inhibition of nitric oxide synthesis by methylene blue. Biochem Pharmacol 45: 367–374

    PubMed  Google Scholar 

  7. Henry Y, Lepoivre M, Drapier JC, Ducrocq C, Boucher JL, Guissani A (1993) EPR characterization of molecular targets for NO in mammalian cells and organelles. FASEB J 7: 1124–1134

    PubMed  Google Scholar 

  8. Julou-Schaeffer G, Gray GA, Fleming I, Schott C, Parratt JR, Stoclet JC (1990) Loss of vascular responsiveness induced by endotoxin involvesl-arginine pathway. Am J Physiol 259: H1038-H1043

    PubMed  Google Scholar 

  9. Fleming I, Gray GA, Julou-Schaeffer G, Parratt JR, Stoclet JC (1990) Incubation with endotoxin activates thel-arginine pathway in vascular tissues. Biochem Biophys Res Commun 171: 562–568

    PubMed  Google Scholar 

  10. Paya D, Gray GA, Stoclet JC (1993) Effects of methylene blue on blood pressure and reactivity to norepinephrine in endotoxemic rats. J Cardiovasc Pharmacol 21: 926–930

    PubMed  Google Scholar 

  11. Preiser JC, Zhang H, Vincent JL (1994) Administration of methylene blue in septic shock: is it beneficial? In: Vincent JL (ed) Yearbook of intensive care and emergency medicine. Springer, Berlin Heidelberg New York, pp 90–100

    Google Scholar 

  12. Schneider F, Lutun P, Hasselmann M, Stoclet JC, Tempé JD (1992) Methylene blue increases systemic vascular resistance in human septic shock. Intensive Care Med 18: 309–311

    PubMed  Google Scholar 

  13. Le Gall JR, Loirat P, Alperovitch A, et al (1984) A simplified acute physiology score for ICU patients. Crit Care Med 12: 975–977

    PubMed  Google Scholar 

  14. Bone RC, Balk RA, Cerra FB, et al (1992) Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Chest 101: 1644–1662

    PubMed  Google Scholar 

  15. Knaus WA, Wagner DP, Draper EA, Zimmerman JE (1985) Prognosis in acute organ system failure. Ann Surg 202: 685–692

    PubMed  Google Scholar 

  16. Murray JF, Matthay MA, Luce JM, Flick MR (1988) An expanded definition of the adult respiratory distress syndrome. Am Rev Respir Dis 138: 720–723

    PubMed  Google Scholar 

  17. Tran DD, Groeneveld ABJ, Van der Meulen J, Nauta JJP, Strack Van Schijndel RJM, Thijs LG (1990) Age, chronic disease, sepsis, organ system failure, and mortality in a medical intensive care unit. Crit Care Med 18: 474–479

    PubMed  Google Scholar 

  18. Klabunde RE, Ritger RC (1991) NG-monomethyl-l-arginine (NMA) restores arterial blood pressure but reduces cardiac output in a canine model of endotoxic shock. Biochem Biophys Res Commun 178: 1135–1140

    PubMed  Google Scholar 

  19. Cobb JP, Natanson C, Hoffman WD et al (1992) Nω-amino-l-arginine, an inhibitor of nitric oxide synthase, raises vascular resistance but increases mortality rates in awake canines challenged with endotoxin. J Exp Med 176: 1175–1182

    PubMed  Google Scholar 

  20. Lorente JA, Landin L, Renes E, et al (1993) Role of nitric oxide in the hemodynamic changes of sepsis. Crit Care Med 21: 759–767

    PubMed  Google Scholar 

  21. Statman R, Cheng W, Cunningham JN, et al (1994) Nitric oxide inhibition in the treatment of the sepsis syndrome is detrimental to tissue oxygenation. J Surg Res 57: 93–98

    PubMed  Google Scholar 

  22. Schilling J, Cakmakci M, Battig U, Geroulanos S (1993) A new approach in the treatment of hypotension in human septic shock by NG-monomethyl-l-arginine, an inhibitor of the nitric oxide synthetase. Intensive Care Med 19: 227–231

    PubMed  Google Scholar 

  23. Lorente JA, Landin L, De Pablo R, Renes E, Liste D (1993)l-Arginine pathway in the sepsis syndrome. Crit Care Med 21: 1287–1295

    PubMed  Google Scholar 

  24. Petros A, Lamb G, Leone A, Moncada S, Bennett D, Vallance P (1994) Effects of a nitric oxide synthase inhibitor in humans with septic shock. Cardiovasc Res 28: 34–39

    PubMed  Google Scholar 

  25. Wright CE, Rees DD, Moncada S (1992) Protective and pathological roles of nitric oxide in endotoxin shock. Cardiovasc Res 26: 48–57

    PubMed  Google Scholar 

  26. Hutcheson IR, Whittle BJR, Boughton-Smith NK (1990) Role of nitric oxide in maintaining vascular integrity in endotoxin-induced acute intestinal damage in the rat. Br J Pharmacol 101: 815–820

    PubMed  Google Scholar 

  27. Harbrecht BG, Billiar TR, Stadler J, et al (1992) Nitric oxide synthesis serves to reduce hepatic damage during acute murine endotoxemia. Crit Care Med 20: 1568–1574

    PubMed  Google Scholar 

  28. Shultz PJ, Raij L (1992) Endogenously synthesized nitric oxide prevents endotoxin-induced glomerular thrombosis. J Clin Invest 90: 1718–1725

    PubMed  Google Scholar 

  29. Robinson DN, McFadzean WA (1990) Pulse oxymetry and methylene blue. Anesthesia 45: 884–885

    Google Scholar 

  30. Rossaint R, Falke KJ, Lopez F, Slama K, Pison U, Zapol WM (1993) Inhaled nitric oxide for the adult respiratory distress syndrome. N Engl J Med 328: 399–405

    PubMed  Google Scholar 

  31. Högman M, Frostell CG, Hedenström H, Hedenstierna H (1993) Inhalation of nitric oxide modulates adult human bronchial tone. Am Rev Respir Dis 148: 1474–1478

    PubMed  Google Scholar 

  32. Midgley S, Grant IS, Haynes WG, Webb DJ (1991) Nitric oxide in liver failure. Lancet 338: 1590

    Google Scholar 

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Additional information

The study was supported by the Délégation à la Recherche Clinique, Assistance Publique-Hôpitaux de Paris

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Gachot, B., Bédos, J.P., Veber, B. et al. Short-term effects of methylene blue on hemodynamics and gas exchange in humans with septic shock. Intensive Care Med 21, 1027–1031 (1995). https://doi.org/10.1007/BF01700666

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  • DOI: https://doi.org/10.1007/BF01700666

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