Skip to main content
SpringerLink
Log in

Intravenous loading of nitroglycerin during rewarming of cardiopulmonary bypass improves metabolic homeostasis in cardiac surgery: a retrospective analysis

  • Original Article
  • Published:
Journal of Anesthesia Aims and scope Submit manuscript

Abstract

Purpose

The aim of the study was to evaluate the effects of high-dose nitroglycerine (NTG) on glucose metabolism, tissue oxygenation and postoperative recovery in cardiac surgical patients.

Methods

Cardiac surgical patients in the retrospective survey were classified into two groups based on the NTG regimen. NTG group had intravenous loading of NTG (infusion rate 10–20 mg/h with total dose of ≥0.5 mg/kg) starting at rewarming of cardiopulmonary bypass (CPB) (n = 101), and control group had no intravenous loading of NTG (n = 151). Data for intraoperative plasma glucose and lactate levels, and regular insulin consumption were collected. Propensity score methodology was utilized to adjust for potential confounders.

Results

After adjustment for propensity score, the plasma glucose was significantly lower in the NTG group during (161 ± 39 versus 179 ± 45 mg/dl, p = 0.005) and after CPB (167 ± 41 versus 184 ± 48 mg/dl, p = 0.012). Total consumption of regular insulin was significantly lower in the NTG group, median 8 (range 0–50) versus 13 (0–90) international units, p = 0.005. There was a trend towards statistical significance in a lower incidence of hyperlactatemia (>2.2 mmol/l) in the NTG group during CPB, 21/100 (21 %) versus 40/132 (30.3 %), p = 0.065. The mixed venous oxygen saturation in the intensive care unit was higher in the NTG group, 65 ± 9 versus 62 ± 11 %, p = 0.056.

Conclusions

Intravenous loading of NTG during and after CPB is safe and effective for attenuating the hyperglycemic response and reduce the incidence of hyperlactatemia during cardiac surgery with CPB.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Koning NJ, Vonk AB, Meesters MI, Oomens T, Verkaik M, Jansen EK, Baufreton C, Boer C. Microcirculatory perfusion is preserved during off-pump but not on-pump cardiac surgery. J Cardiothorac Vasc Anesth. 2014;28:336–41.

    Article  PubMed  Google Scholar 

  2. Atasever B, Boer C, Goedhart P, Biervliet J, Seyffert J, Speekenbrink R, Schwarte L, de Mol B, Ince C. Distinct alterations in sublingual microcirculatory blood flow and hemoglobin oxygenation in on-pump and off-pump coronary artery bypass graft surgery. J Cardiothorac Vasc Anesth. 2011;25:784–90.

    Article  PubMed  Google Scholar 

  3. De Backer D, Dubois MJ, Schmartz D, Koch M, Ducart A, Barvais L, Vincent JL. Microcirculatory alterations in cardiac surgery: effects of cardiopulmonary bypass and anesthesia. Ann Thorac Surg. 2009;88:1396–403.

    Article  PubMed  Google Scholar 

  4. Bauer A, Kofler S, Thiel M, Eifert S, Christ F. Monitoring of the sublingual microcirculation in cardiac surgery using orthogonal polarization spectral imaging: preliminary results. Anesthesiology. 2007;107:939–45.

    Article  PubMed  Google Scholar 

  5. Krinsley JS, Grover A. Severe hypoglycemia in critically ill patients: risk factors and outcomes. Crit Care Med. 2007;35:2262–7.

    Article  PubMed  Google Scholar 

  6. Thorell A, Nygren J, Ljungqvist O. Insulin resistance: a marker of surgical stress. Curr Opin Clin Nutr Metab Care. 1999;2:69–78.

    Article  CAS  PubMed  Google Scholar 

  7. den Uil CA, Caliskan K, Lagrand WK, van der Ent M, Jewbali LS, van Kuijk JP, Spronk PE, Simoons ML. Dose-dependent benefit of nitroglycerin on microcirculation of patients with severe heart failure. Intensive Care Med. 2009;35:1893–9.

    Article  Google Scholar 

  8. den Uil CA, Lagrand WK, Spronk PE, van der Ent M, Jewbali LS, Brugts JJ, Ince C, Simoons ML. Low-dose nitroglycerin improves microcirculation in hospitalized patients with acute heart failure. Eur J Heart Fail. 2009;11:386–90.

    Article  Google Scholar 

  9. Lima A, van Genderen ME, van Bommel J, Klijn E, Jansem T, Bakker J. Nitroglycerin reverts clinical manifestations of poor peripheral perfusion in patients with circulatory shock. Crit Care. 2014;18:R126.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Hatsuoka S, Sakamoto T, Stock UA, Nagashima M, Mayer JE Jr. Effect of l-arginine or nitroglycerine during deep hypothermic circulatory arrest in neonatal lambs. Ann Thorac Surg. 2003;75:197–203.

    Article  PubMed  Google Scholar 

  11. Cepeda MS, Boston R, Farrar JT, Strom BL. Comparison of logistic regression versus propensity score when the number of events is low and there are multiple confounders. Am J Epidemiol. 2003;158:280–7.

    Article  PubMed  Google Scholar 

  12. Anand KJ, Hansen DD, Hickey PR. Hormonal-metabolic stress responses in neonates undergoing cardiac surgery. Anesthesiology. 1990;73:661–70.

    Article  CAS  PubMed  Google Scholar 

  13. van den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, Vlasselaers D, Ferdinande P, Lauwers P, Bouillon R. Intensive insulin therapy in critically ill patients. N Engl J Med. 2001;345:1359–67.

    Article  PubMed  Google Scholar 

  14. Qaseem A, Humphrey LL, Chou R, Snow V, Shekelle P, Clinical Guidelines Committee of the American College of Physicians. Use of intensive insulin therapy for the management of glycemic control in hospitalized patients: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2011;154:260–7.

    Article  PubMed  Google Scholar 

  15. Bucerius J, Gummert JF, Walther T, Doll N, Falk V, Onnasch JF, Barten MJ, Mohr FW. Impact of diabetes mellitus on cardiac surgery outcome. Thorac Cardiovasc Surg. 2003;51:11–6.

    Article  CAS  PubMed  Google Scholar 

  16. Boyle EM Jr, Lille ST, Allaire E, Clowes AW, Verrier ED. Endothelial cell injury in cardiovascular surgery: atherosclerosis. Ann Thorac Surg. 1997;63:885–94.

    Article  PubMed  Google Scholar 

  17. Sellke FW, Boyle EM Jr, Verrier ED. Endothelial cell injury in cardiovascular surgery: the pathophysiology of vasomotor dysfunction. Ann Thorac Surg. 1996;62:1222–8.

    Article  CAS  PubMed  Google Scholar 

  18. Kovacs P, Szilvassy Z, Hegyi P, Nemeth J, Ferdinandy P, Tosaki A. Effect of transdermal nitroglycerin on glucose-stimulated insulin release in healthy male volunteers. Eur J Clin Invest. 2000;30:41–4.

    Article  CAS  PubMed  Google Scholar 

  19. Jedrzkiewicz S, Parker JD. Acute and chronic effects of glyceryl trinitrate therapy on insulin and glucose regulation in humans. J Cardiovasc Pharmacol Ther. 2013;18:211–6.

    Article  CAS  PubMed  Google Scholar 

  20. Fox-Robichaud A, Payne D, Hasan SU, Ostrovsky L, Fairhead T, Reinhardt P, Kubes P. Inhaled NO as a viable antiadhesive therapy for ischemia/reperfusion injury of distal microvascular beds. J Clin Invest. 1998;101:2497–505.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Nevière R, Guery B, Mordon S, Zerimech F, Charré S, Wattel F, Chopin C. Inhaled NO reduces leukocyte-endothelial cell interactions and myocardial dysfunction in endotoxemic rats. Am J Physiol Heart Circ Physiol. 2000;278:H1783–90.

    PubMed  Google Scholar 

  22. Liu X, Huang Y, Pokreisz P, Vermeersch P, Marsboom G, Swinnen M, Verbeken E, Santos J, Pellens M, Gillijns H, Van de Werf F, Bloch KD, Janssens S. Nitric oxide inhalation improves microvascular flow and decreases infarction size after myocardial ischemia and reperfusion. J Am Coll Cardiol. 2007;50:808–17.

    Article  PubMed  Google Scholar 

  23. Yu B, Raher MJ, Volpato GP, Bloch KD, Ichinose F, Zapol WM. Inhaled nitric oxide enables artificial blood transfusion without hypertension. Circulation. 2008;117:1982–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Baron DM, Yu B, Lei C, Bagchi A, Beloiartsev A, Stowell CP, Steinbicker AU, Malhotra R, Bloch KD, Zapol WM. Pulmonary hypertension in lambs transfused with stored blood is prevented by breathing nitric oxide. Anesthesiology. 2012;116:637–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Duncan HP, Cloote A, Weir PM, Jenkins I, Murphy PJ, Pawade AK, Rogers CA, Wolf AR. Reducing stress responses in the pre-bypass phase of open heart surgery in infants and young children: a comparison of different fentanyl doses. Br J Anaesth. 2000;84:556–64.

    Article  CAS  PubMed  Google Scholar 

  26. Bakker J, Gris P, Coffernils M, Kahn RJ, Vincent JL. Serial blood lactate levels can predict the development of multiple organ failure following septic shock. Am J Surg. 1996;171:221–6.

    Article  CAS  PubMed  Google Scholar 

  27. Jansen TC, van Bommel J, Woodward R, Mulder PG, Bakker J. Association between blood lactate levels, sequential organ failure assessment subscores, and 28-day mortality during early and late intensive care unit stay: a retrospective observational study. Crit Care Med. 2009;37:2369–74.

    Article  CAS  PubMed  Google Scholar 

  28. Fall PJ, Szerlip HM. Lactic acidosis: from sour milk to septic shock. J Intensive Care Med. 2005;20:255–71.

    Article  PubMed  Google Scholar 

  29. McNelis J, Marini CP, Jurkiewicz A, Szomstein S, Simms HH, Ritter G, Nathan IM. Prolonged lactate clearance is associated with increased mortality in the surgical intensive care unit. Am J Surg. 2001;182:481–5.

    Article  CAS  PubMed  Google Scholar 

  30. Arnold RC, Shapiro NI, Jones AE, Schorr C, Pope J, Casner E, Parrillo JE, Dellinger RP, Trzeciak S, Emergency Medicine Shock Research Network (EMShockNet) Investigators. Multicenter study of early lactate clearance as a determinant of survival in patients with presumed sepsis. Shock. 2009;32:35–9.

    Article  CAS  PubMed  Google Scholar 

  31. Pearse R, Dawson D, Fawcett J, Rhodes A, Grounds RM, Bennett ED. Changes in central venous saturation after major surgery, and association with outcome. Crit Care. 2005;9:R694–9.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Pölönen P, Ruokonen E, Hippeläinen M, Pöyhönen M, Takala J. A prospective, randomized study of goal-oriented hemodynamic therapy in cardiac surgical patients. Anesth Analg. 2000;90:1052–9.

    Article  PubMed  Google Scholar 

  33. Howard RJ, Crain C, Franzini DA, Hood CI, Hugli TE. Effects of cardiopulmonary bypass on pulmonary leukostasis and complement activation. Arch Surg. 1988;123:1496–501.

    Article  CAS  PubMed  Google Scholar 

  34. McGowan FX Jr, Ikegami M, del Nido PJ, Motoyama EK, Kurland G, Davis PJ, Siewers RD. Cardiopulmonary bypass significantly reduces surfactant activity in children. J Thorac Cardiovasc Surg. 1993;106:968–77.

    PubMed  Google Scholar 

  35. Bin JP, Doctor A, Lindner J, Hendersen EM, Le DE, Leong-Poi H, Fisher NG, Christiansen J, Kaul S. Effects of nitroglycerin on erythrocyte rheology and oxygen unloading: novel role of S-nitrosohemoglobin in relieving myocardial ischemia. Circulation. 2006;113:2502–8.

    Article  CAS  PubMed  Google Scholar 

  36. Skrzypchak AM, Lafayette NG, Bartlett RH, Zhou Z, Frost MC, Meyerhoff ME, Reynolds MM, Annich GM. Effect of varying nitric oxide release to prevent platelet consumption and preserve platelet function in an in vivo model of extracorporeal circulation. Perfusion. 2007;22:193–200.

    Article  PubMed  Google Scholar 

  37. Martins e Silva J, Saldanha C. Arterial endothelium and atherothrombogenesis—intact endothelium in vascular and blood homeostasis. Rev Port Cardiol. 2006;25:1061–83.

    PubMed  Google Scholar 

  38. Pye M, Oldroyd KG, Conkie JA, Hutton I, Cobbe SM. A clinical and in vitro study on the possible interaction of intravenous nitrates with heparin anticoagulation. Clin Cardiol. 1994;17:658–61.

    Article  CAS  PubMed  Google Scholar 

  39. Koh KK, Park GS, Song JH, Moon TH, In HH, Kim JJ, Lee HJ, Cho SK, Kim SS. Interaction of intravenous heparin and organic nitrates in acute ischemic syndromes. Am J Cardiol. 1995;76:706–9.

    Article  CAS  PubMed  Google Scholar 

  40. Vermeulen Windsant IC, de Wit NC, Sertorio JT, Beckers EA, Tanus-Santos JE, Jacobs MJ, Buurman WA. Blood transfusions increase circulating plasma free hemoglobin levels and plasma nitric oxide consumption: a prospective observational pilot study. Crit Care. 2012;16:R95.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Gaies MG, Gurney JG, Yen AH, Napoli ML, Gajarski RJ, Ohye RG, Charpie JR, Hirsch JC. Vasoactive-inotropic score as a predictor of morbidity and mortality in infants after cardiopulmonary bypass. Pediatr Crit Care Med. 2010;11:234–8.

    Article  PubMed  Google Scholar 

  42. Arnold RC, Dellinger RP, Parrillo JE, Chansky ME, Lotano VE, McCoy JV, Jones AE, Shapiro NI, Hollenberg SM, Trzeciak S. Discordance between microcirculatory alterations and arterial pressure in patients with hemodynamic instability. J Crit Care. 2012;27:531.e1–537.e1.

    Article  Google Scholar 

  43. Boerma EC, Ince C. The role of vasoactive agents in the resuscitation of microvascular perfusion and tissue oxygenation in critically ill patients. Intensive Care Med. 2010;36:2004–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. De Backer D, Creteur J, Dubois MJ, Sakr Y, Koch M, Verdant C, Vincent JL. The effects of dobutamine on microcirculatory alterations in patients with septic shock are independent of its systemic effects. Crit Care Med. 2006;34:403–8.

    Article  PubMed  Google Scholar 

  45. Atasever B, Boer C, van der Kuil M, Lust E, Beishuizen A, Speekenbrink R, Seyffert J, de Mol B, Ince C. Quantitative imaging of microcirculatory response during nitroglycerin-induced hypotension. J Cardiothorac Vasc Anesth. 2011;25:140–4.

    Article  PubMed  Google Scholar 

  46. Hogue CW Jr, Palin CA, Arrowsmith JE. Cardiopulmonary bypass management and neurologic outcomes: an evidence-based appraisal of current practices. Anesth Analg. 2006;103:21–37.

    Article  PubMed  Google Scholar 

  47. Maier S, Hasibeder WR, Hengl C, Pajk W, Schwarz B, Margreiter J, Ulmer H, Engl J, Knotzer H. Effects of phenylephrine on the sublingual microcirculation during cardiopulmonary bypass. Br J Anaesth. 2009;102:485–91.

    Article  CAS  PubMed  Google Scholar 

  48. Spronk PE, Ince C, Gardien MJ, Mathura KR, Oudemans-van Straaten HM, Zandstra DF. Nitroglycerin in septic shock after intravascular volume resuscitation. Lancet. 2002;360:1395–6.

    Article  PubMed  Google Scholar 

  49. Boerma EC, Koopmans M, Konijn A, Kaiferova K, Bakker AJ, van Roon EN, Buter H, Bruins N, Egbers PH, Gerritsen RT, Koetsier PM, Kingma WP, Kuiper MA, Ince C. 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. 2010;38:93–100.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

YHT contributed to data collection and manuscript drafting. KYC contributed to statistical review. SWL assisted in study design. CCL, KCC and CCS helped manage and care for the patients. CCL and STH were involved in revising the manuscript critically for important intellectual content. MYT gave final approval of the version to be published and agreed to be accountable for ensuring the accuracy or integrity of the work. All authors read and approved the final manuscript.

Author information

Authors and Affiliations

  1. Department of Surgery, Taipei Veterans General Hospital, Yuanshan Branch, Yilan, Taiwan

    Ying-Hsuan Tai

  2. Department of Anesthesiology, Taipei Veterans General Hospital, No. 201, Sec. 2, Shih-pai Rd., Taipei, 11217, Taiwan

    Ying-Hsuan Tai, Kuang-Yi Chang, Shu-Wei Liao, Shung-Tai Ho, Chih-Cherng Lu & Mei-Yung Tsou

  3. Department of Nursing, Taipei Veterans General Hospital, Taipei, Taiwan

    Kwei-Chun Chung

  4. Division of Cardiovascular Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan

    Chun-Che Shih

Authors
  1. Ying-Hsuan Tai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kuang-Yi Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shu-Wei Liao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kwei-Chun Chung
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chun-Che Shih
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shung-Tai Ho
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Chih-Cherng Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Mei-Yung Tsou
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mei-Yung Tsou.

Ethics declarations

Conflict of interest

There are no financial or other relationships to disclose that might lead to a conflict of interest regarding this article.

Appendix

Appendix

See Table 5.

Table 5 The results of propensity score analysis
Full size table

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tai, YH., Chang, KY., Liao, SW. et al. Intravenous loading of nitroglycerin during rewarming of cardiopulmonary bypass improves metabolic homeostasis in cardiac surgery: a retrospective analysis. J Anesth 30, 779–788 (2016). https://doi.org/10.1007/s00540-016-2207-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00540-016-2207-0

Keywords

Search

Navigation