Skip to main content

Vasopressors and inotropes in cardiogenic shock: is there room for “adrenaline resuscitation”?

The Original Article was published on 04 July 2016

We read with interest the paper of Tarvasmäki et al. [1] regarding the role of inotropes and vasopressors in patients with cardiogenic shock. The authors should be congratulated for their effort of prospectively collecting a huge amount of data in one of the most challenging settings. However, too much emphasis seems to be placed on the authors’ conclusions, especially taking into account some of the study’s limitations.

Right from the start of the paper, a fearsome association between adrenaline and short-term mortality in the generic setting of cardiogenic shock is described. However, up to 80 % of the patients enrolled in the study had an acute coronary syndrome as the cause leading to shock and this should have been emphasized [2].

Adrenaline doses (maximum infusion rate 0.22 mcg/kg/min (interquartile range 0.10–0.36)) were abnormally high. It is well known that, depending on vascular beds and concentration, adrenaline may induce either vascular dilatation or contraction, with the vasopressor effects arising at higher doses [3]. These effects might be extremely amplified when coupled with other vasopressors, leading to impaired organ functions. In this study, patients receiving adrenaline were also more likely to receive higher doses of noradrenaline and dopamine.

Furthermore, patients receiving adrenaline were more frequently resuscitated prior to admission, had a higher incidence of low output state, and worse renal function at admission. A more frequent recourse to a mechanical assist device was also present in these patients. Considering the small sample size (40 patients received adrenaline), might propensity score and multivariable analysis take account of all these confounding and effect modifiers? It is well known that researchers should use extreme caution when interpreting the results of analyses performed including a propensity score as a covariate in a multivariable model [4].

Looking at the unadjusted odds ratios reported in their Fig. 1 [1], we were impressed by the confidence intervals. Levosimendan was used in 52 patients: this sample is small but the effect estimation is accurate because these patients were, presumably, clinically selected. Noradrenaline was used in 162 patients: this sample is larger but the effect estimation is less accurate because, supposedly, these patients were a more heterogeneous group. What about the patients receiving adrenaline? Were they at the extreme spectrum of the population enrolled?

We believe there is not enough evidence to promote a link between adrenaline administration and increased death rates. Conversely, low to mid doses of vasopressors might be considered part of an integrated approach but only when massive myocardial damage has not yet occurred.

Authors’ response to “Vasopressors and inotropes in cardiogenic shock: is there room for ‘adrenaline resuscitation’?”

We thank Morici and colleagues for their interest in our paper and acknowledging our work. They point out that most patients in our study had cardiogenic shock (CS) caused by acute coronary syndrome. This is clearly stated in the results and also described in the previously published paper on the characteristics and outcome of this prospectively enrolled cohort of CS [5].

The dose of adrenaline and concomitant use of other vasopressors and inotropes may indeed be subject to variation according to local experience and practices. In a contemporary randomized controlled trial in CS, IABP-SHOCK II, the median dose of adrenaline was 0.3 μg/kg/min (Table S1 in the Supplementary Appendix of [6]), which is very similar to the dose recorded in the CardShock study. However, the association of adrenaline with mortality was not dependent on the doses of other vasopressors. The characteristics of patients treated with and without adrenaline are also shown in Table 1 in our paper [1] and mortality analyses were adjusted for differences. Mechanical assist devices other than an intra-aortic balloon pump were used in very few patients overall.

We are aware of the limitations regarding propensity score adjustment. Therefore, we performed additional propensity score matching as a sensitivity analysis, which confirmed the finding. In addition, further adjustment with the use of intra-aortic balloon pump or other mechanical assist devices did not change the results. While the study population is of limited size and the estimates of treatment effects may be susceptible to bias by unknown or unmeasured variables, we think that the results are consistent. All in all, while our study does not prove causality, it does raise safety concerns about using adrenaline in CS.

Abbreviations

CS:

Cardiogenic shock

References

  1. Tarvasmäki T, Lassus J, Varpula M, Sionis A, Sund R, Køber L, Spinar J, Parissis J, Banaszewski M, Silva Cardoso J, Carubelli V, Di Somma S, Mebazaa A, Harjola VP, CardShock study investigators. Current real-life use of vasopressors and inotropes in cardiogenic shock - adrenaline use is associated with excess organ injury and mortality. Crit Care. 2016;20:208–19.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Nieminen MS, Buerke M, Cohen-Solál A, Costa S, Edes I, Erlikh A, Franco F, Gibson C, Gorjup V, Guarracino F, Gustafsson F, Harjola VP, Husebye T, Karason K, Katsytadze I, Kaul S, Kivikko M, Marenzi G, Masip J, Matskeplishvili S, Mebazaa A, Møller JE, Nessler J, Nessler B, Ntalianis A, Oliva F, Pichler-Cetin E, Põder P, Recio-Mayoral A, Rex S, Rokyta R, Strasser RH, Zima E, Pollesello P. The role of levosimendan in acute heart failure complicating acute coronary syndrome: a review and expert consensus opinion. Int J Cardiol. 2016;218:150–7.

    Article  PubMed  Google Scholar 

  3. Shen B, Leung YK, Kwok YC, Kwan HY, Wong CO, Chen ZY, Huang Y, Yao X. Epinephrine-induced Ca2+ influx in vascular endothelial cells is mediated by CNGA2 channels. J Mol Cell Cardiol. 2008;45:437–45.

    Article  CAS  PubMed  Google Scholar 

  4. Hade EM, Lu B. Bias associated with using the estimated propensity score as a regression covariate. Stat Med. 2014;33:74–87.

    Article  PubMed  Google Scholar 

  5. Harjola VP, Lassus J, Sionis A, Kober L, Tarvasmaki T, Spinar J, et al. Clinical picture and risk prediction of short-term mortality in cardiogenic shock. Eur J Heart Fail. 2015;17:501–9. doi:10.1002/ejhf.260.

    Article  PubMed  Google Scholar 

  6. Thiele H, Zeymer U, Neumann FJ, Ferenc M, Olbrich HG, Hausleiter J, et al. Intraaortic balloon support for myocardial infarction with cardiogenic shock. N Engl J Med. 2012;367:1287–96. doi:10.1056/NEJMoa1208410.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The AltShock group: Stefano Carugo, Diego Castini, Emanuele Catena, Manlio Cipriani, Elena Corrada, Maria Frigerio, Maria Pia Gagliardone, Andrea Garascia, Francesco Gentile, Antonio Mafrici, Filippo Milazzo, Marco Negrini, Federico Pappalardo, Claudio Russo, Michele Senni, Romano Giuseppe Seregni.

Authors’ contributions

NM, MS, AS, MB, and FO designed the paper, participated in drafting the manuscript, and have read and approved the final version.

Competing interests

The authors declare that they have no competing interests.

Author information

Authors and Affiliations

Authors

Consortia

Corresponding author

Correspondence to Nuccia Morici.

Additional information

See related research by Tarvasmäki et al. http://ccforum.biomedcentral.com/articles/10.1186/s13054-016-1387-1

Rights and permissions

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Morici, N., Stucchi, M., Sacco, A. et al. Vasopressors and inotropes in cardiogenic shock: is there room for “adrenaline resuscitation”?. Crit Care 20, 302 (2016). https://doi.org/10.1186/s13054-016-1459-2

Download citation

  • Published:

  • DOI: https://doi.org/10.1186/s13054-016-1459-2

Keywords