Cvetkovic, Mirjana

Inwald, David P

Lutman, Daniel H

Pathan, Nazima

Peters, Mark J

Ramnarayan, Padmanabhan

Ray, Samiran

Critical Care

English

PubMed

Ray, S

Cvetkovic, M

Lutman, DH

Pathan, N

Ramnarayan, P

Inwald, DP

Peters, MJ

Spiral - Imperial College Digital Repository

LETTER Open AccessReal-life use of vasopressors and inotropesin cardiogenic shock—observation isnecessarily ‘theory-laden’Samiran Ray1,5* , Mirjana Cvetkovic2, Daniel H. Lutman1, Nazima Pathan3, Padmanabhan Ramnarayan1,4,David P. Inwald4 and Mark J. Peters1,5See related Research by Tarvasmäki et al., https://ccforum.biomedcentral.com/articles/10.1186/s13054-016-1387-1We commend the attempt of Tarvasmäki et al. [1] toidentify the mortality risk associated with individualvaso-active agents used in cardiogenic shock. However,despite their rigorous statistical analysis, we recom-mend caution in interpreting these results. Propensityscore matching accounts for prior bias in the choice ofvaso-active agents, but this choice of agent is oftendeeply engrained in individual clinician dogma whicheven propensity score matching may not uncover.We recently conducted a similar retrospective ana-lysis of vaso-active agents used in children with sepsisduring stabilisation and transport of children by ourpaediatric intensive care transport service. Cold shockis common in sepsis in children, and the choice ofvaso-active agent depends on the balance of inotropyor vasoconstriction needed. During transport, haemo-dynamic assessment is limited—choices of vaso-activeagent used are made on limited data. Over a 7-yearperiod (2005–2011), 364/633 (57.5 %) children werestarted at least on one vaso-active agent prior tointensive care unit admission. Epinephrine was associ-ated with a crude mortality of 3.84 (95 % CI 2.5–5.91) compared to 1.8 (95 % CI 1.17–2.76) and 1.39(95 % CI 0.91–2.1) for norepinephrine and dopamine,respectively. However, when standardised for riskusing the PIM (Paediatric Index of Mortality) score,the standardised mortality ratio for epinephrine was1.30 (95 % CI 0.98–1.63). When propensity scorematching was used to account for choice of agent(calculated using age, weight, fluids administered,need for prior CPR, other agent use), no differencewas seen between those who did and did not receiveepinephrine (p value = 0.09). Yet Ventura et al. dem-onstrated, via a randomised controlled trial, thatdopamine was associated with an increased mortalityin children with sepsis compared to the use of epi-nephrine (OR 6.5, 95 % CI 1.1–37.8) [2]!These contradictory findings are likely be a reflec-tion of how different drugs are used—as the degreeof statistical adjustment for confounding was im-proved (from crude to standardised mortality topropensity score matching), the initial mortality asso-ciation with epinephrine use disappeared. When theuse of drugs was protocolised in randomised con-trolled trial circumstances the association was re-versed, with epinephrine showing a mortality benefitover dopamine. It is likely that more important thanthe choice of drug may be the use of the rightamount of the right drug at the right time [3]. Wejoin the authors to call for further randomised con-trolled trials to determine an evidence-based approachto vaso-active agent use.* Correspondence: samiran.ray@gosh.nhs.uk1Children’s Acute Transport Service, Great Ormond Street Hospital NHS Trust,London WC1N 3JH, UK5University College London Institute of Child Health, 30 Guildford Street,London, UKFull list of author information is available at the end of the article© 2016 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, andreproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link tothe 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.Ray et al. Critical Care  (2016) 20:293 DOI 10.1186/s13054-016-1473-4Additional fileAdditional file 1: Contingency table with data used to calculate crudeodd ratios of death for each vasoactive agent. (XLSX 11 kb)AbbreviationsOR: Odds ratio; CI: Confidence intervalAcknowledgementsThe authors would like to thank Ms Marissa Willock, Clinical Administrator,Children’s Acute Transport Service, for her assistance with data collection.FundingThis work was undertaken at Great Ormond Street Hospital/UCL Institute ofChild Health, which received a proportion of funding from the Departmentof Health’s NIHR Biomedical Research Centre’s funding scheme.Availability of data and materialsContingency tables provided as Additional file 1.Authors’ contributionsThe study was part of a wider project exploring the outcomes from sepsis ina transport service cohort. The study was conceived by MJP, PR, DI, DHL, andNP; data were collected by SR and MC; data were verified by SR and MJP;data were analysed by SR; the manuscript was written by SR, with reviewand comments from PR, DI, NP, MJP. All authors read and approved the finalmanuscript.Authors’ informationAs title page.Competing interestsThe authors declare that they have no competing interests.Ethics approval and consent to participateThe study was registered with the Institutional Audit Department (Project ref.1014) as a wider service evaluation of the management of sepsis. It wasdiscussed with the Bloomsbury Research Ethics Committee who waived arequirement for formal review.Author details1Children’s Acute Transport Service, Great Ormond Street Hospital NHS Trust,London WC1N 3JH, UK. 2University Hospitals of Leicester NHS Trusts,Leicester, UK. 3Addenbrookes Hospital, Cambridge University Hospitals NHSTrust, Cambridge, UK. 4Imperial College Healthcare NHS Trust, London, UK.5University College London Institute of Child Health, 30 Guildford Street,London, UK.References1. 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-lifeuse of vasopressors and inotropes in cardiogenic shock—adrenaline useis associated with excess organ injury and mortality. Crit Care. 2016;20(1):208.2. Ventura AM, Shieh HH, Bousso A, Góes PF, de Cássia FO, Fernandes I, de SouzaDC, Paulo RL, Chagas F, Gilio AE. Double-blind prospective randomizedcontrolled trial of dopamine versus epinephrine as first-line vasoactive drugs inpediatric septic shock. Crit Care Med. 2015;43(11):2292–302.3. Rachoin JS, Dellinger RP. Timing of norepinephrine in septic patients: NOTtoo little too late. Crit Care. 2014;18(6):691.Ray et al. Critical Care  (2016) 20:293 Page 2 of 2

Real-life use of vasopressors and inotropes in cardiogenic shock-observation is necessarily 'theory-laden'

Samiran Ray

Mirjana Cvetkovic

Daniel H. Lutman

Nazima Pathan

Padmanabhan Ramnarayan

David P. Inwald

Mark J. Peters

Springer - Publisher Connector

Real-life use of vasopressors and inotropes in cardiogenic shock—observation is necessarily ‘theory-laden’

Apollo (Cambridge)

Real-life use of vasopressors and inotropes in cardiogenic shock-observation is necessarily 'theory-laden'.

UCL Discovery

Crossref

http://dx.doi.org/10.1186/s13054-016-1473-4

Real-life use of vasopressors and inotropes in cardiogenic shock-observation is necessarily 'theory-laden'.

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Spiral - Imperial College Digital Repository

Springer - Publisher Connector

Apollo (Cambridge)

UCL Discovery

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