Broad Spectrum Vasopressors
A New Approach to the Initial Management of Septic Shock?
Lakhmir S. Chawla; Marlies Ostermann; Lui Forni; George F. Tidmarsh
Crit Care. 2019;23(124)
The mainstay of hemodynamic treatment of septic shock is fluid resuscitation followed by vasopressors where fluids alone are insufficient to achieve target blood pressure. Norepinephrine, a catecholamine, is the first-line vasopressor used worldwide but given that all routinely used catecholamines target the same adrenergic receptors, many clinicians may add a non-catecholamine vasopressor where refractory hypotension due to septic shock is present. However, the timing of this additional intervention is variable. This decision is based on three key factors: availability, familiarity, and safety profile. In our opinion, further consideration should be potential vasopressor response because following appropriate volume resuscitation, the response to different vasopressor classes is neither uniform nor predictable. Critically ill patients who are non-responders to high-dose catecholamines have a dismal outcome. Similarly, patients have a variable response to non-catecholamine agents including vasopressin and angiotensin II: but where patients exhibit a blood pressure response the outcomes are improved over non-responders. This variable responsiveness to vasopressors is similar to the clinical approach of anti-microbial sensitivity. In this commentary, the authors propose the concept of "broad spectrum vasopressors" wherein patients with septic shock are started on multiple vasopressors with a different mechanism of action simultaneously while the vasopressor sensitivity is assessed. Once the vasopressor sensitivities are assessed, then the vasopressors are 'de-escalated' accordingly. We believe that this concept may offer a new approach to the treatment of septic shock.
Crit Care. 2019;23(124) © 2019 BioMed Central, Ltd.
Copyright to this article is held by the author(s), licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original citation.
Table 1. Outcomes Assessed by MAP Response to Vasopressin or Angiotensin II
Vasopressin [14]
Angiotensin II [6]
Responder 45% (n = 426)
Non-responder 55% (n = 512)
Responder 69.9% (n = 114)
Non-responder 30.1% (n = 49)
In-patient mortality (%) 56.6% 71.7% < 0.001 35% 71% < 0.0001
Catecholamine dose (mcg/kg/min) 0.35 ± 0.25 0.33 ± 0.27 0.18 0.32 ± 0.32 0.53 ± 0.39 0.0002
MAP (mmHg) 69 ± 12 65 ± 12 < 0.001 67.1 ± 5.21 64.8 ± 5.02 0.0087
Steroids (%) 58.9 62.5 0.26 55.3 57.1 0.8647
Lactate (mmol/L) 4.0 ± 3.6 5.4 ± 4.8 < 0.001 3.43 ± 2.43 5.80 ± 6.01 0.013
SOFA score 13 ± 4 12 ± 3 0.49 11.65 ± 2.78 12.06 ± 2.99 0.4313
Age, years 62 ± 14 61 ± 15 0.17 61.7 ± 15.32 63.1 ± 16.33 0.4278
Lakhmir S. Chawla1,2*, Marlies Ostermann3, Lui Forni4,5 and George F. Tidmarsh2,6
1Veterans Affairs Medical Center, 3350 La Jolla Village Dr, San Diego, CA 92161, USA. 2La Jolla Pharmaceutical Company, San Diego, CA, USA. 3King's College London, Guy's & St Thomas' Hospital, London, UK. 4Department of Clinical and Experimental Medicine, Faculty of Health Sciences, University of Surrey, Guildford, UK. 5Intensive Care Unit, Royal Surrey County Hospital NHS Foundation Trust, Guildford, UK. 6Stanford University School of Medicine, Palo Alto, CA 94305, USA.
* Correspondence
minkchawla@gmail.com
LSC, MO, LJ, and GFT were involved in the concept development, data interpretation/analysis, and development of the commentary. All authors contributed in writing the manuscript and approved the final manuscript.
LSC and GFT are both employees and stockholders of La Jolla Pharmaceutical Company. The other authors declare that they have no competing interests.
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