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) 

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Given that all routinely used catecholamines target the same adrenergic receptors, most clinicians are inclined to add a non-catecholamine vasopressor to treat patients with refractory hypotension due to septic shock, a decision based on three key factors: availability (a relatively rigid constraint), familiarity (often governed by previous practice), and safety profile. In our opinion, further consideration should be potential vasopressor response. Following appropriate volume resuscitation, the response to different vasopressor classes is neither uniform nor predictable. Furthermore, the responsiveness to a vasopressor may impact the outcome. Indeed, norepinephrine, recognized as the first-line vasopressor, often demonstrates a variable response which may be due to various factors which include pre-existing therapy/medications, genetics, the underlying pathophysiology of septic shock, and/or receptor responsiveness.[7–10] Both human and pre-clinical data demonstrate that septic shock impairs sympathetic modulation of the heart and vasculature.[7] In fact, septic shock patients who maintain adrenergic responsiveness have better outcomes.[9] Similarly, non-catecholamine vasopressors including vasopressin and angiotensin II can be affected by concomitant medications, genetics, and altered receptor responsiveness as a consequence of inflammation and sepsis.[10–12] The net effects of all of these parameters are difficult to compute at the bedside, but the key issue is whether responsiveness to a vasopressor impacts outcomes.

Non-responders to high-dose catecholamines have a dismal outcome.[13] In terms of non-catecholamine agents, less than 50% of patients demonstrate a MAP response to low-dose vasopressin with this group having a significantly better survival than those that fail to respond[14] (Table 1). Similarly, approximately 70% of patients who receive angiotensin II have a MAP response.[6,15] In a responder analysis, the ATHOS-3 study showed that a responder's chance of survival is significantly better than that of patients who fail to respond to angiotensin II[6,15] (Table 1, Figure 1). It follows that in patients with septic shock, the choice of vasopressor should be governed by the patient's likelihood of responding and the sensitivity to treatment. This notion is in keeping with current antimicrobial therapy paradigm wherein clinicians obtain cultures and start broad-spectrum antibiotics with the intention of de-escalating the antibiotics once the causative organism is identified.

Figure 1.

Survival probability by MAP response at hour 3 for patients in the ATHOS-3 trial