The effect of dexmedetomidine on vasopressor requirements in patients with septic shock: a subgroup analysis of the Sedation Practice in Intensive Care Evaluation [SPICE III] Trial

Abstract

Background: Septic shock is associated with decreased vasopressor responsiveness. Experimental data suggest that central alpha2-agonists like dexmedetomidine (DEX) increase vasopressor responsiveness and reduce catecholamine requirements in septic shock. However, DEX may also cause hypotension and bradycardia. Thus, it remains unclear whether DEX is hemodynamically safe or helpful in this setting. Methods: In this post hoc subgroup analysis of the Sedation Practice in Intensive Care Evaluation (SPICE III) trial, an international randomized trial comparing early sedation with dexmedetomidine to usual care in critically patients receiving mechanical ventilation, we studied patients with septic shock admitted to two tertiary ICUs in Australia and Switzerland. The primary outcome was vasopressor requirements in the first 48 h after randomization, expressed as noradrenaline equivalent dose (NEq [μg/kg/min] = noradrenaline + adrenaline + vasopressin/0.4). Results: Between November 2013 and February 2018, 417 patients were recruited into the SPICE III trial at both sites. Eighty-three patients with septic shock were included in this subgroup analysis. Of these, 44 (53%) received DEX and 39 (47%) usual care. Vasopressor requirements in the first 48 h were similar between the two groups. Median NEq dose was 0.03 [0.01, 0.07] μg/kg/min in the DEX group and 0.04 [0.01, 0.16] μg/kg/min in the usual care group (p = 0.17). However, patients in the DEX group had a lower NEq/MAP ratio, indicating lower vasopressor requirements to maintain the target MAP. Moreover, on adjusted multivariable analysis, higher dexmedetomidine dose was associated with a lower NEq/MAP ratio.

The autonomic nervous system in septic shock and its role as a future therapeutic target: a narrative review

“…This hypothesis also suggests that the more the α1-receptors are desensitized by high concentrations of endogenous catecholamines (e.g., in refractory septic shock), the larger the expected improved responsiveness to vasopressors. In recent studies and subgroup analyses, dexmedetomidine appeared to be associated with lower vasopressor requirements to maintain the same MAP target in septic shock [ 101 , 102 ].…”

Emerging benefits and drawbacks of α2‐adrenoceptor agonists in the management of sepsis and critical illness

“…In this regard, a recent post hoc subgroup analysis of patients with septic shock ( N = 83) included in the SPICE III trial reported similar vasopressor requirements in the first 48 h in patients. However, on multivariable adjusted analysis (for admission diagnosis, baseline noradrenaline equivalents/MAP ratio, continuous renal replacement therapy, age, hydrocortisone treatment, and liver cirrhosis), vasopressor requirements to maintain target MAP were significantly lower in the dexmedetomidine than in the usual care group (ratio of difference in geometric means 1.44 [1.07, 1.95]) (Cioccari et al, 2020).…”

Optimal Sedation and Pain Management: A Patient- and Symptom-Oriented Paradigm

“…It has sedative, anxiolytic, and analgesic properties with minimal respiratory depression. 75 While the main side effects of dexmedetomidine are hypotension and bradycardia in vasopressor dependent patients, it is well tolerated and shown to reduce vasopressor requirements in septic patients 33,76 and improve outcomes after cardiac surgery. 77 The commonest use of dexmedetomidine in clinical practice is in the management of delirium and agitation.…”