The Effect of Propofol and Dexmedetomidine Sedation on Norepinephrine Requirements in Septic Shock Patients: A Crossover Trial

Abstract

Objectives: Propofol-based sedation may increase hemodynamic instability by decreasing vascular tone and venous return. Incremental exogenous catecholamines doses may be required to counteract such effects, aggravating the deleterious effects of sympathetic overstimulation. α-2 adrenergic agonists have been reported to decrease norepinephrine requirements in experimental septic shock. The aim of the present study is to test the hypothesis that switching from sedation with propofol to the α-2 agonist dexmedetomidine may decrease norepinephrine doses in septic shock. Design: Prospective open-label crossover study. Settings: University hospital, ICU. Patients: Thirty-eight septic shock patients requiring norepinephrine to maintain adequate mean arterial pressure and needing deep sedation with propofol and remifentanil to maintain a Richmond Agitation-Sedation Scale score between –3 and –4. Interventions: An initial set of measurements including hemodynamics, norepinephrine doses, and depth of sedation were obtained during sedation with propofol. Propofol was then replaced by dexmedetomidine and a second set of data was obtained after 4 hours of dexmedetomidine infusion. Sedation was switched back to propofol, and a final set of measurements was obtained after 8 hours. A Richmond Agitation-Sedation Scale score between –3 and –4 was maintained during the study period. Measurements and Main Results: Norepinephrine requirements decreased from 0.69 ± 0.72 μg/kg/min before dexmedetomidine to 0.30 ± 0.25 μg/kg/min 4 hours after dexmedetomidine infusion, increasing again to 0.42 ± 0.36 μg/kg/min while on propofol 8 hours after stopping dexmedetomidine (p < 0.005). Dexmedetomidine dosage was 0.7 ± 0.2 μg/kg/hr. Before and after dexmedetomidine infusion, sedative doses remained unchanged (propofol 2.6 ± 1.2 vs 2.6 ± 1.2 mg/kg/hr; p = 0.23 and remifentanil 1.27 ± 0.17 vs 1.27 ± 0.16 μg/kg/hr; p = 0.52, respectively). Richmond Agitation-Sedation Scale was –4 (–4 to –3) before, –4 (–4 to –3) during, and –4 (–4 to –4) after dexmedetomidine (p = 0.07). Conclusions: For a comparable level of sedation, switching from propofol to dexmedetomidine resulted in a reduction of catecholamine requirements in septic shock patients.

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

“…As alpha-2 agonist, dexmedetomidine may increase the risk of hypotension and bradycardia [14,15] and, in patients with septic shock, this may be both dangerous and harmful. However, experimental data also suggest that dexmedetomidine can be administered in septic shock and may even have catecholamine-sparing effects [5,[16][17][18][19][20][21]. Our findings are consistent with such experimental observations.…”

Dexmedetomidine Improves Cardiovascular and Ventilatory Outcomes in Critically Ill Patients: Basic and Clinical Approaches

“…However, DEX seems promising in this context, and mechanistic, pharmacodynamic, and pharmacokinetic studies with DEX in critical septic patients have increased in recent years. Recent evidence in septic shock sedated patients have shown that for a comparable level of sedation, switching from propofol to dexmedetomidine resulted in a reduction of norepinephrine requirements in septic shock patients (Morelli et al, 2019). Table 3 shows the benefits of adding DEX in different clinical settings.…”

“…Potential neuroprotection in Ischemic brain injury Ren et al, 2016;Alam et al, 2017;Sottas, 2017;Schomer et al, 2019 Sepsis Anti-inflamatory effects in sepsis. Potential hemodynamic stability Xiang et al, 2014;Morelli et al, 2019 AUTHOR CONTRIBUTIONS RC: designed the manuscript and the structure of the themes and wrote about animal models and basic targets of DEX. MI and IC: wrote about human pharmacokinetics of DEX.…”

Dexmedetomidine reduces norepinephrine requirements and preserves renal oxygenation and function in ovine septic acute kidney injury

“…17,18 Currently, DEX is not recommended as a standard-of-care sedative due to its central action to inhibit sympathetic nerve activity, 19,20 which would be expected to reduce blood pressure in sepsis. However, in both clinical [21][22][23] and experimental 19,24,25 sepsis, there is evidence that treatment with a 2 -adrenergic receptor agonists improves responsiveness to exogenous vasopressors such as norepinephrine, phenylephrine, and angiotensin II, which likely accounts for their ability to preserve blood pressure. A multinational, doubleblinded, randomized clinical trial is currently assessing DEX as a primary sedative agent, 26 making this agent of clinical interest and relevance.…”