TY - JOUR
T1 - The Effect of Propofol and Dexmedetomidine Sedation on Norepinephrine Requirements in Septic Shock Patients
T2 - A Crossover Trial
AU - Morelli, Andrea
AU - Sanfilippo, Filippo
AU - Arnemann, Philip
AU - Hessler, Michael
AU - Kampmeier, Tim G
AU - D'Egidio, Annalia
AU - Orecchioni, Alessandra
AU - Santonocito, Cristina
AU - Frati, Giacomo
AU - Greco, Ernesto
AU - Westphal, Martin
AU - Rehberg, Sebastian W
AU - Ertmer, Christian
PY - 2019/2
Y1 - 2019/2
N2 - 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.
AB - 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.
KW - Acid-Base Equilibrium/drug effects
KW - Adrenergic alpha-Agonists/administration & dosage
KW - Cross-Over Studies
KW - Deep Sedation/methods
KW - Dexmedetomidine/therapeutic use
KW - Female
KW - Hemodynamics/drug effects
KW - Humans
KW - Hypnotics and Sedatives/therapeutic use
KW - Male
KW - Middle Aged
KW - Norepinephrine/administration & dosage
KW - Propofol/therapeutic use
KW - Shock, Septic/drug therapy
U2 - 10.1097/CCM.0000000000003520
DO - 10.1097/CCM.0000000000003520
M3 - Article
VL - 47
SP - e89-e95
JO - Critical Care Medicine
JF - Critical Care Medicine
SN - 0090-3493
IS - 2
ER -