Andrea Morelli1, Filippo Sanfilippo2, Philip Arnemann3, Michael Hessler3, Tim G Kampmeier3, Annalia D'Egidio1, Alessandra Orecchioni1, Cristina Santonocito2, Giacomo Frati4,5, Ernesto Greco1, Martin Westphal3, Sebastian W Rehberg6, Christian Ertmer3. 1. Department of Cardiovascular, Respiratory, Nephrological, Anesthesiological and Geriatric Sciences, University of Rome, "La Sapienza," Policlinico Umberto Primo, Viale del Policlinico, Rome, Italy. 2. Department of Anesthesia and Intensive Care, IRCCS-ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), Via Ernesto Tricomi, Palermo, Italy. 3. Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital of Muenster, Albert-Schweitzer-Campus, Muenster, Germany. 4. Department of Medico-Surgical Sciences and Biotechnologies, University of Rome "La Sapienza," Corso della Repubblica, Latina, Italy. 5. Department of AngioCardioNeurology, IRCCS Neuromed, Via Atinense, Pozzilli, Italy. 6. Department of Anesthesiology, Intensive Care, Emergency Medicine, Transfusion Medicine and Pain Therapy, Protestant Hospital of the Bethel Foundation, Burgsteig, Bielefeld, Germany.
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 requiringnorepinephrine 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.
RCT Entities:
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 shockpatients 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 shockpatients.
Authors: Joseph Sinnott; Christopher V Holthaus; Enyo Ablordeppey; Brian T Wessman; Brian W Roberts; Brian M Fuller Journal: West J Emerg Med Date: 2021-08-22
Authors: Angelina Grest; Judith Kurmann; Markus Müller; Victor Jeger; Bernard Krüger; Donat R Spahn; Dominique Bettex; Alain Rudiger Journal: Crit Care Res Pract Date: 2020-05-07
Authors: D Longrois; F Petitjeans; O Simonet; M de Kock; M Belliveau; C Pichot; Th Lieutaud; M Ghignone; L Quintin Journal: Rom J Anaesth Intensive Care Date: 2021-01-04
Authors: Dan Longrois; Fabrice Petitjeans; Olivier Simonet; Marc de Kock; Marc Belliveau; Cyrille Pichot; Thomas Lieutaud; Marco Ghignone; Luc Quintin Journal: Rev Bras Ter Intensiva Date: 2022-01-24
Authors: Charles A Flanders; Alistair S Rocke; Stuart A Edwardson; J Kenneth Baillie; Timothy S Walsh Journal: Crit Care Date: 2019-12-11 Impact factor: 9.097
Authors: Halvor Langeland; Daniel Bergum; Magnus Løberg; Knut Bjørnstad; Thomas R Skaug; Trond Nordseth; Pål Klepstad; Nils Kristian Skjærvold Journal: Open Heart Date: 2022-01