Enteral versus intravenous approach for the sedation of critically ill patients: A randomized and controlled trial 11 Medical and Health Sciences 1103 Clinical Sciences

Giovanni Mistraletti, Michele Umbrello, Silvia Salini, Paolo Cadringher, Paolo Formenti, Davide Chiumello, Cristina Villa, Riccarda Russo, Silvia Francesconi, Federico Valdambrini, Giacomo Bellani, Alessandra Palo, Francesca Riccardi, Enrica Ferretti, Maurilio Festa, Anna Maria Gado, Martina Taverna, Cristina Pinna, Alessandro Barbiero, Pier Alda FerrariGaetano Iapichino, Alberto Morabito, Martin Langer, Franco Valenza, Roberto Malacrida, Marco Rambaldi, Paolo Spanu, Stefania Anania, Elisa Andrighi, Alessandra Di Carlo, Federica Martinetti, Serena Barello, Andrea Noto, Gianfranco Capello, Bruno Sabatelli, Giovanni Brenna, Morena Astori, Pietro Placido, Luciano Gattinoni, Alessandro Protti, Francesca Pagan, Virna Berto, Paola Roselli, Giulio Ronzoni, Eduardo Beck, Maurizio Gaiotto, Danilo Radrizzani, Luca Ferla, Riccardo Giudici, Laura Merlini, Antonio Pesenti, Alessia La Bruna, Emanuele Rezoagli, Alberto Lucchini, Antonio Braschi, Thekla Niebel, Marina Selvini, Sergio Cortesi, Attilio Quaini, Giorgio Iotti, Enrico Contri, Antonella Sacchi, Sergio Livigni, Giuseppe Naretto, Alessandro Deprado, Virna Venturi Degli Esposti, Pietro Caironi, Giulio Radeschi, Lorenzo Odetto, Daniele Ferrero, Stefano Cognolato, Roberto Penso, Roberta Vacchelli, Silvano Cardellino, Edda Bosco, Anna Bresciani, Ivana Pozzo, Annachiara Alessio, Vanessa Clarindo Rodrigues, Edna Biase, Nicoletta Vivaldi, Antonella Nava, Francesco Ponzetta, Lucilla Bavutti, Paola Martina, Beatriz Palacios, Giancarla Bergonzini

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: ICU patients must be kept conscious, calm, and cooperative even during the critical phases of illness. Enteral administration of sedative drugs might avoid over sedation, and would be as adequate as intravenous administration in patients who are awake, with fewer side effects and lower costs. This study compares two sedation strategies, for early achievement and maintenance of the target light sedation. Methods: This was a multicenter, single-blind, randomized and controlled trial carried out in 12 Italian ICUs, involving patients with expected mechanical ventilation duration > 72 h at ICU admission and predicted mortality > 12% (Simplified Acute Physiology Score II > 32 points) during the first 24 h on ICU. Patients were randomly assigned to receive intravenous (midazolam, propofol) or enteral (hydroxyzine, lorazepam, and melatonin) sedation. The primary outcome was percentage of work shifts with the patient having an observed Richmond Agitation-Sedation Scale (RASS) = target RASS ±1. Secondary outcomes were feasibility, delirium-free and coma-free days, costs of drugs, length of ICU and hospital stay, and ICU, hospital, and one-year mortality. Results: There were 348 patients enrolled. There were no differences in the primary outcome: enteral 89.8% (74.1-100), intravenous 94.4% (78-100), p = 0.20. Enteral-treated patients had more protocol violations: n = 81 (46.6%) vs 7 (4.2%), p < 0.01; more self-extubations: n = 14 (8.1%) vs 4 (2.4%), p = 0.03; a lighter sedative target (RASS = 0): 93% (71-100) vs 83% (61-100), p < 0.01; and lower total drug costs: 2.39 (0.75-9.78) vs 4.15 (1.20-20.19) €/day with mechanical ventilation (p = 0.01). Conclusions: Although enteral sedation of critically ill patients is cheaper and permits a lighter sedation target, it is not superior to intravenous sedation for reaching the RASS target. Trial registration: ClinicalTrials.gov, NCT01360346. Registered on 25 March 2011.

Original languageEnglish
Article number3
JournalCritical Care
Volume23
Issue number1
DOIs
Publication statusPublished - Jan 7 2019

Fingerprint

Critical Illness
Small Intestine
Randomized Controlled Trials
Health
Drug Costs
Hypnotics and Sedatives
Artificial Respiration
Length of Stay
Hydroxyzine
Lorazepam
Mortality
Delirium
Midazolam
Propofol
Melatonin
Coma
Intravenous Administration
Maintenance
Light
Costs and Cost Analysis

Keywords

  • Hydroxyzine
  • Hypnotics and sedatives
  • Melatonin
  • Nursing education research
  • Patient care planning

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Enteral versus intravenous approach for the sedation of critically ill patients : A randomized and controlled trial 11 Medical and Health Sciences 1103 Clinical Sciences. / Mistraletti, Giovanni; Umbrello, Michele; Salini, Silvia; Cadringher, Paolo; Formenti, Paolo; Chiumello, Davide; Villa, Cristina; Russo, Riccarda; Francesconi, Silvia; Valdambrini, Federico; Bellani, Giacomo; Palo, Alessandra; Riccardi, Francesca; Ferretti, Enrica; Festa, Maurilio; Gado, Anna Maria; Taverna, Martina; Pinna, Cristina; Barbiero, Alessandro; Ferrari, Pier Alda; Iapichino, Gaetano; Morabito, Alberto; Langer, Martin; Valenza, Franco; Malacrida, Roberto; Rambaldi, Marco; Spanu, Paolo; Anania, Stefania; Andrighi, Elisa; Di Carlo, Alessandra; Martinetti, Federica; Barello, Serena; Noto, Andrea; Capello, Gianfranco; Sabatelli, Bruno; Brenna, Giovanni; Astori, Morena; Placido, Pietro; Gattinoni, Luciano; Protti, Alessandro; Pagan, Francesca; Berto, Virna; Roselli, Paola; Ronzoni, Giulio; Beck, Eduardo; Gaiotto, Maurizio; Radrizzani, Danilo; Ferla, Luca; Giudici, Riccardo; Merlini, Laura; Pesenti, Antonio; La Bruna, Alessia; Rezoagli, Emanuele; Lucchini, Alberto; Braschi, Antonio; Niebel, Thekla; Selvini, Marina; Cortesi, Sergio; Quaini, Attilio; Iotti, Giorgio; Contri, Enrico; Sacchi, Antonella; Livigni, Sergio; Naretto, Giuseppe; Deprado, Alessandro; Venturi Degli Esposti, Virna; Caironi, Pietro; Radeschi, Giulio; Odetto, Lorenzo; Ferrero, Daniele; Cognolato, Stefano; Penso, Roberto; Vacchelli, Roberta; Cardellino, Silvano; Bosco, Edda; Bresciani, Anna; Pozzo, Ivana; Alessio, Annachiara; Clarindo Rodrigues, Vanessa; Biase, Edna; Vivaldi, Nicoletta; Nava, Antonella; Ponzetta, Francesco; Bavutti, Lucilla; Martina, Paola; Palacios, Beatriz; Bergonzini, Giancarla.

In: Critical Care, Vol. 23, No. 1, 3, 07.01.2019.

Research output: Contribution to journalArticle

Mistraletti, G, Umbrello, M, Salini, S, Cadringher, P, Formenti, P, Chiumello, D, Villa, C, Russo, R, Francesconi, S, Valdambrini, F, Bellani, G, Palo, A, Riccardi, F, Ferretti, E, Festa, M, Gado, AM, Taverna, M, Pinna, C, Barbiero, A, Ferrari, PA, Iapichino, G, Morabito, A, Langer, M, Valenza, F, Malacrida, R, Rambaldi, M, Spanu, P, Anania, S, Andrighi, E, Di Carlo, A, Martinetti, F, Barello, S, Noto, A, Capello, G, Sabatelli, B, Brenna, G, Astori, M, Placido, P, Gattinoni, L, Protti, A, Pagan, F, Berto, V, Roselli, P, Ronzoni, G, Beck, E, Gaiotto, M, Radrizzani, D, Ferla, L, Giudici, R, Merlini, L, Pesenti, A, La Bruna, A, Rezoagli, E, Lucchini, A, Braschi, A, Niebel, T, Selvini, M, Cortesi, S, Quaini, A, Iotti, G, Contri, E, Sacchi, A, Livigni, S, Naretto, G, Deprado, A, Venturi Degli Esposti, V, Caironi, P, Radeschi, G, Odetto, L, Ferrero, D, Cognolato, S, Penso, R, Vacchelli, R, Cardellino, S, Bosco, E, Bresciani, A, Pozzo, I, Alessio, A, Clarindo Rodrigues, V, Biase, E, Vivaldi, N, Nava, A, Ponzetta, F, Bavutti, L, Martina, P, Palacios, B & Bergonzini, G 2019, 'Enteral versus intravenous approach for the sedation of critically ill patients: A randomized and controlled trial 11 Medical and Health Sciences 1103 Clinical Sciences', Critical Care, vol. 23, no. 1, 3. https://doi.org/10.1186/s13054-018-2280-x
Mistraletti, Giovanni ; Umbrello, Michele ; Salini, Silvia ; Cadringher, Paolo ; Formenti, Paolo ; Chiumello, Davide ; Villa, Cristina ; Russo, Riccarda ; Francesconi, Silvia ; Valdambrini, Federico ; Bellani, Giacomo ; Palo, Alessandra ; Riccardi, Francesca ; Ferretti, Enrica ; Festa, Maurilio ; Gado, Anna Maria ; Taverna, Martina ; Pinna, Cristina ; Barbiero, Alessandro ; Ferrari, Pier Alda ; Iapichino, Gaetano ; Morabito, Alberto ; Langer, Martin ; Valenza, Franco ; Malacrida, Roberto ; Rambaldi, Marco ; Spanu, Paolo ; Anania, Stefania ; Andrighi, Elisa ; Di Carlo, Alessandra ; Martinetti, Federica ; Barello, Serena ; Noto, Andrea ; Capello, Gianfranco ; Sabatelli, Bruno ; Brenna, Giovanni ; Astori, Morena ; Placido, Pietro ; Gattinoni, Luciano ; Protti, Alessandro ; Pagan, Francesca ; Berto, Virna ; Roselli, Paola ; Ronzoni, Giulio ; Beck, Eduardo ; Gaiotto, Maurizio ; Radrizzani, Danilo ; Ferla, Luca ; Giudici, Riccardo ; Merlini, Laura ; Pesenti, Antonio ; La Bruna, Alessia ; Rezoagli, Emanuele ; Lucchini, Alberto ; Braschi, Antonio ; Niebel, Thekla ; Selvini, Marina ; Cortesi, Sergio ; Quaini, Attilio ; Iotti, Giorgio ; Contri, Enrico ; Sacchi, Antonella ; Livigni, Sergio ; Naretto, Giuseppe ; Deprado, Alessandro ; Venturi Degli Esposti, Virna ; Caironi, Pietro ; Radeschi, Giulio ; Odetto, Lorenzo ; Ferrero, Daniele ; Cognolato, Stefano ; Penso, Roberto ; Vacchelli, Roberta ; Cardellino, Silvano ; Bosco, Edda ; Bresciani, Anna ; Pozzo, Ivana ; Alessio, Annachiara ; Clarindo Rodrigues, Vanessa ; Biase, Edna ; Vivaldi, Nicoletta ; Nava, Antonella ; Ponzetta, Francesco ; Bavutti, Lucilla ; Martina, Paola ; Palacios, Beatriz ; Bergonzini, Giancarla. / Enteral versus intravenous approach for the sedation of critically ill patients : A randomized and controlled trial 11 Medical and Health Sciences 1103 Clinical Sciences. In: Critical Care. 2019 ; Vol. 23, No. 1.
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abstract = "Background: ICU patients must be kept conscious, calm, and cooperative even during the critical phases of illness. Enteral administration of sedative drugs might avoid over sedation, and would be as adequate as intravenous administration in patients who are awake, with fewer side effects and lower costs. This study compares two sedation strategies, for early achievement and maintenance of the target light sedation. Methods: This was a multicenter, single-blind, randomized and controlled trial carried out in 12 Italian ICUs, involving patients with expected mechanical ventilation duration > 72 h at ICU admission and predicted mortality > 12{\%} (Simplified Acute Physiology Score II > 32 points) during the first 24 h on ICU. Patients were randomly assigned to receive intravenous (midazolam, propofol) or enteral (hydroxyzine, lorazepam, and melatonin) sedation. The primary outcome was percentage of work shifts with the patient having an observed Richmond Agitation-Sedation Scale (RASS) = target RASS ±1. Secondary outcomes were feasibility, delirium-free and coma-free days, costs of drugs, length of ICU and hospital stay, and ICU, hospital, and one-year mortality. Results: There were 348 patients enrolled. There were no differences in the primary outcome: enteral 89.8{\%} (74.1-100), intravenous 94.4{\%} (78-100), p = 0.20. Enteral-treated patients had more protocol violations: n = 81 (46.6{\%}) vs 7 (4.2{\%}), p < 0.01; more self-extubations: n = 14 (8.1{\%}) vs 4 (2.4{\%}), p = 0.03; a lighter sedative target (RASS = 0): 93{\%} (71-100) vs 83{\%} (61-100), p < 0.01; and lower total drug costs: 2.39 (0.75-9.78) vs 4.15 (1.20-20.19) €/day with mechanical ventilation (p = 0.01). Conclusions: Although enteral sedation of critically ill patients is cheaper and permits a lighter sedation target, it is not superior to intravenous sedation for reaching the RASS target. Trial registration: ClinicalTrials.gov, NCT01360346. Registered on 25 March 2011.",
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author = "Giovanni Mistraletti and Michele Umbrello and Silvia Salini and Paolo Cadringher and Paolo Formenti and Davide Chiumello and Cristina Villa and Riccarda Russo and Silvia Francesconi and Federico Valdambrini and Giacomo Bellani and Alessandra Palo and Francesca Riccardi and Enrica Ferretti and Maurilio Festa and Gado, {Anna Maria} and Martina Taverna and Cristina Pinna and Alessandro Barbiero and Ferrari, {Pier Alda} and Gaetano Iapichino and Alberto Morabito and Martin Langer and Franco Valenza and Roberto Malacrida and Marco Rambaldi and Paolo Spanu and Stefania Anania and Elisa Andrighi and {Di Carlo}, Alessandra and Federica Martinetti and Serena Barello and Andrea Noto and Gianfranco Capello and Bruno Sabatelli and Giovanni Brenna and Morena Astori and Pietro Placido and Luciano Gattinoni and Alessandro Protti and Francesca Pagan and Virna Berto and Paola Roselli and Giulio Ronzoni and Eduardo Beck and Maurizio Gaiotto and Danilo Radrizzani and Luca Ferla and Riccardo Giudici and Laura Merlini and Antonio Pesenti and {La Bruna}, Alessia and Emanuele Rezoagli and Alberto Lucchini and Antonio Braschi and Thekla Niebel and Marina Selvini and Sergio Cortesi and Attilio Quaini and Giorgio Iotti and Enrico Contri and Antonella Sacchi and Sergio Livigni and Giuseppe Naretto and Alessandro Deprado and {Venturi Degli Esposti}, Virna and Pietro Caironi and Giulio Radeschi and Lorenzo Odetto and Daniele Ferrero and Stefano Cognolato and Roberto Penso and Roberta Vacchelli and Silvano Cardellino and Edda Bosco and Anna Bresciani and Ivana Pozzo and Annachiara Alessio and {Clarindo Rodrigues}, Vanessa and Edna Biase and Nicoletta Vivaldi and Antonella Nava and Francesco Ponzetta and Lucilla Bavutti and Paola Martina and Beatriz Palacios and Giancarla Bergonzini",
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month = "1",
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TY - JOUR

T1 - Enteral versus intravenous approach for the sedation of critically ill patients

T2 - A randomized and controlled trial 11 Medical and Health Sciences 1103 Clinical Sciences

AU - Mistraletti, Giovanni

AU - Umbrello, Michele

AU - Salini, Silvia

AU - Cadringher, Paolo

AU - Formenti, Paolo

AU - Chiumello, Davide

AU - Villa, Cristina

AU - Russo, Riccarda

AU - Francesconi, Silvia

AU - Valdambrini, Federico

AU - Bellani, Giacomo

AU - Palo, Alessandra

AU - Riccardi, Francesca

AU - Ferretti, Enrica

AU - Festa, Maurilio

AU - Gado, Anna Maria

AU - Taverna, Martina

AU - Pinna, Cristina

AU - Barbiero, Alessandro

AU - Ferrari, Pier Alda

AU - Iapichino, Gaetano

AU - Morabito, Alberto

AU - Langer, Martin

AU - Valenza, Franco

AU - Malacrida, Roberto

AU - Rambaldi, Marco

AU - Spanu, Paolo

AU - Anania, Stefania

AU - Andrighi, Elisa

AU - Di Carlo, Alessandra

AU - Martinetti, Federica

AU - Barello, Serena

AU - Noto, Andrea

AU - Capello, Gianfranco

AU - Sabatelli, Bruno

AU - Brenna, Giovanni

AU - Astori, Morena

AU - Placido, Pietro

AU - Gattinoni, Luciano

AU - Protti, Alessandro

AU - Pagan, Francesca

AU - Berto, Virna

AU - Roselli, Paola

AU - Ronzoni, Giulio

AU - Beck, Eduardo

AU - Gaiotto, Maurizio

AU - Radrizzani, Danilo

AU - Ferla, Luca

AU - Giudici, Riccardo

AU - Merlini, Laura

AU - Pesenti, Antonio

AU - La Bruna, Alessia

AU - Rezoagli, Emanuele

AU - Lucchini, Alberto

AU - Braschi, Antonio

AU - Niebel, Thekla

AU - Selvini, Marina

AU - Cortesi, Sergio

AU - Quaini, Attilio

AU - Iotti, Giorgio

AU - Contri, Enrico

AU - Sacchi, Antonella

AU - Livigni, Sergio

AU - Naretto, Giuseppe

AU - Deprado, Alessandro

AU - Venturi Degli Esposti, Virna

AU - Caironi, Pietro

AU - Radeschi, Giulio

AU - Odetto, Lorenzo

AU - Ferrero, Daniele

AU - Cognolato, Stefano

AU - Penso, Roberto

AU - Vacchelli, Roberta

AU - Cardellino, Silvano

AU - Bosco, Edda

AU - Bresciani, Anna

AU - Pozzo, Ivana

AU - Alessio, Annachiara

AU - Clarindo Rodrigues, Vanessa

AU - Biase, Edna

AU - Vivaldi, Nicoletta

AU - Nava, Antonella

AU - Ponzetta, Francesco

AU - Bavutti, Lucilla

AU - Martina, Paola

AU - Palacios, Beatriz

AU - Bergonzini, Giancarla

PY - 2019/1/7

Y1 - 2019/1/7

N2 - Background: ICU patients must be kept conscious, calm, and cooperative even during the critical phases of illness. Enteral administration of sedative drugs might avoid over sedation, and would be as adequate as intravenous administration in patients who are awake, with fewer side effects and lower costs. This study compares two sedation strategies, for early achievement and maintenance of the target light sedation. Methods: This was a multicenter, single-blind, randomized and controlled trial carried out in 12 Italian ICUs, involving patients with expected mechanical ventilation duration > 72 h at ICU admission and predicted mortality > 12% (Simplified Acute Physiology Score II > 32 points) during the first 24 h on ICU. Patients were randomly assigned to receive intravenous (midazolam, propofol) or enteral (hydroxyzine, lorazepam, and melatonin) sedation. The primary outcome was percentage of work shifts with the patient having an observed Richmond Agitation-Sedation Scale (RASS) = target RASS ±1. Secondary outcomes were feasibility, delirium-free and coma-free days, costs of drugs, length of ICU and hospital stay, and ICU, hospital, and one-year mortality. Results: There were 348 patients enrolled. There were no differences in the primary outcome: enteral 89.8% (74.1-100), intravenous 94.4% (78-100), p = 0.20. Enteral-treated patients had more protocol violations: n = 81 (46.6%) vs 7 (4.2%), p < 0.01; more self-extubations: n = 14 (8.1%) vs 4 (2.4%), p = 0.03; a lighter sedative target (RASS = 0): 93% (71-100) vs 83% (61-100), p < 0.01; and lower total drug costs: 2.39 (0.75-9.78) vs 4.15 (1.20-20.19) €/day with mechanical ventilation (p = 0.01). Conclusions: Although enteral sedation of critically ill patients is cheaper and permits a lighter sedation target, it is not superior to intravenous sedation for reaching the RASS target. Trial registration: ClinicalTrials.gov, NCT01360346. Registered on 25 March 2011.

AB - Background: ICU patients must be kept conscious, calm, and cooperative even during the critical phases of illness. Enteral administration of sedative drugs might avoid over sedation, and would be as adequate as intravenous administration in patients who are awake, with fewer side effects and lower costs. This study compares two sedation strategies, for early achievement and maintenance of the target light sedation. Methods: This was a multicenter, single-blind, randomized and controlled trial carried out in 12 Italian ICUs, involving patients with expected mechanical ventilation duration > 72 h at ICU admission and predicted mortality > 12% (Simplified Acute Physiology Score II > 32 points) during the first 24 h on ICU. Patients were randomly assigned to receive intravenous (midazolam, propofol) or enteral (hydroxyzine, lorazepam, and melatonin) sedation. The primary outcome was percentage of work shifts with the patient having an observed Richmond Agitation-Sedation Scale (RASS) = target RASS ±1. Secondary outcomes were feasibility, delirium-free and coma-free days, costs of drugs, length of ICU and hospital stay, and ICU, hospital, and one-year mortality. Results: There were 348 patients enrolled. There were no differences in the primary outcome: enteral 89.8% (74.1-100), intravenous 94.4% (78-100), p = 0.20. Enteral-treated patients had more protocol violations: n = 81 (46.6%) vs 7 (4.2%), p < 0.01; more self-extubations: n = 14 (8.1%) vs 4 (2.4%), p = 0.03; a lighter sedative target (RASS = 0): 93% (71-100) vs 83% (61-100), p < 0.01; and lower total drug costs: 2.39 (0.75-9.78) vs 4.15 (1.20-20.19) €/day with mechanical ventilation (p = 0.01). Conclusions: Although enteral sedation of critically ill patients is cheaper and permits a lighter sedation target, it is not superior to intravenous sedation for reaching the RASS target. Trial registration: ClinicalTrials.gov, NCT01360346. Registered on 25 March 2011.

KW - Hydroxyzine

KW - Hypnotics and sedatives

KW - Melatonin

KW - Nursing education research

KW - Patient care planning

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U2 - 10.1186/s13054-018-2280-x

DO - 10.1186/s13054-018-2280-x

M3 - Article

C2 - 30616675

AN - SCOPUS:85059677436

VL - 23

JO - Critical Care

JF - Critical Care

SN - 1466-609X

IS - 1

M1 - 3

ER -