Restricted Polypharmacy Compared to Usual Care in Mechanically Ventilated Patients: A Retrospective Cohort Study.
Journal
Anesthesia and analgesia
ISSN: 1526-7598
Titre abrégé: Anesth Analg
Pays: United States
ID NLM: 1310650
Informations de publication
Date de publication:
01 06 2023
01 06 2023
Historique:
medline:
22
5
2023
pubmed:
5
4
2023
entrez:
4
4
2023
Statut:
ppublish
Résumé
Adverse effects of excessive sedation in critically ill mechanically ventilated patients are well described. Although guidelines strongly recommend minimizing sedative use, additional agents are added as infusions, often empirically. The tradeoffs associated with such decisions remain unclear. To test the hypothesis that a pragmatic propofol-based sedation regimen with restricted polypharmacy (RP; ie, prohibits additional infusions unless a predefined propofol dosage threshold is exceeded) would increase coma-and ventilator-free days compared with usual care (UC), we performed a retrospective cohort study of adults admitted to intensive care units (ICUs) of a tertiary-level medical center who were mechanically ventilated, initiated on propofol infusion, and had >50% probability of need for continued ventilation for the next 24 hours. We compared RP to UC, adjusting for baseline and time-varying confounding (demographics, care unit, calendar time of admission, vitals, laboratories, other interventions such as vasopressors and fluids, and more) through inverse probability weighting in a target trial framework. Ventilator-free days and coma-free days within 30 days of intubation and in-hospital mortality were the outcomes of interest. A total of 7974 patients were included in the analysis, of which 3765 followed the RP strategy until extubation. In the full cohort under UC, mean coma-free days were 23.5 (95% confidence interval [CI], [23.3-23.7]), mean ventilator-free days were 20.6 (95% CI, [20.4-20.8]), and the in-hospital mortality rate was 22.0% (95% CI, [21.2-22.8]). We estimated that an RP strategy would increase mean coma-free days by 1.0 days (95% CI, [0.7-1.3]) and ventilator-free days by 1.0 days (95% CI, [0.7-1.3]) relative to UC in our cohort. Our estimate of the confounding-adjusted association between RP and in-hospital mortality was uninformative (-0.5%; 95% CI, [-3.0 to 1.9]). Compared with UC, RP was associated with more coma- and ventilator-free days. Restricting addition of adjunct infusions to propofol may represent a viable strategy to reduce duration of coma and mechanical ventilation. These hypothesis-generating findings should be confirmed in a randomized control trial.
Sections du résumé
BACKGROUND
Adverse effects of excessive sedation in critically ill mechanically ventilated patients are well described. Although guidelines strongly recommend minimizing sedative use, additional agents are added as infusions, often empirically. The tradeoffs associated with such decisions remain unclear.
METHODS
To test the hypothesis that a pragmatic propofol-based sedation regimen with restricted polypharmacy (RP; ie, prohibits additional infusions unless a predefined propofol dosage threshold is exceeded) would increase coma-and ventilator-free days compared with usual care (UC), we performed a retrospective cohort study of adults admitted to intensive care units (ICUs) of a tertiary-level medical center who were mechanically ventilated, initiated on propofol infusion, and had >50% probability of need for continued ventilation for the next 24 hours. We compared RP to UC, adjusting for baseline and time-varying confounding (demographics, care unit, calendar time of admission, vitals, laboratories, other interventions such as vasopressors and fluids, and more) through inverse probability weighting in a target trial framework. Ventilator-free days and coma-free days within 30 days of intubation and in-hospital mortality were the outcomes of interest.
RESULTS
A total of 7974 patients were included in the analysis, of which 3765 followed the RP strategy until extubation. In the full cohort under UC, mean coma-free days were 23.5 (95% confidence interval [CI], [23.3-23.7]), mean ventilator-free days were 20.6 (95% CI, [20.4-20.8]), and the in-hospital mortality rate was 22.0% (95% CI, [21.2-22.8]). We estimated that an RP strategy would increase mean coma-free days by 1.0 days (95% CI, [0.7-1.3]) and ventilator-free days by 1.0 days (95% CI, [0.7-1.3]) relative to UC in our cohort. Our estimate of the confounding-adjusted association between RP and in-hospital mortality was uninformative (-0.5%; 95% CI, [-3.0 to 1.9]).
CONCLUSIONS
Compared with UC, RP was associated with more coma- and ventilator-free days. Restricting addition of adjunct infusions to propofol may represent a viable strategy to reduce duration of coma and mechanical ventilation. These hypothesis-generating findings should be confirmed in a randomized control trial.
Identifiants
pubmed: 37014964
doi: 10.1213/ANE.0000000000006419
pii: 00000539-202306000-00015
doi:
Substances chimiques
Propofol
YI7VU623SF
Hypnotics and Sedatives
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1115-1121Informations de copyright
Copyright © 2023 International Anesthesia Research Society.
Déclaration de conflit d'intérêts
The authors declare no conflicts of interest.
Références
Shehabi Y, Bellomo R, Reade MC, et al. Early intensive care sedation predicts long-term mortality in ventilated critically ill patients. Am J Respir Crit Care Med. 2012;186:724–731.
Shehabi Y, Chan L, Kadiman S, et al. Sedation depth and long-term mortality in mechanically ventilated critically ill adults: a prospective longitudinal multicentre cohort study. Intensive Care Med. 2013;39:910–918.
Devlin JW, Skrobik Y, Gelinas C, et al. Clinical practice guidelines for the prevention and management of pain, agitation/sedation, delirium, immobility, and sleep disruption in adult patients in the ICU. Crit Care Med. 2018;46:e825–e873.
Aragon RE, Proano A, Mongilardi N, et al. Sedation practices and clinical outcomes in mechanically ventilated patients in a prospective multicenter cohort. Crit Care. 2019;23:130.
Hofer MM, Wieruszewski PM, Nei SD, et al. Intensive care unit sedation practices at a large, tertiary academic center. J Intensive Care Med. 2022;37:1383–1396.
Miller MA, Govindan S, Watson SR, et al. ABCDE, but in that order? A cross-sectional survey of Michigan intensive care unit sedation, delirium, and early mobility practices. Ann Am Thorac Soc. 2015;12:1066–1071.
Vincent JL, Shehabi Y, Walsh TS, et al. Comfort and patient-centred care without excessive sedation: the eCASH concept. Intensive Care Med. 2016;42:962–971.
Karamchandani K, Dalal R, Patel J, Modgil P, Quintili A. Challenges in sedation management in critically ill patients with COVID-19: a brief review. Curr Anesthesiol Rep. 2021;11:107–115.
Hanidziar D, Bittner EA. Sedation of mechanically ventilated COVID-19 patients: challenges and special considerations. Anesth Analg. 2020;131:e40–e41.
Kapp CM, Zaeh S, Niedermeyer S, Punjabi NM, Siddharthan T, Damarla M. The use of analgesia and sedation in mechanically ventilated patients with COVID-19 acute respiratory distress syndrome. Anesth Analg. 2020;131:e198–e200.
Bose S, Kelly L, Shahn Z, et al. Sedative polypharmacy mediates the effect of mechanical ventilation on delirium in critically ill COVID-19 patients: a retrospective cohort study. Acta Anaesthesiol Scand. 2022;66:1099–1106.
Hernan MA. Methods of public health research—strengthening causal inference from observational data. N Engl J Med. 2021;385:1345–1348.
Hernan MA, Robins JM. Using big data to emulate a target trial when a randomized trial is not available. Am J Epidemiol. 2016;183:758–764.
Johnson A, Bulgarelli L, Pollard T, et al. MIMIC-IV-ED (Version 1.0). PhysioNet. 2021. https://doi.org/10.13026/77z6-9w59
doi: 10.13026/77z6-9w59
Hernan MA, Sauer BC, Hernandez-Diaz S, Platt R, Shrier I. Specifying a target trial prevents immortal time bias and other self-inflicted injuries in observational analyses. J Clin Epidemiol. 2016;79:70–75.
Rudolph JE, Cartus A, Bodnar LM, Schisterman EF, Naimi AI. The role of the natural course in causal analysis. Am J Epidemiol. 2021;191:341–348.
Hernan MA, Robins JM. Estimating causal effects from epidemiological data. J Epidemiol Community Health. 2006;60:578–586.
Cain LE, Robins JM, Lanoy E, et al. When to start treatment? A systematic approach to the comparison of dynamic regimes using observational data. Int J Biostat. 2010;6:Article 18.
Orellana L, Rotnitzky A, Robins JM. Dynamic regime marginal structural mean models for estimation of optimal dynamic treatment regimes, part I: main content. Int J Biostat. 2010;6:Article 8.
Robins J. A new approach to causal inference in mortality studies with a sustained exposure period—application to control of the healthy worker survivor effect. Math Model. 1986;7:1393–1512.
Johnson AE, Kramer AA, Clifford GD. A new severity of illness scale using a subset of acute physiology and chronic health evaluation data elements shows comparable predictive accuracy. Crit Care Med. 2013;41:1711–1718.
Knaus WA, Wagner DP, Draper EA, et al. The APACHE III prognostic system. Risk prediction of hospital mortality for critically ill hospitalized adults. Chest. 1991;100:1619–1636.
Jakob SM, Ruokonen E, Grounds RM, et al. Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials. JAMA. 2012;307:1151–1160.
Hughes CG, Mailloux PT, Devlin JW, et al. Dexmedetomidine or propofol for sedation in mechanically ventilated adults with sepsis. N Engl J Med. 2021;384:1424–1436.
Hughes CG, Hayhurst CJ, Pandharipande PP, et al. Association of delirium during critical illness with mortality: multicenter prospective cohort study. Anesth Analg. 2021;133:1152–1161.