Differential Effects of Gamma-Aminobutyric Acidergic Sedatives on Risk of Post-Extubation Delirium in the ICU: A Retrospective Cohort Study From a New England Health Care Network.
Journal
Critical care medicine
ISSN: 1530-0293
Titre abrégé: Crit Care Med
Pays: United States
ID NLM: 0355501
Informations de publication
Date de publication:
01 05 2022
01 05 2022
Historique:
pubmed:
5
1
2022
medline:
3
5
2022
entrez:
4
1
2022
Statut:
ppublish
Résumé
To evaluate whether different gamma-aminobutyric acidergic (GABAergic) sedatives such as propofol and benzodiazepines carry differential risks of post-extubation delirium in the ICU. Retrospective cohort study. Seven ICUs in an academic hospital network, Beth Israel Deaconess Medical Center (Boston, MA). Ten thousand five hundred and one adult patients mechanically ventilated for over 24 hours. None. We tested the hypothesis that benzodiazepine versus propofol-based sedation is associated with fewer delirium-free days within 14 days after extubation. Further, we hypothesized that the measured sedation level evoked by GABAergic drugs is a better predictor of delirium than the drug dose administered. The proportion of GABAergic drug-induced deep sedation was defined as the ratio of days with a mean Richmond Agitation-Sedation Scale of less than or equal to -3 during mechanical ventilation. Multivariable regression and effect modification analyses were used. Delirium-free days were lower in patients who received a high proportion of deep sedation using benzodiazepine compared with propofol-based sedation (adjusted absolute difference, -1.17 d; 95% CI, -0.64 to -1.69; p < 0.001). This differential effect was magnified in elderly patients (age > 65) and in patients with liver or kidney failure (p-for-interaction < 0.001) but not observed in patients who received a low proportion of deep sedation (p = 0.95). GABAergic-induced deep sedation days during mechanical ventilation was a better predictor of post-extubation delirium than the GABAergic daily average effective dose (area under the curve 0.76 vs 0.69; p < 0.001). Deep sedation during mechanical ventilation with benzodiazepines compared with propofol is associated with increased risk of post-extubation delirium. Our data do not support the view that benzodiazepine-based compared with propofol-based sedation in the ICU is an independent risk factor of delirium, as long as deep sedation can be avoided in these patients.
Identifiants
pubmed: 34982739
doi: 10.1097/CCM.0000000000005425
pii: 00003246-202205000-00028
doi:
Substances chimiques
Hypnotics and Sedatives
0
Benzodiazepines
12794-10-4
Propofol
YI7VU623SF
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e434-e444Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2022 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
Déclaration de conflit d'intérêts
Dr. Sarge received funding from Christie & Young PC, Intermountain Medical Center, and Downs Rachlin Martin PLLC. Dr. Subramaniam’s institution received funding from the National Institutes of Health and Mallinckrodt Pharmaceuticals. Dr. Eikermann received funding from Jeffrey and Judy Buzen and Merck. The remaining authors have disclosed that they do not have any potential conflicts of interest.
Références
Page VJ, Ely EW, Gates S, et al.: Effect of intravenous haloperidol on the duration of delirium and coma in critically ill patients (Hope-ICU): A randomised, double-blind, placebo-controlled trial. Lancet Respir Med. 2013; 1:515–523
Hopkins RO, Suchyta MR, Kamdar BB, et al.: Instrumental activities of daily living after critical illness: A systematic review. Ann Am Thorac Soc. 2017; 14:1332–1343
van den Boogaard M, Tilburgs B: Can we accurately predict ICU delirium? Intensive Crit Care Nurs. 2020; 57:102809
Pearson SD, Patel BK: Evolving targets for sedation during mechanical ventilation. Curr Opin Crit Care. 2020; 26:47–52
Ouellette DR, Patel S, Girard TD, et al.: Liberation from mechanical ventilation in critically ill adults: An official American College of Chest Physicians/American Thoracic Society Clinical Practice Guideline: Inspiratory pressure augmentation during spontaneous breathing trials, protocols minimizing sedation, and noninvasive ventilation immediately after extubation. Chest. 2017; 151:166–180
Chanques G, Constantin JM, Devlin JW, et al.: Analgesia and sedation in patients with ARDS. Intensive Care Med. 2020; 46:2342–2356
Page V: Sedation in mechanically ventilated patients with COVID-19. Lancet Respir Med. 2021; 9:218–219
Hemphill S, McMenamin L, Bellamy MC, et al.: Propofol infusion syndrome: A structured literature review and analysis of published case reports. Br J Anaesth. 2019; 122:448–459
Vasile B, Rasulo F, Candiani A, et al.: The pathophysiology of propofol infusion syndrome: A simple name for a complex syndrome. Intensive Care Med. 2003; 29:1417–1425
Wahr JA, Plunkett JJ, Ramsay JG, et al.: Cardiovascular responses during sedation after coronary revascularization. Incidence of myocardial ischemia and hemodynamic episodes with propofol versus midazolam. Institutions of the McSPI Research Group. Anesthesiology. 1996; 84:1350–1360
Wongtangman K, Santer P, Wachtendorlf L, et al.: Association of sedation, coma, and in-hospital mortality in mechanically ventilated patietns with COVID-19 related acute respiratory distress syndrome. Crit Care Med. 2021; 49:1524-1534
Hughes CG, Mailloux PT, Devlin JW, et al.; MENDS2 Study Investigators: Dexmedetomidine or propofol for sedation in mechanically ventilated adults with sepsis. N Engl J Med. 2021; 384:1424–1436
Kotfis K, Marra A, Ely EW: ICU delirium - a diagnostic and therapeutic challenge in the intensive care unit. Anaesthesiol Intensive Ther. 2018; 50:160–167
Collet MO, Caballero J, Sonneville R, et al.; AID-ICU cohort study co-authors: Prevalence and risk factors related to haloperidol use for delirium in adult intensive care patients: The multinational AID-ICU inception cohort study. Intensive Care Med. 2018; 44:1081–1089
van den Boogaard M, Pickkers P, Slooter AJ, et al.: Development and validation of PRE-DELIRIC (PREdiction of DELIRium in ICu patients) delirium prediction model for intensive care patients: Observational multicentre study. BMJ. 2012; 344:e420
Shehabi Y, Bellomo R, Kadiman S, et al.; Sedation Practice in Intensive Care Evaluation (SPICE) Study Investigators and the Australian and New Zealand Intensive Care Society Clinical Trials Group: Sedation intensity in the first 48 hours of mechanical ventilation and 180-day mortality: A multinational prospective longitudinal cohort study. Crit Care Med. 2018; 46:850–859
Pandharipande P, Cotton BA, Shintani A, et al.: Prevalence and risk factors for development of delirium in surgical and trauma intensive care unit patients. J Trauma. 2008; 65:34–41
Pandharipande P, Shintani A, Peterson J, et al.: Lorazepam is an independent risk factor for transitioning to delirium in intensive care unit patients. Anesthesiology. 2006; 104:21–26
Schreiber MP, Colantuoni E, Bienvenu OJ, et al.: Corticosteroids and transition to delirium in patients with acute lung injury. Crit Care Med. 2014; 42:1480–1486
Pandharipande PP, Pun BT, Herr DL, et al.: Effect of sedation with dexmedetomidine vs lorazepam on acute brain dysfunction in mechanically ventilated patients: The MENDS randomized controlled trial. JAMA. 2007; 298:2644–2653
Zaal IJ, Devlin JW, Hazelbag M, et al.: Benzodiazepine-associated delirium in critically ill adults. Intensive Care Med. 2015; 41:2130–2137
Carson SS, Kress JP, Rodgers JE, et al.: A randomized trial of intermittent lorazepam versus propofol with daily interruption in mechanically ventilated patients. Crit Care Med. 2006; 34:1326–1332
Dubois MJ, Bergeron N, Dumont M, et al.: Delirium in an intensive care unit: A study of risk factors. Intensive Care Med. 2001; 27:1297–1304
Ouimet S, Kavanagh BP, Gottfried SB, et al.: Incidence, risk factors and consequences of ICU delirium. Intensive Care Med. 2007; 33:66–73
Tse AH, Ling L, Joynt GM, et al.: Prolonged infusion of sedatives and analgesics in adult intensive care patients: A systematic review of pharmacokinetic data reporting and quality of evidence. Pharmacol Res. 2017; 117:156–165
Hughes MA, Glass PS, Jacobs JR: Context-sensitive half-time in multicompartment pharmacokinetic models for intravenous anesthetic drugs. Anesthesiology. 1992; 76:334–341
Hill S: Pharmacokinetics of drug infusions. Continuing Education in Anaesthesia Critical Care & Pain. 2004; 4:76–80
Wagner BK, O’Hara DA: Pharmacokinetics and pharmacodynamics of sedatives and analgesics in the treatment of agitated critically ill patients. Clin Pharmacokinet. 1997; 33:426–453
Tse AHW, Ling L, Lee A, et al.: Altered pharmacokinetics in prolonged infusions of sedatives and analgesics among adult critically ill patients: A systematic review. Clin Ther. 2018; 40:1598–1615.e2
Yogaratnam D, Miller MA, Smith BS: The effects of liver and renal dysfunction on the pharmacokinetics of sedatives and analgesics in the critically ill patient. Crit Care Nurs Clin North Am. 2005; 17:245–250
Yogaratnam D, Ditch K, Medeiros K, et al.: The impact of liver and renal dysfunction on the pharmacokinetics and pharmacodynamics of sedative and analgesic drugs in critically ill adult patients. Crit Care Nurs Clin North Am. 2016; 28:183–194
Roberts DJ, Hall RI: Drug absorption, distribution, metabolism and excretion considerations in critically ill adults. Expert Opin Drug Metab Toxicol. 2013; 9:1067–1084
Singh TD, O’Horo JC, Gajic O, et al.: Risk factors and outcomes of critically ill patients with acute brain failure: A novel end point. J Crit Care. 2018; 43:42–47
Zaporowska-Stachowiak I, Szymański K, Oduah MT, et al.: Midazolam: Safety of use in palliative care: A systematic critical review. Biomed Pharmacother. 2019; 114:108838
Siew ED, Fissell WH, Tripp CM, et al.: Acute kidney injury as a risk factor for delirium and coma during critical illness. Am J Respir Crit Care Med. 2017; 195:1597–1607
Morandi A, Brummel NE, Ely EW: Sedation, delirium and mechanical ventilation: The ‘ABCDE’ approach. Curr Opin Crit Care. 2011; 17:43–49
Balas MC, Vasilevskis EE, Olsen KM, et al.: Effectiveness and safety of the awakening and breathing coordination, delirium monitoring/management, and early exercise/mobility bundle. Crit Care Med. 2014; 42:1024–1036
Pandharipande PP, Patel MB, Barr J: Management of pain, agitation, and delirium in critically ill patients. Pol Arch Med Wewn. 2014; 124:114–123
Treggiari MM, Romand JA, Yanez ND, et al.: Randomized trial of light versus deep sedation on mental health after critical illness. Crit Care Med. 2009; 37:2527–2534
Barr J, Fraser GL, Puntillo K, et al.; American College of Critical Care Medicine: Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care Med. 2013; 41:263–306
Hirschtritt ME, Olfson M, Kroenke K: Balancing the risks and benefits of benzodiazepines. JAMA. 2021; 325:347–348
Shehabi Y, Howe BD, Bellomo R, et al.; ANZICS Clinical Trials Group and the SPICE III Investigators: Early sedation with dexmedetomidine in critically ill patients. N Engl J Med. 2019; 380:2506–2517
Ronan KP, Gallagher TJ, George B, et al.: Comparison of propofol and midazolam for sedation in intensive care unit patients. Crit Care Med. 1995; 23:286–293
Pun BT, Badenes R, Heras La Calle G, et al.; COVID-19 Intensive Care International Study Group: Prevalence and risk factors for delirium in critically ill patients with COVID-19 (COVID-D): A multicentre cohort study. Lancet Respir Med. 2021; 9:239–250
Needham DM, Davidson J, Cohen H, et al.: Improving long-term outcomes after discharge from intensive care unit: Report from a stakeholders’ conference. Crit Care Med. 2012; 40:502–509
Devlin JW, Skrobik Y, Gélinas 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
Shehabi Y, Bellomo R, Reade MC, et al.; Sedation Practice in Intensive Care Evaluation (SPICE) Study Investigators; ANZICS Clinical Trials Group: 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, Bellomo R, Reade MC, et al.; Sedation Practice in Intensive Care Evaluation Study Investigators; Australian and New Zealand Intensive Care Society Clinical Trials Group: Early goal-directed sedation versus standard sedation in mechanically ventilated critically ill patients: A pilot study*. Crit Care Med. 2013; 41:1983–1991
Wongtangman K, Grabitz SD, Hammer M, et al.; SICU Optimal Mobilization Team (SOMT) Group: Optimal sedation in patients who receive neuromuscular blocking agent infusions for treatment of acute respiratory distress syndrome-a retrospective cohort study from a New England Health Care Network. Crit Care Med. 2021; 49:1137–1148
Huang DT, Angus DC, Moss M, et al.; Reevaluation of Systemic Early Neuromuscular Blockade Protocol Committee and the National Institutes of Health National Heart, Lung, and Blood Institute Prevention and Early Treatment of Acute Lung Injury Network Investigators: Design and rationale of the reevaluation of systemic early neuromuscular blockade trial for acute respiratory distress syndrome. Ann Am Thorac Soc. 2017; 14:124–133
Li Y, Ma J, Jin Y, et al.: Benzodiazepines for treatment of patients with delirium excluding those who are cared for in an intensive care unit. Cochrane Database Syst Rev. 2020; 2:CD012670
Campbell NL, Perkins AJ, Khan BA, et al.: Deprescribing in the pharmacologic management of delirium: A randomized trial in the intensive care unit. J Am Geriatr Soc. 2019; 67:695–702
Coursin DB, Skrobik Y: What is safe sedation in the ICU? N Engl J Med. 2019; 380:2577–2578
Colantuoni E, Dinglas VD, Ely EW, et al.: Statistical methods for evaluating delirium in the ICU. Lancet Respir Med. 2016; 4:534–536
Jaiswal SJ, Vyas AD, Heisel AJ, et al.: Ramelteon for prevention of postoperative delirium: A randomized controlled trial in patients undergoing elective pulmonary thromboendarterectomy. Crit Care Med. 2019; 47:1751–1758
van den Boogaard M, Slooter AJC, Brüggemann RJM, et al.; REDUCE Study Investigators: Effect of haloperidol on survival among critically ill adults with a high risk of delirium: The REDUCE randomized clinical trial. JAMA. 2018; 319:680–690
Devlin JW, Needham DM: Long-term outcomes after delirium in the ICU: Addressing gaps in our knowledge. Am J Respir Crit Care Med. 2021; 204:383–385
Wolters AE, van Dijk D, Pasma W, et al.: Long-term outcome of delirium during intensive care unit stay in survivors of critical illness: A prospective cohort study. Crit Care. 2014; 18:R125