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  • 1
    In: Journal of Intensive Care Medicine, SAGE Publications, Vol. 38, No. 3 ( 2023-03), p. 299-306
    Abstract: Preclinical studies suggest that ketamine stimulates breathing. We investigated whether adding a ketamine infusion at low and high doses to propofol sedation improves inspiratory flow and enhances sedation in spontaneously breathing critically ill patients. Methods In this prospective interventional study, twelve intubated, spontaneously breathing patients received ketamine infusions at 5 mcg/kg/min, followed by 10 mcg/kg/min for 1 h each. Airway flow, pressure, and esophageal pressure were recorded during a spontaneous breathing trial (SBT) at baseline, and during the SBT conducted at the end of each ketamine infusion regimen. SBT consisted of one-minute breathing with zero end-expiratory pressure and no pressure support. Changes in inspiratory flow at the pre-specified time points were assessed as the primary outcome. Ketamine-induced change in beta-gamma electroencephalogram power was the key secondary endpoint. We also analyzed changes in other ventilatory parameters respiratory timing, and resistive and elastic inspiratory work of breathing. Results Ketamine infusion of 5 and 10 mcg/kg/min increased inspiratory flow (median, IQR) from 0.36 (0.29-0.46) L/s at baseline to 0.47 (0.32-0.57) L/s and 0.44 (0.33-0.58) L/s, respectively ( p = .013). Resistive work of breathing decreased from 0.4 (0.1-0.6) J/l at baseline to 0.2 (0.1-0.3) J/l after ketamine 10 mcg/kg/min ( p = .042), while elastic work of breathing remained unchanged. Electroencephalogram beta-gamma power (19-44 Hz) increased compared to baseline ( p  〈  .01). Conclusions In intubated, spontaneously breathing patients receiving a constant rate of propofol, ketamine increased inspiratory flow, reduced inspiratory work of breathing, and was associated with an “activated” electroencephalographic pattern. These characteristics might facilitate weaning from mechanical ventilation.
    Type of Medium: Online Resource
    ISSN: 0885-0666 , 1525-1489
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2023
    detail.hit.zdb_id: 2001472-7
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  • 2
    In: Critical Care Medicine, Ovid Technologies (Wolters Kluwer Health), Vol. 50, No. 5 ( 2022-05), p. e434-e444
    Abstract: To evaluate whether different gamma-aminobutyric acidergic (GABAergic) sedatives such as propofol and benzodiazepines carry differential risks of post-extubation delirium in the ICU. DESIGN: Retrospective cohort study. SETTING: Seven ICUs in an academic hospital network, Beth Israel Deaconess Medical Center (Boston, MA). PATIENTS: Ten thousand five hundred and one adult patients mechanically ventilated for over 24 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: 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). CONCLUSIONS: 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.
    Type of Medium: Online Resource
    ISSN: 0090-3493
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 2034247-0
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