Effect of flumazenil on diaphragm electrical activation during weaning from mechanical ventilation after acute respiratory distress syndrome

Rozé, Hadrien; Germain, Arnaud; Perrier, Virginie; Dewitte, Antoine; Joannès-Boyau, Olivier; Fleureau, Catherine; Ouattara, Alexandre

doi:10.1093/bja/aeu374

Cited by 17 publications

(14 citation statements)

References 29 publications

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“…Additionally, respiratory drive affects the pathophysiology and clinical outcome of ARDS (Spinelli et al, 2020). Dexmedetomidine was not found to affect the respiratory rate or gas exchange in ICU patients compared to a placebo (Venn et al, 2000) and did not affect the hypercapnic ventilatory response in healthy volunteers (Hsu et al, 2004); conversely, sedation with midazolam or propofol might suppress the respiratory drive in patients on mechanical ventilation (Migliari et al, 2009;Rozé et al, 2015). Another biological rationale for the potential benefit of dexmedetomidine is based on the experimental evidence of protective effects against neuronal, myocardial, and renal injury (Si et al, 2014;Ren et al, 2016), the reduction in the levels of inflammatory mediators after cardiopulmonary bypass; and the reduced mortality rates observed in animal models (Taniguchi et al, 2004;Ueki et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Comparative Effectiveness of Midazolam, Propofol, and Dexmedetomidine in Patients With or at Risk for Acute Respiratory Distress Syndrome: A Propensity Score-Matched Cohort Study

Zhong

et al. 2021

Front. Pharmacol.

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Background: Sedatives are commonly used in patients with or at risk for acute respiratory distress syndrome (ARDS) during mechanical ventilation. To systematically compare the outcomes of sedation with midazolam, propofol, and dexmedetomidine in patients with or at risk for ARDS.Methods: We developed a dataset of real-world data to enable the comparison of the effectiveness and safety of sedatives and the associated outcomes from the MIMIC-III database and the eICU Collaborative Research database. We performed a systematic study with six cohorts to estimate the relative risks of outcomes among patients administered different sedatives. Propensity score matching was performed to generate a balanced 1:1 matched cohort and to identify potential prognostic factors. The outcomes included hospital mortality, duration of mechanical ventilation, length of intensive care unit stay, length of hospitalization, and likelihood of being discharged home.Results: We performed 60 calibrated analyses among all groups and outcomes with 17,410 eligible patients. Sedation with dexmedetomidine was associated with a lower in-hospital mortality rate than sedation with midazolam and propofol or sedation without dexmedetomidine (p < 0.001). When compared with no sedation, the use of midazolam, propofol or dexmedetomidine was associated with a longer ICU stay and longer hospitalization duration (p < 0.01). Patients treated with midazolam were relatively less likely to be discharged home (p < 0.05).Conclusion: Patients treated with dexmedetomidine had a reduced risk of mortality. These data suggest that dexmedetomidine may be the preferred sedative in patients with or at risk for ARDS.

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Section: Discussionmentioning

confidence: 99%

Comparative Effectiveness of Midazolam, Propofol, and Dexmedetomidine in Patients With or at Risk for Acute Respiratory Distress Syndrome: A Propensity Score-Matched Cohort Study

Zhong

et al. 2021

Front. Pharmacol.

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“…Sedation exerts a well-known inhibitory effect on diaphragmatic contractility [12,13]. Diaphragmatic activity may be jeopardised by a residual sedation, especially in the early weaning period [14]. Last, TFdi was negatively but not significantly associated with early ICU treatments (neuromuscular blockers or vasopressor use before inclusion) and complications (ventilator-associated pneumonia and prolonged ventilation), which may be risk factors for diaphragmatic atrophy and weakness [15].…”

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confidence: 99%

Determinants of diaphragm thickening fraction during mechanical ventilation: an ancillary study of a randomised trial

et al. 2017

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Ultrasonography of the diaphragm is the subject of a growing interest in the intensive care unit (ICU) setting [1-6]. Observing the diaphragm in its zone of apposition allows measurement of its thickness and computation of its thickening fraction (TFdi), which depends on diaphragmatic activity [3] and reflects the diaphragm work of breathing [1]. A recent study showed that the TFdi correlated well with the endotracheal pressure variation generated by phrenic stimulation [6]. This index was also proposed for clinical evaluation of diaphragm weakness to detect ventilator-induced diaphragmatic dysfunction (VIDD) and predict difficult weaning [3, 4]. However, it remains unclear whether increased thickening in this setting only reflects a better intrinsic diaphragmatic strength, or if it also suggests enhanced work of breathing in response to increased cardiorespiratory workload. Furthermore, some authors suggested that VIDD could be thought as the "respiratory" manifestation of a global neuromuscular weakness [4, 7], but its relationship with ICU-acquired limb weakness is not straightforward [5]. The present study had a dual objective: first, to explore the correlation between ICU-acquired limb weakness (as assessed by the Medical Research Council (MRC) score) and diaphragm thickening (as assessed by TFdi); second, to assess the association of clinical variables with TFdi during mechanical ventilation. This was a planned a priori ancillary study performed in one (Henri Mondor University Hospital, Creteil, France) of the nine participating centres of the B-type natriuretic peptide for the fluid Management of Weaning (BMW) trial [8]. We explored diaphragm thickening at the very beginning of weaning in 55 consecutive participants enrolled in this trial at this centre when ultrasonography was available. Ultrasonography was performed after 5 min of minimal respiratory support (pressure support set at 7 cmH 2 O with zero end expiratory pressure), using an Envisor system (Philips Ultrasound, Bothell, WA, USA) equipped with a 12 MHz high-resolution ultrasound linear probe. After locating the right hemi-diaphragm zone of apposition, the end-inspiratory and end-expiratory thicknesses were measured, allowing calculation of the TFdi of each patient, as previously reported [1]. The ultrasonography scans were performed by two intensivists, both experienced in ultrasonography (E. Vivier or F. Roche-Campo) and all measurements were analysed by E. Vivier. ICU-acquired weakness was screened in cooperating patients by clinical assessment of the limb strength, using the MRC score [9]. The most clinically relevant variables concerning diaphragmatic strength were used for the statistical analysis.

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“…The anesthetic agent, sodium midazolam, can affect respiratory depression. 13 However, in the current study, both MV and control animals were anesthetized with sodium midazolam, thus comparisons between the groups are valid. Furthermore, the drinking reflex was preserved, indicating that there was no or minimal depression of diaphragm activity due to the drug.…”

Section: Discussionmentioning

confidence: 95%

High-Level Pressure Support Ventilation Attenuates Ventilator-Induced Diaphragm Dysfunction in Rabbits

Zhu

et al. 2015

The American Journal of the Medical Sciences

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Abstract:Background:The effects of different modes of mechanical ventilation in the same ventilatory support level on ventilator-induced diaphragm dysfunction onset were assessed in healthy rabbits.Methods:Twenty New Zealand rabbits were randomly assigned to 4 groups (n = 5 in each group). Group 1: no mechanical ventilation; group 2: controlled mechanical ventilation (CMV) for 24 hours; group 3: assist/control ventilation (A/C) mode for 24 hours; group 4: high-level pressure support ventilation (PSV) mode for 24 hours. Heart rate, mean arterial blood pressure, PH, partial pressure of arterial oxygen/fraction of inspired oxygen and partial pressure of arterial carbon dioxide were monitored and diaphragm electrical activity was analyzed in the 4 groups. Caspase-3 was evaluated by protein analysis and diaphragm ultra structure was assessed by electron microscopy.Results:The centroid frequency and the ratio of high frequency to low frequency were significantly reduced in the CMV, A/C and PSV groups (P < 0.001). The percent change in centroid frequency was significantly lower in the PSV group than in the CMV and A/C groups (P = 0.001 and P = 0.028, respectively). Electromyography of diaphragm integral amplitude decreased by 90% ± 1.48%, 67.8% ± 3.13% and 70.2% ± 4.72% in the CMV, A/C and PSV groups, respectively (P < 0.001). Caspase-3 protein activation was attenuated in the PSV group compared with the CMV and A/C groups (P = 0.035 and P = 0.033, respectively). Irregular swelling of mitochondria along with fractured and fuzzy cristae was observed in the CMV group, whereas mitochondrial cristae were dense and rich in the PSV group. The mitochondrial injury scores (Flameng scores) in the PSV group were the lowest among the 3 ventilatory groups (0.93 ± 0.09 in PSV versus 2.69 ± 0.05 in the CMV [P < 0.01] and PSV versus A/C groups [2.02 ± 0.08, P < 0.01]).Conclusions:The diaphragm myoelectric activity was reduced in the PSV group, although excessive oxidative stress and ultra-structural changes of diaphragm were found. However, partial diaphragm electrical activity was retained and diaphragm injury was minimized using the PSV mode.

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Effect of flumazenil on diaphragm electrical activation during weaning from mechanical ventilation after acute respiratory distress syndrome

Cited by 17 publications

References 29 publications

Comparative Effectiveness of Midazolam, Propofol, and Dexmedetomidine in Patients With or at Risk for Acute Respiratory Distress Syndrome: A Propensity Score-Matched Cohort Study

Comparative Effectiveness of Midazolam, Propofol, and Dexmedetomidine in Patients With or at Risk for Acute Respiratory Distress Syndrome: A Propensity Score-Matched Cohort Study

Determinants of diaphragm thickening fraction during mechanical ventilation: an ancillary study of a randomised trial

High-Level Pressure Support Ventilation Attenuates Ventilator-Induced Diaphragm Dysfunction in Rabbits

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