Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1
VASILIKI TSOLAKI
 -- 2462 2022-10-14 11:59:27 |
2 update references and layout
Rita Xu
 Meta information modification 2462 2022-10-18 05:35:32 |

Video Upload Options

We provide professional Video Production Services to translate complex research into visually appealing presentations. Would you like to try it?
No, upload directly Yes

Confirm

Are you sure to Delete?
Yes No
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Tsolaki, V.;  Zakynthinos, G.E.;  Papadonta, M.;  Bardaka, F.;  Fotakopoulos, G.;  Pantazopoulos, I.;  Makris, D.;  Zakynthinos, E. Neuromuscular Blocking Agents Use in ARDS. Encyclopedia. Available online: https://encyclopedia.pub/entry/29391 (accessed on 16 November 2024).
Tsolaki V,  Zakynthinos GE,  Papadonta M,  Bardaka F,  Fotakopoulos G,  Pantazopoulos I, et al. Neuromuscular Blocking Agents Use in ARDS. Encyclopedia. Available at: https://encyclopedia.pub/entry/29391. Accessed November 16, 2024.
Tsolaki, Vasiliki, George E. Zakynthinos, Maria-Eirini Papadonta, Fotini Bardaka, George Fotakopoulos, Ioannis Pantazopoulos, Demosthenes Makris, Epaminondas Zakynthinos. "Neuromuscular Blocking Agents Use in ARDS" Encyclopedia, https://encyclopedia.pub/entry/29391 (accessed November 16, 2024).
Tsolaki, V.,  Zakynthinos, G.E.,  Papadonta, M.,  Bardaka, F.,  Fotakopoulos, G.,  Pantazopoulos, I.,  Makris, D., & Zakynthinos, E. (2022, October 14). Neuromuscular Blocking Agents Use in ARDS. In Encyclopedia. https://encyclopedia.pub/entry/29391
Tsolaki, Vasiliki, et al. "Neuromuscular Blocking Agents Use in ARDS." Encyclopedia. Web. 14 October, 2022.
Neuromuscular Blocking Agents Use in ARDS
Edit
This entry is adapted from the peer-reviewed paper 10.3390/jpm12091538

Acute respiratory distress syndrome (ARDS) accounts for a quarter of mechanically ventilated patients, while during the pandemic, it overwhelmed the capacity of intensive care units (ICUs). Lung protective ventilation (low tidal volume, positive-end expiratory pressure titrated to lung mechanics and oxygenation, permissive hypercapnia) is a non-pharmacological approach that is the gold standard of management. Among the pharmacological treatments, the use of neuromuscular blocking agents (NMBAs), although extensively studied, has not yet been well clarified.

neuromuscular blocking agents muscular relaxants ARDS survival lung injury

1. Introduction

The acute respiratory distress syndrome (ARDS) was first described in 1967 as a condition of respiratory failure that resembles the respiratory distress syndrome in infants [1]. The syndrome may originate from pulmonary (pneumonia, aspiration and chemical inhalational insults) or extra-pulmonary (trauma, burns, sepsis and pancreatitis) causes and it is acute in onset (within five days of the illness onset/insult). The inflammatory process results in increased vascular permeability (thus, a non-cardiac origin), leading to alveolar infiltration, increased lung weight and the loss of aerated lung tissue. Bilateral pulmonary infiltrates result in hypoxemia and decreased lung compliance [2].
Annually, ARDS accounts for 10% of intensive care unit (ICU) admissions and 24% of patients receiving mechanical ventilation [3]. Attributable mortality remains high, ranging from 35% to 46% and is associated with a degree of lung impairment [2][3]. Survivors may have significant impairments in their quality of life both regarding physical and neurocognitive functions, derangements that may persist for as long as 5 years after recovery from ARDS [4]. During the last three years, the novel coronavirus disease (COVID-19) has severely burdened healthcare system capacities in many parts of the world. A high proportion of patients require hospitalization, and a small subset will develop severe respiratory failure. Due to its pandemic nature (a substantial number of patients suffering at the same period), COVID-19 ARDS patients have overwhelmed ICUs [5][6][7]. Moreover, a high mortality has been reported in those patients receiving invasive mechanical ventilation (IMV), in the range of 47.9–84.4% [5][6][8].
Irrespective of the cause, a definite ARDS treatment is lacking. Its management mainly relies on supportive care, while lung-protective mechanical ventilation strategy is one of the major prerequisites. This includes the application of a low tidal volume on the mechanical ventilation and monitoring of inspiratory pressures, so that the plateau pressure does not exceed the value of 30 cm H2O and/or the driving pressure is kept below 14 cm H2O [9][10]. The application of higher positive-end expiratory pressure (PEEP), a strategy that has been adopted to minimize atelectrauma in recent decades [11], has been highly debated in ARDS management in the COVID-19 era [12][13][14], while proning became a routine clinical practice, and more than 60% of the patients are proned early after intubation [15]. Concerning pharmacological treatments, apart from the recently endorsed corticosteroids and IL-6 receptor antagonist, conferring a variable, clinically significant, survival benefit to COVID-19 patients [16][17][18], neuromuscular blocking agents (NMBAs) are also being used in the management of ARDS [3]. The rational for their use is to harmonize the patient–ventilator interaction, thus reducing the risk of progression to ventilator-induced lung injury (VILI), and a more homogenous distribution of pressurization during tidal ventilation [19]. The use of paralytics varies widely in everyday clinical practice [3]. Two large randomized clinical trials have conferred a bidirectional change in the clinical use of NMBAs in ARDS, as they report conflicting results mainly concerning mortality [20][21]. COVID-19 provided a “bolus” of ARDS patients.

2. Rationale for NMBA Use in ARDS

In ARDS, the adoption of a lung protective ventilator strategy may diminish the risk of ventilator-induced lung injury and is associated with improved survival [9][10]. The use of NMBAs may facilitate lung protective ventilation, preventing spontaneous respiratory activity, thus limiting the risk of generation of large transpulmonary pressure swings, when strong inspiratory efforts occur. Moreover, expiratory efforts may lead to loss of aeration in dependent lung regions (de-recruitment), if pleural pressure is higher than the applied PEEP [22]. As a consequence, NMBAs may control tidal volumes and PEEP throughout the airways, minimizing the risk of barotrauma, volutrauma and atelectrauma. Finally, abolishing spontaneous efforts, NMBAs harmonize the patient–ventilator interaction. Vigorous spontaneous respiratory efforts may increase global transpulmonary pressures and tidal volumes and cause lung overdistension [23]. The deleterious effects of increased lung stress may also be present at a local level, involving certain lung regions, especially in dependent lung zones when the Pendelluft phenomenon occurs—the redistribution of air in lung regions from adjacent alveoli, causing local overdistension [24]. Moreover, some forms of asynchrony, such as the double triggering–delivery of a second tidal volume before complete exhalation, may result in the delivery of higher than set tidal volumes, increasing the local lung stress in the already-injured lung units [25]. As a result, increased respiratory drive, due to the underlying disease or triggered by increased PaCO2 (permissive hypercapnia), which may aggravate lung injury, is blunted with the use of NMBAs. It should also be mentioned that negative intrathoracic pressures may increase the intrathoracic blood volume, increasing lung perfusion; in the already-injured lung parenchyma, the capillary endothelium is already affected (increased permeability). Thus, additional lung damage occurs from the so-called negative pressure pulmonary edema [26].
Studies with daily interruption of sedation showed that patients had a shorter duration of mechanical ventilation, ICU stay and at least no negative effect on mortality [27][28]. These trials did not exclusively include ARDS patients. On the other hand, in ARDS patients, the decreasing work of breathing decreases the oxygen consumption by the respiratory muscles. It has been found that muscular paralysis results in the decrease in cardiac output and whole-body oxygen consumption, thus it has been speculated that blood flow is redistributed from the respiratory muscles to other vascular beds [29]. Finally, an anti-inflammatory role of NMBAs has been proposed. In patients with moderate and severe ARDS, the early use of muscular relaxants was associated with decreased concentrations of pulmonary and systemic proinflammatory markers, namely IL-1β, IL-6 and IL-8 [30]. Sottile et al., in a secondary analysis of the ARMA study, demonstrated that, in patients with PaO2/FiO2 < 120 mmHg receiving low tidal volume ventilation, a reduction in markers representing endothelial and epithelial lung injury was noted for each day of NMBA use [31]. The effects could be attributed to the decrease in lung inflammation, translated in a reduction in biotrauma, resulting from the optimization of patient–ventilator synchrony, or to a direct anti-inflammatory effect of myorelaxants, as shown in animal studies [32].

3. Data on NMBA Use in ARDS

Seven RCTs have been conducted evaluating the benefits, if any, of NMBA use in ARDS patients [20][21][22][30][33][34][35]. The earliest four studies were performed in France [21][22][30][34], two subsequent studies in China [33][35] and the latest, also including the larger number of patients, was performed in USA [20]. The studies have provided conflicting results, so that they have changed the clinical practice in a bidirectional way. Especially when considering the most influential ones (ACURASYS and ROSE study) with the highest recruitment, certain differences have been addressed, although the design of the ROSE study was carefully selected to allow direct comparisons to ACURASYS [20][21].
In the first study in the field, Gainnier et al. randomized 56 patients with moderate and severe ARDS within 36 h of the patients meeting the eligibility criteria. The patients assigned to the NMBAs group received cisatracurium at a dose of 5 μg/kg/min (cumulative dose of 1324 ± 197 mg) after a bolus infusion of 50 mg. The study found that the early use of NMBAs resulted in sustained improvements in oxygenation after 48 h of infusion, persisting during the 120 h of the study period. Hospital mortality on day 28th, 60th and ICU mortality did not differ (Table 1).
Table 1. Patient characteristics and outcomes in the seven randomized controlled trials and the COVID-19 ARDS studies concerning NMBA use in ARDS.
  Patients Primary End Point Time of Inclusion ΝΜΒA Dose Monitoring Duration Sedation PEEPtot VT Pplat PaO2/FiO2 Proning Steroids Barotrauma VAP ICUAW VFD 28/60 Mortality
Gainnier [34] 56 Effect on oxygenation after 120 h Within 36 h meeting inclusion criteria cis 50 mg bolus TOF every 8 h 48 midazolam sufentanil 12.3 ± 3 7.1 ± 1.1 27.1 130 ± 34 14.3% 7.1% 0 46% 0 D28: 3.7 ± 37.2 D28: 35.7%
2004 PaO2/FiO2 < 150 mmHg       5 μg/kg/min Ramsey 6                       D60: 19 ± 320.3 D60: 46.4%
                                      ICU: 46.4%
          actual: 1324 ± 197       11.4 ± 2.5 7.4 ± 31.9 26.1 ± 4 119 ± 31 14.3% 14.3% 1 57% 0 D28: 1.7 ± 35.3 (NS) D28: 60.7 (p = 0.061)
                                    D60: 9.8 ± 16.9 (0.071) D60: 64.3% (p = 0.18)
                                      ICU: 71.4% (p = 0.057)
Forel [30]                           5.5%          
2006 36 Effect on pulmonary and systemic proinflammatory cytokines 48 h of ARDS onset cis bolus 0.2 mg/kg TOF every 8 h 48 h   13.2 ± 2.7 6.5 ± 0.7 27.5 ± 4.4   0   0   1 D28: 6 ± 8.6 ICU: 27.8%
  PaO2/FiO2 < 200 mmHg       5 μg/kg/min       11 ± 2.7 (p < 0.05) 7 ± 30.7 24.8 ± 35.7     0 0   1 D28: 5.4 ± 6.4 (ns) ICU: 55.6% (NS)
Guervilli [22] 30 Effect on respiratory mechanics 48 h of ARDS onset cis bolus 15 mg TOF 48 h midazolam/sufentanil 11 (10–11.5) 6.2 (5.9–6.8 23 (19–26) 158 (131–185)         D28: 7 (0–20) ICU: 38%
2017 PaO2/FiO2 100–150 mmHg       37.5 mg/h Ramsey 6           150 (121–187)           D28: 8(0–18) ICU: 27% (p = 0.6)
Rao [35] 41     vecuronium actual: 1595 mg (1221–1830)       7.84 ± 2.94             4.2%   D28: 17.9 ± 2.77.4 D28: 4.2%
2016 ARDS pts                                   90: 4.2%
                                0   D28: 17.1 ± 8.2 D28: 11.8%
                  5.88 ± 1.96                   90: 17.6%
Lyu [33]
2014		 96     vecuronium 0.05 mg/kg/h   24–48 h         140.95 ± 26.97             D21: 16.7%
  PaO2/FiO2 < 200 mmHg (24)                                   D21: 25% (p = 0.035)
  PaO2/FiO2 < 100 mmHg (24)                     144.33 ± 24.09             D21: 20.8%
                                      D21: 50% (0.477)
Papazian [21] 340   48 h of ARDS onset cis bolus 15 mg Ramsay 6   midazolame 9.2 ± 3.2 6.55 ± 1.12 25 ± 5.1 106 ± 36 28% 16% 4%   28D: 70.8% 28D: 10.6 ± 9.7 28D: 23.7%
2010 PaO2/FiO2 < 150 mmHg 90-day mortality actual inclusion time: 16 h   37.5 mg/h     sufentanil                 icu discharge: 64.3% 90D: 53.1 ± 35.8 ICU: 29.4%
                ketamin                     In hospital: 32.2%
                propofole                      
                  9.2 ± 3.5 6.48 ± 0.92 24.4 ± 4.7 115 ± 41 29% 23%(p = 0.1) 11.7% (p = 0.01)   28D:67.5% (p = 0.64) 28D: 8.5 ± 9.4 (p = 0.04) 28D: 33.3% (p = 0.05)
                                  icu discharge: 68.5% (p = 0.51) 90D: 44.6 ± 37.5 (p = 0.03) ICU: 38.9% (p = 0.06)
                                      In hospital: 32.2% (p = 0.08)
ROSE [20] 1006 90-day mortality 48 h of ARDS onset cis bolus: 15 mg Ramsey 5–6 48 h   12.6 ± 3.6 6.3 ± 0.9 25.5 ± 6.0 98.7 ± 27.9 16.8% 17% 4%   D7: 41% D28: 9.6 ± 10.4 D90: 42.5%
2019 PaO2/FiO2 < 150 mmHg   actual randomization time: 8 h   37.5 mg continuous infusion RASS −5                     D28:46.8% D28: 36.7%
            Ramsey 2–3     12.5 ± 3.5 6.3 ± 0.9 25.7 ± 6.1 99.5 ± 27.9 14.9% 16.4% 6.3%   D7: 31.3% D28:9.9 ± 10.9 D90: 42.8%
            RASS 0 to −1                     D28:27.5% D28: 37%
Courcelle [36] 407 NMBA use         5 days (IQR 2–10) <48 h: 12 (10–14) 6.1 (5.8–6.6) 23 (20–26) 126 (88–162) 65%         D28: 0 (0–16) ICU: 38%
2020 PaO2/FiO2 < 150 mmHg 28-day outcomes                     Propensity cohort 78%        
  COVID-19 ARDS                                    
                  >48 h: 11 (10–13) 6.1 (5.8–6.6) 24 (21–26) 120 (87–157) 90% (p < 0.001)       D28: 0 (0–10) ICU: 41% (p = 0.54)
                          propensity cohort: 80% (p = 0.86)        
Lee [37] 129 ICU mortality         5 days (4–9) survivors: 10 (9–12) 7 (6.2–7.9)   123 (87–197) 16% 92%   53% (superinfection rate) 8.2 ± 9.7 ICU 37%
2022 COVID-19 ARDS                       survivors: 20% 91%         mild ARDS: 20%
                          non-survivors: 10% 94%         moderate ARDS: 40%
                  non-survivors: 10 (10–12) 6.8 (6.2–8.3)   109 (85–134)             severe ARDS: 43%
Li Bassi [38]                                      
2022 1953 90-day mortality             No NMBA: 12 ± 3 7.1 ± 1.4 25.4 ± 5.7 98.1 ± 31.1 8.6% 21.3% 12.4%        
  COVID-19 ARDS (moderate and severe)               No NMBA(PS): 11.9 ± 2.73.1 7.4 ± 1.6 25 ± 2.75.9 86 ± 30.7 10.5% 22.9% 9.6%        
  242 with early NMBA           48 h: 74.4% NMBA: 12.8 ± 3.3 6.9 ± 1.4 26.1 ± 2.75.1 88.5 ± 29.3 21.5% 19.8% 9.6%        
              72 h: 25.6% NMBA (PS): 12.8 (3.3) 6.8 ± 1.4 26.2 ± 2.75 88.6 ± 29.7 21.9% 19% 10.4%        
Nunez-Seisderos [39] 70 survivors with COVID-19 ARDS ICUAW   cis cumulative dose: 739 mg (283–1425)   5 days (2–8)       81 (64–97.75) 91.4% 100%     65.7% IMV DUR: 13 (7–22.5)
Only one patient suffered a pneumothorax in the control group and none of the patients developed any signs of muscle weakness, while there were no differences in the number of patients suffering a ventilator-associated pneumonia (VAP) episode. The second RCT randomized 36 patients with ARDS and PaO2/FiO2 < 200 mmHg to receive NMBAs for 48 h or not. The authors reported that the sustained improvement in oxygenation was accompanied with a reduction in pulmonary and systemic cytokines in patients under NMBAs. Ventilator-free days (VFDs) and ICU mortality (27.8% vs. 55.6%) did not differ (Table 1) [30]. The small sample size may have precluded the numerical difference in mortality to reach a statistical significance. The same study group reported that, in 30 ARDS patients with moderate and severe ARDS, the use of NMBAs increased the mean inspiratory and expiratory transpulmonary pressures, as a result of a stable positive end expiratory pressure with the elimination of expiratory efforts [22]. The changes in lung mechanics were associated with improvements in oxygenation in the NMBA group. The authors point that, by abolishing expiratory efforts, a significant amount of derecruitment during expiration can be achieved [22]. There are two Chinese RCTs using vecuronium as the NMBA: Lyu et al. randomized 96 patients with moderate (48 patients) and severe ARDS (48 patients). The patients with PaO2/FiO2 < 100 mmHg receiving 24–48 h vecuronium presented significant improvements in oxygenation, perfusion and multiple severity scores, while they had also lower 21-day mortality rates (20.8 vs. 50%, p = 0.04) [33]. Both studies did not report significant adverse effects with the use of aminosteroidal NMBAs.
The most robust evidence concerning the use of NMBAs in ARDS patients comes from the two largest RCTs (ACURASYS and ROSE studies), although reporting conflicting results [20][21]. The ACURASYS study was a multicenter RCT, conducted in France, which randomized 340 patients to receive a 48 h of cisatracurium infusion or placebo, within 48 h of ARDS diagnosis [21]. The primary outcome was 90-day mortality. The study team followed the same NMBA administration protocol as the previous studies [22][30][34]. Using a continuous infusion of 37.5 mg (after a bolus of 15 mg) of cisatracurium, as it had been found adequate to sustain paralysis in the previous studies, no peripheral nerve simulation was performed. The authors found that the hazard ratio for death at 90 days in the cisatracurium group compared to the placebo group was 0.68 (95% confidence interval (CI), 0.48 to 0.98; p = 0.04) after adjustment for the baseline PaO2/FiO2, SAPS II and plateau pressures. The crude 90-day mortality was 31.6% (95% CI, 25.2 to 38.8) in the cisatracurium group and 40.7% (95% CI, 33.5 to 48.4) in the placebo group (p = 0.08). Patients in the intervention group had also more VFD in the first 28 days (10.6 ± 9.7 vs. 8.5 ± 9.4, p = 0.04) and an increased hazard ratio for weaning from mechanical ventilation by day 90 (HR 1.41 95% CI 1.08 to 1.83; p = 0.01). Barotrauma was significantly more frequent in the placebo group (4 vs. 11.7%, p = 0.01).
In 2014, the National Heart, Lung and Blood Institute (NHLBI) launched the Prevention and Early Treatment of Acute Lung Injury (PETAL) Network to conduct phase III trials to test treatments with the potential to improve clinical outcomes of patients with or at risk of developing ARDS. PETAL built on a new network (NHLBI ARDS Clinical Trial Network (ARDSNet)) with a focus on early treatment and prevention. Thus, in 2016, PETAL launched the Re-evaluation of Systemic Early Neuromuscular Blockade (ROSE) trial to assess the efficacy and safety of early neuromuscular blockade in reducing mortality and morbidity patients with moderate and severe ARDS [40]. The outcomes were tested on a longer timeframe (up to 12 months). The rational for the conduction of a second trial is summarized below: Firstly, there was a need to re-evaluate the effectiveness of NMBAs in a larger cohort than the one included in ACURASYS study [21]. In view of the change in clinical practice favoring light sedation [27][28], the ROSE protocol intended to compare heavy sedation with additional paralysis with NMBAs to a light sedation protocol adopted in the control group. Thirdly, the patients were randomized if they presented a PaO2/FiO2 <150 mmHg with PEEP application of 8 cm H2O or higher. This is in contrast to the inclusion criterion used in the ACURASYS trial, where hypoxemia was tested with a PEEP of at least 5 cm H2O [21]. This criterion was selected to exclude patients with transient hypoxemia after intubation [40]. The trial enrolled 1006 patients and was stopped for futility after the second interim analysis; the decision was independently made considering the data analyzed and the safety monitoring results. Treatment with NMBAs was not associated with increases in oxygenation variables, nor were there any effects on in hospital mortality or VFM. The incidence of barotrauma did not differ across the patients in both study arms, while patients receiving muscular relaxants presented serious cardiovascular adverse effects (one death from complete heart block and refractory shock) [20]. There are certain differences that may explain the contradictory results in these two RCTs. Firstly, the approach concerning the ARDS treatment was quite different. The amount of PEEP used in ROSE trial was much higher than the one used in the ACURASYS study (12.6 ± 3.6 vs. 9.2 ± 3.2 cm H2O), prone positioning was less frequently used (16% vs. 29%), while the patient enrollment in the ROSE study was too quick (actual time of enrollment was 8 h from meeting eligibility criteria). Some patients might have improved in the next few hours only with the application of the ventilator (i.e., PEEP application) and not be eligible for the study.

References

  1. Ashbaugh, D.G.; Bigelow, D.B.; Petty, T.L.; Levine, B.E. Acute Respiratory distress in adults. Lancet 1967, 2, 319–323.
  2. Fan, E.; Brodie, D.; Slutsky, A.S. Acute Respiratory Distress Syndrome: Advances in Diagnosis and Treatment. JAMA 2018, 319, 698–710.
  3. Bellani, G.; Laffey, J.G.; Pham, T.; Fan, E.; Brochard, L.; Esteban, A.; Gattinoni, L.; van Haren, F.; Larsson, A.; McAuley, D.F.; et al. LUNG SAFE Investigators; ESICM Trials Group. Epidemiology, Patterns of Care, and Mortality for Patients with Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries. JAMA 2016, 315, 788–800.
  4. Herridge, M.S.; Tansey, C.M.; Matté, A.; Tomlinson, G.; Diaz-Granados, N.; Cooper, A.; Guest, C.B.; Mazer, C.D.; Mehta, S.; Stewart, T.E.; et al. Canadian Critical Care Trials Group. Functional disability 5 years after acute respiratory distress syndrome. N. Engl. J. Med. 2011, 364, 1293–1304.
  5. Karagiannidis, C.; Mostert, C.; Hentschker, C.; Voshaar, T.; Malzahn, J.; Schillinger, G.; Klauber, J.; Janssens, U.; Marx, G.; Weber-Carstens, S.; et al. Case characteristics, resource use, and outcomes of 10 021 patients with COVID-19 admitted to 920 German hospitals: An observational study. Lancet Respir. Med. 2020, 8, 853–862.
  6. Richardson, S.; Hirsch, J.S.; Narasimhan, M.; Crawford, J.M.; McGinn, T.; Davidson, K.W.; The Northwell COVID-19 Research Consortium; Barnaby, D.P.; Becker, L.B.; Chelico, J.D.; et al. Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area. JAMA 2020, 323, 2052–2059.
  7. Grasselli, G.; Zangrillo, A.; Zanella, A.; Antonelli, M.; Cabrini, L.; Castelli, A.; Cereda, D.; Coluccello, A.; Foti, G.; Fumagalli, R.; et al. COVID-19 Lombardy ICU Network. Baseline Characteristics and Outcomes of 1591 Patients Infected With SARS-CoV-2 Admitted to ICUs of the Lombardy Region, Italy. JAMA 2020, 323, 1574–1581.
  8. Lim, Z.J.; Subramaniam, A.; Ponnapa Reddy, M.; Blecher, G.; Kadam, U.; Afroz, A.; Billah, B.; Ashwin, S.; Kubicki, M.; Bilotta, F.; et al. Case Fatality Rates for Patients with COVID-19 Requiring Invasive Mechanical Ventilation. A Meta-analysis. Am. J. Respir. Crit. Care Med. 2021, 203, 54–66.
  9. Acute Respiratory Distress Syndrome Network; Brower, R.G.; Matthay, M.A.; Morris, A.; Schoenfeld, D.; Thompson, B.T.; Wheeler, A. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N. Engl. J. Med. 2000, 342, 1301–1308.
  10. Amato, M.B.; Meade, M.O.; Slutsky, A.S.; Brochard, L.; Costa, E.L.; Schoenfeld, D.A.; Stewart, T.E.; Briel, M.; Talmor, D.; Mercat, A.; et al. Driving pressure and survival in the acute respiratory distress syndrome. N. Engl. J. Med. 2015, 372, 747–755.
  11. Brower, R.G.; Lanken, P.N.; MacIntyre, N.; Matthay, M.A.; Morris, A.; Ancukiewicz, M.; Schoenfeld, D.; Thompson, B.T.; National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome. N. Engl. J. Med. 2004, 351, 327–336.
  12. Gattinoni, L.; Chiumello, D.; Caironi, P.; Busana, M.; Romitti, F.; Brazzi, L.; Camporota, L. COVID-19 pneumonia: Different respiratory treatments for different phenotypes? Intensive Care Med. 2020, 46, 1099–1102.
  13. Tsolaki, V.; Siempos, I.; Magira, E.; Kokkoris, S.; Zakynthinos, G.E.; Zakynthinos, S. PEEP levels in COVID-19 pneumonia. Crit. Care 2020, 24, 303.
  14. Grasselli, G.; Tonetti, T.; Protti, A.; Langer, T.; Girardis, M.; Bellani, G.; Laffey, J.; Carrafiello, G.; Carsana, L.; Rizzuto, C.; et al. Pathophysiology of COVID-19-associated acute respiratory distress syndrome: A multicentre prospective observational study. Lancet Respir. Med. 2020, 8, 1201–1208.
  15. Langer, T.; Brioni, M.; Guzzardella, A.; Carlesso, E.; Cabrini, L.; Castelli, G.; Dalla Corte, F.; De Robertis, E.; Favarato, M.; Forastieri, A.; et al. PRONA-COVID Group. Prone position in intubated, mechanically ventilated patients with COVID-19: A multi-centric study of more than 1000 patients. Crit. Care 2021, 25, 128.
  16. Angus, D.C.; Derde, L.; Al-Beidh, F.; Annane, D.; Arabi, Y.; Beane, A.; van Bentum-Puijk, W.; Berry, L.; Bhimani, Z.; Bonten, M.; et al. Effect of Hydrocortisone on Mortality and Organ Support in Patients with Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial. JAMA 2020, 324, 1317–1329.
  17. RECOVERY Collaborative Group. Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): A randomised, controlled, open-label, platform trial. Lancet 2021, 397, 1637–1645.
  18. REMAP-CAP Investigators; Gordon, A.C.; Mouncey, P.R.; Al-Beidh, F.; Rowan, K.M.; Nichol, A.D.; Arabi, Y.M.; Annane, D.; Beane, A.; van Bentum-Puijk, W.; et al. Interleukin-6 Receptor Antagonists in Critically Ill Patients with COVID-19. N. Engl. J. Med. 2021, 384, 1491–1502.
  19. Slutsky, A.S. Neuromuscular blocking agents in ARDS. N. Engl. J. Med. 2010, 363, 1176–1180.
  20. National Heart, Lung, and Blood Institute PETAL Clinical Trials Network; Moss, M.; Huang, D.T.; Brower, R.G.; Ferguson, N.D.; Ginde, A.A.; Gong, M.N.; Grissom, C.K.; Gundel, S.; Hayden, D.; et al. Early Neuromuscular Blockade in the Acute Respiratory Distress Syndrome. N. Engl. J. Med. 2019, 380, 1997–2008.
  21. Papazian, L.; Forel, J.M.; Gacouin, A.; Penot-Ragon, C.; Perrin, G.; Loundou, A.; Jaber, S.; Arnal, J.M.; Perez, D.; Seghboyan, J.M.; et al. ACURASYS Study Investigators. Neuromuscular blockers in early acute respiratory distress syndrome. N. Engl. J. Med. 2010, 363, 1107–1116.
  22. Guervilly, C.; Bisbal, M.; Forel, J.M.; Mechati, M.; Lehingue, S.; Bourenne, J.; Perrin, G.; Rambaud, R.; Adda, M.; Hraiech, S.; et al. Effects of neuromuscular blockers on transpulmonary pressures in moderate to severe acute respiratory distress syndrome. Intensive Care Med. 2017, 43, 408–418.
  23. Yoshida, T.; Nakahashi, S.; Nakamura, M.A.M.; Koyama, Y.; Roldan, R.; Torsani, V.; De Santis, R.R.; Gomes, S.; Uchiyama, A.; Amato, M.B.P.; et al. Volume-controlled Ventilation Does Not Prevent Injurious Inflation during Spontaneous Effort. Am. J. Respir. Crit. Care Med. 2017, 196, 590–601.
  24. Yoshida, T.; Torsani, V.; Gomes, S.; De Santis, R.R.; Beraldo, M.A.; Costa, E.L.; Tucci, M.R.; Zin, W.A.; Kavanagh, B.P.; Amato, M.B. Spontaneous effort causes occult pendelluft during mechanical ventilation. Am. J. Respir. Crit. Care Med. 2013, 188, 1420–1427.
  25. Beitler, J.R.; Sands, S.A.; Loring, S.H.; Owens, R.L.; Malhotra, A.; Spragg, R.G.; Matthay, M.A.; Thompson, B.T.; Talmor, D. Quantifying unintended exposure to high tidal volumes from breath stacking dyssynchrony in ARDS: The BREATHE criteria. Intensive Care Med. 2016, 42, 1427–1436.
  26. Kallet, R.H.; Alonso, J.A.; Luce, J.M.; Matthay, M.A. Exacerbation of acute pulmonary edema during assisted mechanical ventilation using a low-tidal volume, lung-protective ventilator strategy. Chest 1999, 116, 1826–1832.
  27. Kress, J.P.; Pohlman, A.S.; O’Connor, M.F.; Hall, J.B. Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. N. Engl. J. Med. 2000, 342, 1471–1477.
  28. Olsen, H.T.; Nedergaard, H.K.; Strøm, T.; Oxlund, J.; Wian, K.A.; Ytrebø, L.M.; Kroken, B.A.; Chew, M.; Korkmaz, S.; Lauridsen, J.T.; et al. Nonsedation or Light Sedation in Critically Ill, Mechanically Ventilated Patients. N. Engl. J. Med. 2020, 382, 1103–1111.
  29. Marik, P.E.; Kaufman, D. The effects of neuromuscular paralysis on systemic and splanchnic oxygen utilization in mechanically ventilated patients. Chest 1996, 109, 1038–1042.
  30. Forel, J.M.; Roch, A.; Marin, V.; Michelet, P.; Demory, D.; Blache, J.L.; Perrin, G.; Gainnier, M.; Bongrand, P.; Papazian, L. Neuromuscular blocking agents decrease inflammatory response in patients presenting with acute respiratory distress syndrome. Crit. Care Med. 2006, 34, 2749–2757.
  31. Sottile, P.D.; Albers, D.; Moss, M.M. Neuromuscular blockade is associated with the attenuation of biomarkers of epithelial and endothelial injury in patients with moderate-to-severe acute respiratory distress syndrome. Crit. Care 2018, 22, 63.
  32. Fanelli, V.; Morita, Y.; Cappello, P.; Ghazarian, M.; Sugumar, B.; Delsedime, L.; Batt, J.; Ranieri, V.M.; Zhang, H.; Slutsky, A.S. Neuromuscular Blocking Agent Cisatracurium Attenuates Lung Injury by Inhibition of Nicotinic Acetylcholine Receptor-α1. Anesthesiology 2016, 124, 132–140.
  33. Lyu, G.; Wang, X.; Jiang, W.; Cai, T.; Zhang, Y. Clinical study of early use of neuromuscular blocking agents in patients with severe sepsis and acute respiratory distress syndrome. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2014, 26, 325–329. (In Chinese)
  34. Gainnier, M.; Roch, A.; Forel, J.M.; Thirion, X.; Arnal, J.M.; Donati, S.; Papazian, L. Effect of neuromuscular blocking agents on gas exchange in patients presenting with acute respiratory distress syndrome. Crit. Care Med. 2004, 32, 113–119.
  35. Rao, Z.L.J.; Ma, Y.; Li, X.; Xue, J.; Tian, L.; Zhou, W.; Kuang, Y. To retain spontaneous breathing or eliminate spontaneous breathing with neuromuscular blockers in acute respiratory distress syndrome patients? Chin. Crit. Care Med. 2016, 28, 973–977.
  36. Courcelle, R.; Gaudry, S.; Serck, N.; Blonz, G.; Lascarrou, J.B.; Grimaldi, D.; On Behalf the COVADIS Study Group. Neuromuscular blocking agents (NMBA) for COVID-19 acute respiratory distress syndrome: A multicenter observational study. Crit. Care 2020, 24, 446.
  37. Lee, B.Y.; Lee, S.I.; Baek, M.S.; Baek, A.R.; Na, Y.S.; Kim, J.H.; Seong, G.M.; Kim, W.Y. Lower Driving Pressure and Neuromuscular Blocker Use Are Associated with Decreased Mortality in Patients With COVID-19 ARDS. Respir. Care 2022, 67, 216–226.
  38. Alhazzani, W.; Møller, M.H.; Arabi, Y.M.; Loeb, M.; Gong, M.N.; Fan, E.; Oczkowski, S.; Levy, M.M.; Derde, L.; Dzierba, A.; et al. Surviving Sepsis Campaign: Guidelines on the management of critically ill adults with Coronavirus Disease 2019 (COVID-19). Intensive Care Med. 2020, 46, 854–887.
  39. Núñez-Seisdedos, M.N.; Lázaro-Navas, I.; López-González, L.; López-Aguilera, L. Intensive Care Unit-Acquired Weakness and Hospital Functional Mobility Outcomes Following Invasive Mechanical Ventilation in Patients with COVID-19: A Single-Centre Prospective Cohort Study. J. Intensive Care Med. 2022, 37, 1005–1014.
  40. Huang, D.T.; Angus, D.C.; Moss, M.; Thompson, B.T.; Ferguson, N.D.; Ginde, A.; Gong, M.N.; Gundel, S.; Hayden, D.L.; Hite, R.D.; 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.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
Upload a video for this entry
Information
Subjects: Critical Care Medicine
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Vasiliki Tsolaki
,
George E. Zakynthinos
,
Maria-Eirini Papadonta
,
Fotini Bardaka
,
George Fotakopoulos
,
Ioannis Pantazopoulos
,
Demosthenes Makris
,
Epaminondas Zakynthinos
View Times: 503
Revisions: 2 times (View History)
Update Date: 18 Oct 2022
Table of Contents
    1000/1000
    Hot Most Recent
    ScholarVision Creations
    Feedback