scholarly journals Eculizumab in patients with severe coronavirus disease 2019 (COVID-19) requiring continuous positive airway pressure ventilator support: Retrospective cohort study

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0261113
Author(s):  
Piero Ruggenenti ◽  
Fabiano Di Marco ◽  
Monica Cortinovis ◽  
Luca Lorini ◽  
Silvia Sala ◽  
...  
Keyword(s):  
Continuous Positive Airway Pressure ◽  
Respiratory Rate ◽  
Airway Pressure ◽  
Positive Airway Pressure ◽  
Ex Vivo ◽  
Small Sample ◽  
Chronic Complications ◽  
Baseline Serum ◽  
Ventilator Support ◽  
Lung Dysfunction

Background Complement activation contributes to lung dysfunction in coronavirus disease 2019 (COVID-19). We assessed whether C5 blockade with eculizumab could improve disease outcome. Methods In this single-centre, academic, unblinded study two 900 mg eculizumab doses were added-on standard therapy in ten COVID-19 patients admitted from February 2020 to April 2020 and receiving Continuous-Positive-Airway-Pressure (CPAP) ventilator support from ≤24 hours. We compared their outcomes with those of 65 contemporary similar controls. Primary outcome was respiratory rate at one week of ventilator support. Secondary outcomes included the combined endpoint of mortality and discharge with chronic complications. Results Baseline characteristics of eculizumab-treated patients and controls were similar. At baseline, sC5b-9 levels, ex vivo C5b-9 and thrombi deposition were increased. Ex vivo tests normalised in eculizumab-treated patients, but not in controls. In eculizumab-treated patients respiratory rate decreased from 26.8±7.3 breaths/min at baseline to 20.3±3.8 and 18.0±4.8 breaths/min at one and two weeks, respectively (p<0.05 for both), but did not change in controls. Between-group changes differed significantly at both time-points (p<0.01). Changes in respiratory rate correlated with concomitant changes in ex vivo C5b-9 deposits at one (rs = 0.706, p = 0.010) and two (rs = 0.751, p = 0.032) weeks. Over a median (IQR) period of 47.0 (14.0–121.0) days, four eculizumab-treated patients died or had chronic complications versus 52 controls [HRCrude (95% CI): 0.26 (0.09–0.72), p = 0.010]. Between-group difference was significant even after adjustment for age, sex and baseline serum creatinine [HRAdjusted (95% CI): 0.30 (0.10–0.84), p = 0.023]. Six patients and 13 controls were discharged without complications [HRCrude (95% CI): 2.88 (1.08–7.70), p = 0.035]. Eculizumab was tolerated well. The main study limitations were the relatively small sample size and the non-randomised design. Conclusions In patients with severe COVID-19, eculizumab safely improved respiratory dysfunction and decreased the combined endpoint of mortality and discharge with chronic complications. Findings need confirmation in randomised controlled trials.

scholarly journals Positive role of continuous positive airway pressure for intensive care unit patients with severe hypoxaemic respiratory failure due to COVID-19 pneumonia: A single centre experience

2020 ◽  
pp. 175114372097154
Author(s):  
Dariusz R Wozniak ◽  
Antonio Rubino ◽  
Aileen LW Tan ◽  
Nicola L Jones ◽  
Stephen T Webb ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Respiratory Failure ◽  
Continuous Positive Airway Pressure ◽  
Airway Pressure ◽  
Positive Airway Pressure ◽  
Ventilatory Support ◽  
Small Sample ◽  
Pulmonary Angiogram ◽  
D Dimer

Objectives Continuous positive airway pressure (CPAP) may be a useful treatment strategy for patients with severe COVID-19 pneumonia but its effectiveness in preventing mechanical ventilation is unknown. We aimed to evaluate the outcomes of COVID-19 patients treated with CPAP and determine predictors of CPAP response. Design This was a retrospective observational cohort study. Setting The study took place in the intensive care unit (ICU) at Royal Papworth Hospital (RPH) in Cambridge, UK. Patients We included all consecutive patients with confirmed COVID-19 pneumonia who were transferred from neighbouring hospitals between 14th March and 6th May, 2020 for consideration of ventilatory support. Intervention We instituted the use of CPAP for all patients who arrived in RPH not intubated and were not making satisfactory progress on supplemental oxygen alone. Measurements and main results Of 33 self-ventilating patients included in this study, 22 (66.7%) were male and the mean age was 54 ± 13.23 patients received CPAP. They were more hypoxaemic than those treated with oxygen alone (PaO2/FiO2 ratio; 84.3 ± 19.0 vs 170.0 ± 46.0 mmHg, p = 0.001). There was a significant improvement in PaO2/FiO2 ratio 1–2 hours after CPAP initiation (167.4 ± 49.0 from 84.3 ± 19.0 mmHg, p = 0.001). 14 (61%) patients responded to CPAP and 9 required intubation. There was no difference between these two groups in terms of the severity of baseline hypoxaemia (PaO2/FiO2 ratio; 84.5 ± 16.0 vs 83.9 ± 23.0 mmHg, p = 0.94) but CPAP responders had significantly lower C-reactive protein (CRP) (176 ± 83 vs 274 ± 63 mg/L, p = 0.007), interleukin-6 (IL-6) (30 ± 47 vs 139 ± 148 pg/mL, p = 0.037), and D-dimer (321 ± 267 vs 941 + 1990 ng/mL, p = 0.003). CT pulmonary angiogram was performed in 6 out of 9 intubated patients and demonstrated pulmonary emboli in 5 of them. All patients were discharged from ICU and there were no fatalities. Conclusions In this cohort, CPAP was an effective treatment modality to improve hypoxaemia and prevent invasive ventilation in a substantial proportion of patients with severe respiratory failure. Accepting the small sample size, we also found raised biomarkers of inflammation (CRP and IL-6) and coagulopathy (D-Dimer) to be more useful predictors of CPAP responsiveness than the severity of hypoxaemia, and could help to guide intubation decisions in this clinical setting.

Effects of incremental levels of continuous positive airway pressure on cerebral blood flow velocity in healthy adult humans

2003 ◽  
Vol 104 (6) ◽  
pp. 633-639 ◽  
Author(s):  
R. SCALA ◽  
P. M. TURKINGTON ◽  
P. WANKLYN ◽  
J. BAMFORD ◽  
M. W. ELLIOTT
Keyword(s):  
Heart Rate ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Continuous Positive Airway Pressure ◽  
Respiratory Rate ◽  
Blood Flow Velocity ◽  
Airway Pressure ◽  
Positive Airway Pressure ◽  
Cerebral Blood Flow Velocity ◽  
Cerebrovascular Resistance

Sleep disordered breathing is common in patients with cerebrovascular disease, and could exacerbate the cerebral damage in acute stroke. Data about the effects of continuous positive airway pressure (CPAP) upon cerebral perfusion are conflicting. We investigated whether increasing levels of CPAP may affect cerebral haemodynamics, assessed by transcranial Doppler (TCD) in normal humans. A group of 25 healthy young volunteers were evaluated before (CPAP0-pre), during (CPAP5, CPAP10 and CPAP15, denoting CPAP at 5, 10 and 15 cmH2O respectively) and after (CPAP0-post) application of incremental levels of CPAP delivered through a mouthpiece. The mean cerebral blood flow velocity (CBFV) and the pulsatility index (PI; an indirect measure of cerebrovascular resistance) in the middle cerebral artery were measured with TCD. Respiratory rate, heart rate, end-tidal carbon dioxide pressure (PETCO2), transcutaneous haemoglobin oxygen saturation (SpO2), mean arterial blood pressure and anxiety score were also recorded. Compared with CPAP0-pre, CBFV was significantly decreased as higher levels of CPAP were applied (P<0.0001). CPAP15 increased PI (P<0.05), PETCO2 was reduced by CPAP10 and CPAP15 (P<0.0001), and anxiety score and SpO2 increased at all levels of CPAP (P<0.05). Heart rate, respiratory rate and mean arterial pressure did not change. The decrease in CBFV was correlated with the fall in PETCO2 (CPAP15) and the increase in PI (CPAP10, CPAP15) (P<0.05). In conclusion, even low levels of CPAP delivered through a mouthpiece in awake, young volunteers led to a decrease in CBFV, measured by TCD. This fall in CBFV was associated with hypocapnia and with an increase in both cerebrovascular resistance and anxiety due to breathing against positive pressure. As the negative consequences of a fall in CBFV may outweigh the therapeutic effects of CPAP in the post-stroke setting, further studies of the cerebrovascular effects of CPAP with different interfaces in elderly patients with and without stroke are needed before intervention trials can be performed safely.

scholarly journals Influence of nasal CPAP on cardiorespiratory control in healthy neonate

2019 ◽  
Vol 127 (5) ◽  
pp. 1370-1385
Author(s):  
Sally Al-Omar ◽  
Virginie Le Rolle ◽  
Patrick Pladys ◽  
Nathalie Samson ◽  
Alfredo Hernandez ◽  
...  
Keyword(s):  
Heart Rate ◽  
Signal Processing ◽  
Heart Rate Variability ◽  
Continuous Positive Airway Pressure ◽  
Lung Disease ◽  
Respiratory Rate ◽  
Airway Pressure ◽  
Positive Airway Pressure ◽  
Efferent Activity ◽  
Respiratory Rate Variability

The present study aimed to further unravel the effects of nasal continuous positive airway pressure (nCPAP) on the cardiovascular and respiratory systems in the neonatal period. Six-hour polysomnographic recordings were first performed in seven healthy newborn lambs, aged 2–3 days, without and with nCPAP application at 6 cmH2O (nCPAP-6), in randomized order. The effects of nCPAP-6 on heart rate variability, respiratory rate variability, and cardiorespiratory interrelations were analyzed using a semiautomatic signal processing approach applied to ECG and respiration recordings. Thereafter, a cardiorespiratory mathematical model was adapted to the experimental conditions to gain further physiological interpretation and to simulate higher nCPAP levels (8 and 10 cmH2O). Results from the signal processing approach suggest that nCPAP-6 applied in newborns with healthy lungs: 1) increases heart rate and decreases the time and frequency domain indices of heart rate variability, especially those representing parasympathetic activity, while increasing the complexity of the RR-interval time series; 2) prolongs the respiratory cycle and expiration duration and decreases respiratory rate variability; and 3) slightly impairs cardiorespiratory interrelations. Model-based analysis revealed that nCPAP-6 increases the heart rate and decreases respiratory sinus arrhythmia amplitude, in association with a reduced parasympathetic efferent activity. These results were accentuated when simulating an increased CPAP level. Overall, our results provide a further understanding of the effects of nCPAP in neonates, in the absence of lung disease. NEW & NOTEWORTHY Application of nasal continuous positive airway pressure (CPAP) at 6 cmH2O, a level very frequently used in newborns, alters heart and respiratory rate variability, as well as cardiorespiratory interrelations in a full-term newborn model without lung disease. Moreover, whereas nasal CPAP at 6 cmH2O decreases parasympathetic efferent activity, there is no change in sympathetic efferent activity.

Continuous Positive Airway Pressure (CPAP) Therapy for the Treatment of Hypernasality: A Single Case Study

2014 ◽  
Vol 24 (2) ◽  
pp. 48-58 ◽  
Author(s):  
Lakshmi Kollara ◽  
Graham Schenck ◽  
Jamie Perry
Keyword(s):  
Continuous Positive Airway Pressure ◽  
Airway Pressure ◽  
Positive Airway Pressure ◽  
Single Case ◽  
Treatment Method ◽  
Post Treatment ◽  
Subjective Perception ◽  
Cpap Therapy ◽  
Long Term Follow Up

Studies have investigated the applications of Continuous Positive Airway Pressure (CPAP) therapy in the treatment of hypernasality due to velopharyngeal dysfunction (VPD; Cahill et al., 2004; Kuehn, 1991; Kuehn, Moon, & Folkins, 1993; Kuehn et al., 2002). The purpose of this study was to examine the effectiveness of CPAP therapy to reduce hypernasality in a female subject, post-traumatic brain injury (TBI) and pharyngeal flap, who presented with signs of VPD including persistent hypernasality. Improvements in mean velopharyngeal orifice size, subjective perception of hypernasality, and overall intelligibility were observed from the baseline to 8-week post-treatment assessment intervals. Additional long-term assessments completed at 2, 3, and 4 months post-treatment indicated decreases in immediate post-treatment improvements. Results from the present study suggest that CPAP is a safe, non-invasive, and relatively conservative treatment method for reduction of hypernasality in selected patients with TBI. More stringent long-term follow up may indicate the need for repeated CPAP treatment to maintain results.

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