scholarly journals Epidural morphine in COVID ARDS patients with high respiratory drive: a structured summary of a study protocol for a randomised controlled trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Swagata Tripathy ◽  
P. Bhaskar Rao
Keyword(s):  
Epidural Catheter ◽  
Epidural Morphine ◽  
Intervention Group ◽  
Respiratory Drive ◽  
Invasive Ventilation ◽  
Exclusion Criteria ◽  
Non Invasive ◽  
Non Invasive Ventilation ◽  
Full Protocol ◽  
Allocation Ratio

Abstract Objectives We aim to study the effect of epidural morphine as a means to reduce high respiratory drive in COVID 19 patients on non-invasive ventilation (NIV)—primary end point—and to study its effect on respiratory parameters, subjective patient comfort, rates of endotracheal intubation, duration of mechanical ventilation and mortality. Trial design Parallel group, randomised, double blind, single centre placebo control trial. Allocation ratio 1:1, superiority trial Participants Trial site and population—COVID ICU patients in the All India Institute of Medical Sciences (AIIMS) Bhubaneswar, Odisha, India Inclusion and exclusion criteria Inclusion criteria Adult patients on NIV with COVID-19 Exclusion criteria Metabolic acidosis HCO3-< 16 and pH < 7.2. Severe hypoxemia warranting cessation of NIV and intubation, non-acceptance of NIV and proven sepsis. Technical difficulty for epidural catheterization, coagulation abnormalities, low respiratory drive and EOL orders. Sources or methods of recruitment—daily discussion at 8 am of new admissions to COVID ICU on NIV—consenting adult patients with COVID19 on NIV and high respiratory drive; not meeting exclusion criteria will be recruited for the trial and randomised. Intervention and comparator Patients of both groups will be turned to a lateral or sitting position (as comfortable), and an injection of local anaesthetic be given at lumbar 2–3/3–4 space. In the intervention group, an epidural catheter will be inserted using aseptic technique and fixed to the skin. The control group will have a sham catheter fixed exactly like in the intervention group, but not entering the epidural space. The intervention group will be administered injection morphine sulphate once every 18–24 h into the epidural space. The doses will be escalated daily (5–10 mg), titrated to effect: escalation limited by hypoventilation resulting in respiratory acidosis (pH < 7.2). The intervention will continue for a minimum of 2 doses and a maximum of 5 doses (96 h) of morphine. It will be stopped if the epidural catheter gets dislodged before the second dose or the patient is weaned off non-invasive ventilation to high flow mask for a continuous period of 24 h or requires endotracheal intubation. The patient will be followed up till death or 28 days after ICU discharge. Main outcomes Primary outcome—diaphragm thickening index fraction (average of minimum 3 readings) Secondary outcomes—ventilator parameters, sedation and pain scores, subjective comfort and dyspnoea scores, time to intubation, length of stay on NIV and 28-day mortality Timing of outcome assessment—every 8th hour assessment for 24 h after the last dose of epidural morphine or 120 h whichever is greater Randomisation A central random number list will be kept with the study research assistant. She will randomise according to the numbers available in the list using an allocation ratio of 1:1. An opaque sealed envelope concealing the allotted randomisation code will be dispatched to the ICU team. Blinding (masking) The assessor, patient, nurses and physicians will be blind to group allocation. One member of the team not involved in research will administer the intervention. Numbers to be randomised (sample size) Twenty-five patients per group; 50 patients total Trial status Protocol version 1. Not recruiting yet. Recruitment to begin by 24 July 2021 and end by 31 August 2022 Trial registration Central Trials Registry India CTRI CTRI/2021/07/035093. Registered on 23 July 2021. Prospectively registered Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol

The Effect of Non-Invasive Mechanical Ventilation on Respiratory and Inflammatory Parameters in Patients with Chronic Obstructive Pulmonary Disease

2021 ◽  
Author(s):  
Mohammad Hashemian ◽  
Atefeh Fakharian ◽  
Reyhaneh Zahiri ◽  
Esmaeil Mortaz ◽  
Mohammad Reza Masjedi
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Invasive Mechanical Ventilation ◽  
Intervention Group ◽  
Control Group ◽  
Chronic Obstructive ◽  
Invasive Ventilation ◽  
Obstructive Pulmonary Disease ◽  
Non Invasive ◽  
The Third ◽  
Non Invasive Ventilation

Background: Chronic Obstructive Pulmonary Disease (COPD) is an airway obstructive disease that is often caused by smoking. The disease is currently the third leading cause of death worldwide. The current therapeutic approach is based on Non-Invasive Ventilation (NIV) therapy, which can reduce mortality, the need for hospitalization in the intensive care unit, and to some extent therapeutic complications. Therefore, this study was performed to determine the effect of non-invasive ventilation along with routine treatments on respiratory markers, inflammation, and clinical status of patients with COPD. Methods: A total of 30 patients with COPD referred to Masih Daneshvari Hospital were divided into control and intervention groups. In the intervention group, 15 patients underwent non-invasive ventilation in addition to the usual treatments, and in the control group, the patients underwent only the usual treatments. After completing the mMRC (Modified Medical Research Council) questionnaire and evaluating FEV1 (Forced Expiratory Value in one score), 5 ml of blood samples were taken from these patients at the beginning of the study, on the seventh to tenth day, and also in the third month, and the results of this evaluation were compared between the two groups. Results: Based on the results of this study, the mMRC score of the intervention group was significantly lower than the control group in the first week (p=0.043) and three months after treatment (p=0.049). However, indices such as FEV1, and IL-8(Interleukin-8) did not change significantly in both groups. Conclusion: The use of non-invasive mechanical ventilation along with standard treatments can play a relative role in improving patient outcomes.

scholarly journals Recombinant human C1 esterase inhibitor (conestat alfa) in the prevention of severe SARS-CoV-2 infection in hospitalized patients with COVID-19: A structured summary of a study protocol for a randomized, parallel-group, open-label, multi-center pilot trial (PROTECT-COVID-19)

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Pascal Urwyler ◽  
Panteleimon Charitos ◽  
Stephan Moser ◽  
Ingmar A. F. M. Heijnen ◽  
Marten Trendelenburg ◽  
...  
Keyword(s):  
Informed Consent ◽  
Ordinal Scale ◽  
Invasive Ventilation ◽  
Open Label ◽  
Non Invasive ◽  
C1 Esterase Inhibitor ◽  
Non Invasive Ventilation ◽  
Parallel Group ◽  
Full Protocol ◽  
Esterase Inhibitor

Abstract Objectives Conestat alfa, a recombinant human C1 esterase inhibitor, is a multi-target inhibitor of inflammatory cascades including the complement, the kinin-kallikrein and the contact activation system. The study objective is to investigate the efficacy and safety of conestat alfa in improving disease severity and short-term outcome in COVID-19 patients with pulmonary disease. Trial design This study is an investigator-initiated, randomized (2:1 ratio), open-label, parallel-group, controlled, multi-center, phase 2a clinical trial. Participants This trial is conducted in 3 hospitals in Switzerland, 1 hospital in Brazil and 1 hospital in Mexico (academic and non-academic). All patients with confirmed SARS-CoV-2 infection requiring hospitalization for at least 3 calendar days for severe COVID-19 will be screened for study eligibility. Inclusion criteria: - Signed informed consent - Age 18-85 years - Evidence of pulmonary involvement on CT scan or X-ray of the chest - Duration of symptoms associated with COVID-19 ≤ 10 days - At least one of the following risk factors for progression to mechanical ventilation on the day of enrolment: 1) Arterial hypertension 2) ≥ 50 years 3) Obesity (BMI ≥ 30 kg/m2) 4) History of cardiovascular disease 5) Chronic pulmonary disease 6) Chronic renal disease 7) C-reactive protein > 35mg/L 8) Oxygen saturation at rest of ≤ 94% when breathing ambient air Exclusion criteria: - Incapacity or inability to provide informed consent - Contraindications to the class of drugs under investigation (C1 esterase inhibitor) - Treatment with tocilizumab or another IL-6R or IL-6 inhibitor before enrolment - History or suspicion of allergy to rabbits - Pregnancy or breast feeding - Active or anticipated treatment with any other complement inhibitor - Liver cirrhosis (any Child-Pugh score) - Admission to an ICU on the day or anticipated within the next 24 hours of enrolment - Invasive or non-invasive ventilation - Participation in another study with any investigational drug within the 30 days prior to enrolment - Enrolment of the study investigators, their family members, employees and other closely related or dependent persons Intervention and comparator Patients randomized to the experimental arm will receive conestat alfa in addition to standard of care (SOC). Conestat alfa (8400 U followed by 4200 U every 8 hours) will be administered as a slow intravenous injection (5-10 minutes) over a 72-hour period (i.e. 9 administrations in total). The first conestat alfa treatment will be administered on the day of enrolment. The control group will receive SOC only. SOC treatment will be administered according to local institutional guidelines, including supplemental oxygen, antibiotics, corticosteroids, remdesivir, and anticoagulation. Main outcomes The primary endpoint of this trial is disease severity on day 7 after enrolment assessed by an adapted WHO Ordinal Scale for Clinical Improvement (score 0 will be omitted and score 6 and 7 will be combined) from 1 (no limitation of activities) to 7 (death). Secondary outcomes include (i) the time to clinical improvement (time from randomization to an improvement of two points on the WHO ordinal scale or discharge from hospital) within 14 days after enrolment, (ii) the proportion of participants alive and not having required invasive or non-invasive ventilation at 14 days after enrolment and (iii) the proportion of subjects without an acute lung injury (defined by PaO2/FiO2 ratio of ≤300mmHg) within 14 days after enrolment. Exploratory outcomes include virological clearance, C1 esterase inhibitor pharmacokinetics and changes in routine laboratory parameters and inflammatory proteins. Randomisation Subjects will be randomised in a 2:1 ratio to treatment with conestat alfa in addition to SOC or SOC only. Randomization is performed via an interactive web response system (SecuTrial®). Blinding (masking) In this open-label trial, participants, caregivers and outcome assessors are not blinded to group assignment. Numbers to be randomised (sample size) We will randomise approximately 120 individuals (80 in the active treatment arm, 40 in the SOC group). Two interim analyses after 40 and 80 patients are planned according to the Pocock adjusted levels αp = 0.0221. The results of the interim analysis will allow adjustment of the sample size (Lehmacher, Wassmer, 1999). Trial Status PROTECT-COVID-19 protocol version 3.0 (July 07 2020). Participant recruitment started on July 30 2020 in one center (Basel, Switzerland, first participant included on August 06 2020). In four of five study centers patients are actively recruited. Participation of the fifth study center (Mexico) is anticipated by mid December 2020. Completion of trial recruitment depends on the development of the SARS-CoV-2 pandemic. Trial registration Clinicaltrials.gov, number: NCT04414631, registered on 4 June 2020 Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

scholarly journals Sedation in non-invasive ventilation: do we know what to do (and why)?

2014 ◽  
Vol 9 ◽  
Author(s):  
Dan Longrois ◽  
Giorgio Conti ◽  
Jean Mantz ◽  
Andreas Faltlhauser ◽  
Riku Aantaa ◽  
...  
Keyword(s):  
Best Practice ◽  
Standards Of Care ◽  
Respiratory Drive ◽  
Invasive Ventilation ◽  
Missed Opportunities ◽  
Organizational Conditions ◽  
Non Invasive ◽  
Ideal Agent ◽  
Non Invasive Ventilation ◽  
As Effects

This review examines some of the issues encountered in the use of sedation in patients receiving respiratory support from non-invasive ventilation (NIV). This is an area of critical and intensive care medicine where there are limited (if any) robust data to guide the development of best practice and where local custom appears to exert a strong influence on patterns of care. We examine aspects of sedation for NIV where the current lack of structure may be contributing to missed opportunities to improve standards of care and examine the existing sedative armamentarium. No single sedative agent is currently available that fulfils the criteria for an ideal agent but we offer some observations on the relative merits of different agents as they relate to considerations such as effects on respiratory drive and timing, and airways patency. The significance of agitation and delirium and the affective aspect(s) of dyspnoea are also considered.We outline an agenda for placing the use of sedation in NIV on a more systematic footing, including clearly expressed criteria and conditions for terminating NIV and structural and organizational conditions for prospective multicentre trials.

Non-invasive ventilation in palliative care: a systematic review

2020 ◽  
Vol 110 (6) ◽  
Author(s):  
Teresa Diaz de Teran ◽  
Elena Barbagelata ◽  
Catia Cilloniz ◽  
Antonello Nicolini ◽  
Tommaso Perazzo ◽  
...  
Keyword(s):  
Systematic Review ◽  
Palliative Care ◽  
Invasive Ventilation ◽  
Non Invasive ◽  
Non Invasive Ventilation
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