Need For Invasive Ventilation Research Articles

The Impact of Antenatal Corticosteroids on the Metabolome of Preterm Newborns: An Untargeted Approach

We analyzed and compared variations in the urinary metabolome, as well as postnatal clinical outcomes among preterm infants, based on the timing of antenatal corticosteroid (ACS) administration in response to preterm labor onset in their mothers. This was a prospective observational study held in the Neonatal Intensive Care Unit, Department of Woman’s and Child’s Health, Padova University Hospital (Italy). A urine sample was obtained from each patient within 24 h of birth; Mass Spectrometry-based untargeted metabolomics analysis was then conducted. We searched for any significant disparities in the metabolomic profile of preterm newborns subjected to antenatal corticosteroid (ACS) treatment at varying timings; their correlation with clinical outcomes were also evaluated. The group receiving ACS within the optimal time window (1–7 days before delivery) exhibited elevated levels of cysteine, N-acetylglutamine, propionyl carnitine and 5-hydroxyindolacetic acid, coupled with a decrease in pipecolic acid. Clinically, this group demonstrated a reduced need for invasive ventilation (p = 0.04). In conclusion, metabolomics analysis identified several metabolites that discriminated preterm infants whose mothers received ACS within the recommended time window. Elevated levels of cysteine and 5-Hydroxyindoleacetic acid, metabolites characterized by antioxidant and anti-inflammatory properties, were observed in these infants. This metabolic profile correlated with improved respiratory outcomes, as evidenced by a reduced necessity for invasive ventilation at birth.

The effect of NHFOV on hemodynamics in mild and moderately preterm neonates: a randomized clinical trial.

The aim of this study is to study cardio-respiratory effects of nasal high-frequency oscillatory ventilation (NHFOV) vs. NCPAP as an initial mode of ventilation in moderate-late-preterm infants. A randomized controlled trial was conducted in NICU of Alexandria University Maternity Hospital (AUMH). One-hundred late-moderate-preterm infants were randomly assigned to either NHFOV-group (n = 50) or NCPAP-group (n = 50). For both groups, functional echocardiography was performed in the first 24h to detect hemodynamic changes and respiratory outcome was monitored throughout the hospital stay. The main outcomes were hemodynamic measurements and myocardial function using functional echocardiography of those infants along with the respiratory outcome and complications. Kaplan-Meier survival plot was used representing time course of NCPAP and NHFOV failure. Left ventricular output values were not significantly different in both groups with median 202ml/kg /min and IQR (176-275) in NCPAP-group and 226ml/kg/min with IQR (181-286) in NHFOV group. Nevertheless, ejection fraction and fractional shortening were significantly higher in NHFOV-group with P 0.001. The time to weaning, the time to reach 30%-FIO2, the need for invasive ventilation, oxygen support duration, and maximal-FIO2 were significantly more in NCAPAP group. Conclusion: NHFOV is an effective and promising tool of non-invasive-ventilation which can be used as a primary modality of respiratory support in preterm infants with variable forms of respiratory distress syndrome without causing detrimental effect on hemodynamics or significant respiratory complications. Trial registration: NCT05706428 (registered on January 21, 2023). What is Known: • NHFOV might be beneficial as a secondary mode of ventilation and might have an impact on hemodynamics. What is New: • NHFOV can be used as an initial mode of ventilation with CDP beyond the reported pressure limits of CPAP without causing neither CO2 retention nor adverse hemodynamic consequences.

Tocilizumab in Severe and Critical COVID-19 Pneumonia: Streamlining the Mixed Signals

Four years since the start of the pandemic, the first lockdown in Manila happened on March 15, 2020 causing a pandemonium in the metro as the Filipinos gear up for the unexpected. As the suspected and confirmed cases grew, case numbers of unidentified patients soon became friends, relatives, and loved ones. As of May 2023 1 , there have been more than 1.3 million confirmed COVID-19 cases in Metro Manila alone with almost 14,000 deaths from severe and critical cases.
 The current knowledge about the disease as well as the explanation of its widely varied symptomatology continues to evolve. 2-4 At the center of the discussion for severe and critical COVID-19 requiring hospitalization is the hyperactivation ofthe inflammatory response resulting to simultaneous increase in multiple cytokines. 4,5 Such an inflammatory cascade results in nonspecific inflammatory reaction from damaged or dysfunctional virus-infected host cells making it difficult to identify a specific mediator of inflammatory response. 5,6 It is therefore not surprising that multiple therapeutic trials done targeting specific cytokines such as IL-6 and TNF-a have also led to mixed results. 7-10
 Since 2020, aggressive research has allowed both the development of new medications as well as repurposing of other molecules in the treatment of COVID-19. Antiviral drugs, monoclonal antibodies, IL-6R inhibitor/immune modulators, andsystemic corticosteroids have become household names. 6 IL-6, an identified key propagator of the cytokine storm in severe and critical COVID, has been the focus of the noise as mechanistically, IL-6 blockers including tocilizumab and sarilumabtheoretically disrupt the inflammatory cascade. 5-7
 If mechanistically, IL-6 blockers, particularly tocilizumab can block the inflammatory cascade, why are there mixed signals on its benefit based on real-world evidence? 7-10
 One of the largest and most recently published systematic review and meta-analysis of 15 randomized and two non- randomized clinical trials evaluating the effect of tocilizumab on the clinical outcomes of COVID-19 patients11 showed acombined cumulative risk of death in COVID-19 patients of 0.93 (RR 0.93, 95% CI 0.86 – 1.00, i 2 72.39%). The need for invasive ventilation, ICU admission was at 1.04 (RR 1.04, 95% CI 0.90 – 1.20, i 2 0.00). These figures indicate a 7% decreasedrisk of death with a 4% increased risk of ICU admission and need for invasive ventilation, again indicating mixed signals on the perceived benefit of tocilizumab. 11 Limitations in the study results compared to controlled clinical trials are probablydue to (1) heterogeneity of the patients with severe and critically ill COVID-19 patients potentially having different degrees of inflammatory activities; (2) timing of administration of tocilizumab; (3) different administrative and hospital policies inthe management of more ill patients suffering from COVID-19; and (4) presence of multiple inflammatory cytokines aside from IL-6, making it difficult to pinpoint the specific key mediator of inflammatory response on a per-patient basis.
 The local randomized controlled trial published by Amante et al.12 agree with these mixed signals from the published literature in COVID-19. In both intention-to-treat and per-protocol-analysis, there was no statistical significance and clinicalbenefit of using tocilizumab for severe and critically ill patients. Four years later, the picture is clearer now as real-world evidence coupled with carefully conducted clinical trials provide us a better understanding of the use of tocilizumab for current cases. However, back in 2020, when this mysterious respiratory illness is wreaking havoc, medications both newly developed and repurposed were offered as the medical research community was challenged by a pandemic in an unprecedented manner.
 As COVID-19 becomes endemic, the search for the cure for severe COVID-19 remains to be discovered. Given its mixed signals, shared decision making (pending confirmation in further studies) between the patient, caregiver, and the physician remains the cornerstone of management.

A retrospective observational study to determine the role of High Flow Nasal Oxygen in terms of recovery, mortality and need for invasive ventilation in COVID-19 cases

Background: Hypoxemic respiratory failure in COVID-19 is managed by conventional oxygen, High Flow Nasal Oxygen (HFNO), and invasive ventilation. Multiple studies have proven that using HFNO in the early stages of acute hypoxemia failure can lead to better outcomes and delay or avoidance of invasive ventilation. This observational study was conducted to further establish this hypothesis. Also, no difference was found in mortality rates between the usage of HFNO Conventional Oxygen Therapy. However, there are very limited studies comparing outcomes of HFNO and Invasive ventilation usage. Hence, this study was undertaken to gain insight into comparing HFNO and invasive ventilation. Materials and Methods: A retrospective data collection was performed from 06/05/2021 to 15/12/2021 after approval from the Institutional Ethics Committee. The collection was performed at MMFHA Ratna Hospital, Pune. All Indoor patient department files of positive cases of COVID first wave (2020) and second wave (2021) were screened. Reverse Transcription Polymerase Chain Reaction COVID-positive cases belonging to both genders, aged 18-100 years and where HFNO was part of management were selected, and data was extracted about socio-demographic data, clinical profile, and routine investigations advised, course of the patient in the hospital with respect to vital parameters, daily HFNO parameters, all the medications received, any other interventions if required, and the time points of taking patients off HFNO, the requirement of invasive ventilation, shifting out of Intensive Care Unit discharge, or death. Immunocompromised cancer patients and pregnant women were excluded. Outcomes were measured in terms of recovery, need for mechanical ventilation, and mortality. Results: Out of 700 cases screened, HFNO was used in 38 (5.4%) participants. The duration of HFNO ranged from less than one day to more than seven days. Of those 38, 30 (78.9%) received HFNO and 8 (21.05%) were shifted to mechanical ventilation. Out of these 30, eight (21.05%) expired on HFNO, eighteen (47.36%) were discharged, and four (10.52%) were shifted to another hospital on HFNO. All eight participants on mechanical invasive ventilation expired. Conclusions: In terms of recovery from HFNO use, discharge with a recovery rate was higher than mortality and the need for mechanical ventilation. The need for invasive mechanical ventilation was much lower in HFNO used participants (26 versus 8). All those on mechanical ventilation expired. HFNO can be a useful modality for oxygenation in COVID-19 patients. The exact role of HFNO in the trajectory of the management of hypoxemic respiratory failure due to COVID-19 needs to be defined.

Determining the Association Between the Origin of Sepsis and the Severity of Sepsis in Intensive Care Unit (ICU) Patients Using Acute Physiology and Chronic Health Evaluation (APACHE) IV.

Objective The objective of this study is to compare the outcomes of hospital mortality, the requirement of invasive ventilation, vasopressor requirement, duration of vasopressor requirement, and duration of intensive care unit (ICU) stay among the different causes of sepsis and to determine which cause of sepsis had the most severe outcomes. Methods A retrospective chart review was done in critically ill adult patients who were admitted with sepsis to the ICU from July 2017 until July 2019. Acute Physiology and Chronic Health Evaluation (APACHE) IV scores were calculated on patients admitted to ICU on day one of ICU admission. Each patient was then evaluated for outcomes of hospital mortality, need for invasive ventilation, requirement of vasopressors, duration of vasopressors, and duration of ICU stay. The outcomes were then compared between the different sources of sepsis to determine which source of sepsis had the highest severity. Results In total, 176 patients were included in the study. Ninety-three patients were admitted with respiratory sepsis, 26 patients were admitted with gastrointestinal sepsis, 31 patients were admitted with urosepsis, and 26 patients were admitted with other miscellaneous causes of sepsis. The hospital mortality was highest in the respiratory sepsis group at 32%, with a trend towards statistical significance with a P value of 0.057. ICU stay duration was highest in patients with respiratory sepsis at six days, with a statistically significant P value of < 0.001. The need for invasive ventilation was highest in patients with respiratory sepsis at 64%, with a statistically significant P value of < 0.001. The requirement of vasopressor support was highest in patients with respiratory sepsis at 47% and the duration of vasopressors was highest in both respiratory and gastrointestinal sepsis at three days, however, there was no statistical significance. Conclusion Among the different origins of sepsis, the patients with respiratory sepsis had the most severe outcomes, with the highest need for invasive ventilation and the highest ICU stay duration.

NON-pharmacological Approach Less Invasive Surfactant Administration (NONA-LISA) trial: protocol for a randomised controlled trial.

Using pre-procedure analgesia with the risk of apnoea may complicate the Less Invasive Surfactant Administration (LISA) procedure or reduce the effect of LISA. The NONA-LISA trial (ClinicalTrials.gov, NCT05609877) is a multicentre, blinded, randomised controlled trial aiming at including 324 infants born before 30 gestational weeks, meeting the criteria for surfactant treatment by LISA. Infants will be randomised to LISA after administration of fentanyl 0.5-1 mcg/kg intravenously (fentanyl group) or isotonic saline solution intravenously (saline group). All infants will receive standardised non-pharmacological comfort care before and during the LISA procedure. Additional analgesics will be provided at the clinician's discretion. The primary outcome is the need for invasive ventilation, meaning mechanical or manual ventilation via an endotracheal tube, for at least 30 min (cumulated) within 24 h of the procedure. Secondary outcomes include the modified COMFORTneo score during the procedure, bronchopulmonary dysplasia at 36 weeks, and mortality at 36 weeks. The NONA-LISA trial has the potential to provide evidence for a standardised approach to relief from discomfort in preterm infants during LISA and to reduce invasive ventilation. The results may affect future clinical practice. Pre-procedure analgesia is associated with apnoea and may complicate procedures that rely on regular spontaneous breathing, such as Less Invasive Surfactant Administration (LISA). This randomised controlled trial addresses the effect of analgesic premedication in LISA by comparing fentanyl with a placebo (isotonic saline) in infants undergoing the LISA procedure. All infants will receive standardised non-pharmacological comfort. The NONA-LISA trial has the potential to provide evidence for a standardised approach to relief from discomfort or pain in preterm infants during LISA and to reduce invasive ventilation. The results may affect future clinical practice regarding analgesic treatment associated with the LISA procedure.

A comprehensive physical functional assessment of survivors of critical care unit stay due to COVID-19.

To examine the physical function and respiratory muscle strength of patients - who recovered from critical COVID-19 - after intensive care unit discharge to the ward on Days one (D1) and seven (D7), and to investigate variables associated with functional impairment. This was a prospective cohort study of adult patients with COVID-19 who needed invasive mechanical ventilation, non-invasive ventilation or high-flow nasal cannula and were discharged from the intensive care unit to the ward. Participants were submitted to Medical Research Council sum-score, handgrip strength, maximal inspiratory pressure, maximal expiratory pressure, and short physical performance battery tests. Participants were grouped into two groups according to their need for invasive ventilation: the Invasive Mechanical Ventilation Group (IMV Group) and the Non-Invasive Mechanical Ventilation Group (Non-IMV Group). Patients in the IMV Group (n = 31) were younger and had higher Sequential Organ Failure Assessment scores than those in the Non-IMV Group (n = 33). The short physical performance battery scores (range 0 - 12) on D1 and D7 were 6.1 ± 4.3 and 7.3 ± 3.8, respectively for the Non-Invasive Mechanical Ventilation Group, and 1.3 ± 2.5 and 2.6 ± 3.7, respectively for the IMV Group. The prevalence of intensive care unit-acquired weakness on D7 was 13% for the Non-IMV Group and 72% for the IMV Group. The maximal inspiratory pressure, maximal expiratory pressure, and handgrip strength increased on D7 in both groups, but the maximal expiratory pressure and handgrip strength were still weak. Only maximal inspiratory pressure was recovered (i.e., > 80% of the predicted value) in the Non-IMV Group. Female sex, and the need and duration of invasive mechanical were independently and negatively associated with the short physical performance battery score and handgrip strength. Patients who recovered from critical COVID-19 and who received invasive mechanical ventilation presented greater disability than those who were not invasively ventilated. However, they both showed marginal functional improvement during early recovery, regardless of the need for invasive mechanical ventilation. This might highlight the severity of disability caused by SARS-CoV-2.

Comparison of the clinical features and outcomes of severe seasonal influenza and COVID-19 patients in Tunisia between 2021 and 2022.

We compared patients diagnosed at a SARI (severe acute respiratory infections) surveillance site with COVID-19 and those with seasonal influenza to investigate the clinical differences, common features, and outcomes. We conducted a descriptive, retrospective study in the Medical Intensive Care Unit (ICU) at Abderrahman Mami Hospital between September 2021 and April 2022. Demographic, clinical, and biological data as well as outcomes were recorded for all patients. Among 223 SARI patients, 83 were confirmed COVID-19, and 22 were influenza positive. The distribution according to gender was similar; but patients with influenza were younger than those suffering from COVID-19(mean age 60.36 SD 17.28 vs. 61.88 SD 17.91; P = 0.601). In terms of underlying chronic diseases, the frequency was 84.3% in the COVID-19 group and 72.7% in the influenza group. COVID-19 patients had a longer duration of hospitalization (mean [SD], 9.51 days [8.47 days] vs. 7.33 days [8.82 days]; P = 0.003), and a more frequent need for invasive ventilation (80 [97.4%] vs. 20 [92.3]). Case fatality was also higher among this group compared to the latter (39 [47%] vs. 6 [27.3%], P = 0.01). This exploratory study suggests higher severity of COVID-19 compared to seasonal influenza among SARI hospitalized patients even during the Omicron wave. Further research on higher sample sizes is required to confirm this conclusion.

Response of Tocilizumab in Treating Severe to Critical COVID-19; Single-Centre Experience at a Tertiary Care Centre

Objective: To study the effectiveness of Tocilizumab in reducing mortality in severely or critically ill patients. Study Design: Quasi-experimental study Place and Duration of Study: Mayo Hospital, Lahore Pakistan, from Dec 2020 to May 2021. Methodology: The participants meeting the inclusion criteria of the study were allocated to an Experimental and a Control Arm based on age and oxygen requirements. The Experimental-Group was given Tocilizumab plus standard care, while the Control- Group received standard care only. Primary outcome was death, while secondary outcomes were the need for invasive ventilation and length of hospital stay. Results were analyzed after 28 days. Results: Among 81 patients, 60(74.1%) were males, 21(25.9%) were females. Of these, 44(54.3) received Tocilizumab plus Standard Care, while 37(45.7%) received Standard Care only. Out of 44 patients from the Tocilizumab-Group, 21(47.7%) survived, whereas, from 37 in the Standard Care-Group, 15(40.54%) survived at the end of 28 days. However, the difference in survival distributions between the two groups was not statistically significant (p=0.41). Conclusion: Tocilizumab was found to have no significant impact on improving the chances of survival and reducing the risk of Invasive Ventilation in COVID-19 patients. A wider confidence interval, however, cannot rule out the possibility of some benefit or harm. Hence, further studies are needed on this subject.

Comparison of lung ultrasound scoring systems for the prognosis of COVID‐19 in the emergency department: An international prospective cohort study

AbstractPurposeThe purpose of this study was to evaluate whether the lung ultrasound (LUS) scores applied to an international cohort of patients presenting to the emergency department (ED) with suspected COVID‐19, and subsequently admitted with proven disease, could prognosticate clinical outcomes.MethodsThis was an international, multicentre, prospective, observational cohort study of patients who received LUS and were followed for the composite primary outcome of intubation, intensive care unit (ICU) admission or death. LUS scores were later applied including two 12‐zone protocols (‘de Alencar score’ and ‘CLUE score’), a 12‐zone protocol with lung and pleural findings (‘Ji score’) and an 11‐zone protocol (‘Tung‐Chen score’). The primary analysis comprised logistic regression modelling of the composite primary outcome, with the LUS scores analysed individually as predictor variables.ResultsBetween April 2020 to April 2022, 129 patients with COVID‐19 had LUS performed according to the protocol and 24 (18.6%) met the composite primary endpoint. No association was seen between the LUS score and the composite primary end point for the de Alencar score [odds ratio (OR) = 1.04; 95% confidence interval (CI): 0.97–1.11; P = 0.29], the CLUE score (OR = 1.03; 95% CI: 0.96–1.10; P = 0.40), the Ji score (OR = 1.02; 95% CI: 0.97–1.07; P = 0.40) or the Tung‐Chen score (OR = 1.02; 95% CI: 0.97–1.08).DiscussionCompared to these earlier studies performed at the start of the pandemic, the negative outcome of our study could reflect the changing scenario of the COVID‐19 pandemic, including patient, disease, and system factors. The analysis suggests that the study may have been underpowered to detect a weaker association between a LUS score and the primary outcome.ConclusionIn an international cohort of adult patients presenting to the ED with suspected COVID‐19 disease who had LUS performed and were subsequently admitted to hospital, LUS severity scores did not prognosticate the need for invasive ventilation, ICU admission or death.

Effect of restrictive cumulative fluid balance on 28-day survival in invasively ventilated patients with moderate to severe ARDS due to COVID-19

This study aimed to evaluate the effect of two restrictive cumulative fluid balance (CFB) trends on survival and on major clinical outcomes in invasively ventilated patients with moderate to severe respiratory distress syndrome (ARDS) due to SARS-CoV-2. Prospective data collection was conducted on patients in the intensive care unit (ICU) originating from a tertiary university hospital. The primary outcomes were the risk association between the CFB trend during D0 to D7 and 28-day survival. The secondary outcomes were ICU mortality, in-hospital mortality, the need for invasive ventilation at D28, administration of vasoactive drugs at D7, time on invasive ventilation after D7, and length of ICU and hospital stay. 171 patients were enrolled in the study and divided according to their CFB trends during seven days of follow-up using model-based clustering [median CFB negative trend (n = 89) – 279 ml (− 664 to 203) and (n = 82) median CFB positive trend 1362 ml (619–2026)]. The group with CFB negative trend showed a higher chance of surviving 28-day in the ICU (HR: 0.62, 95% CI 0.41–0.94, p = 0.038). Moreover, this group had a reduced length of stay in the ICU, 11 (8–19) days versus 16.5 (9–29) days p = 0.004 and presented lower rates (OR = 0.22; 95% CI 0.09–0.52) of invasive ventilation after 28-days in the ICU. In patients invasively ventilated with moderate to severe ARDS due to COVID-19, the collective who showed a negative trend in the CFB after seven days of invasive ventilation had a higher chance of surviving 28 days in the ICU and lower length of stay in the ICU.

Study of Biochemical Parameters as Predictors for Need of Invasive Ventilation in Severely Ill COVID-19 Patients.

Though laboratory tests have been shown to predict mortality in COVID-19, there is still a dearth of information regarding the role of biochemical parameters in predicting the type of ventilatory support that these patients may require. The purpose of our retrospective observational study was to investigate the relationship between biochemical parameters and the type of ventilatory support needed for the intensive care of severely ill COVID-19 patients. We comprehensively recorded history, physical examination, vital signs from point-of-care testing (POCT) devices, clinical diagnosis, details of the ventilatory support required in intensive care and the results of the biochemical analysis at the time of admission. Appropriate statistical methods were used and P-values < 0.05 were considered significant. Receiver operating characteristics (ROC) analysis was performed and Area Under the Curve (AUC) of 0.6 to 0.7, 0.7 to 0.8, 0.8 to 0.9, and >0.9, respectively, were regarded as acceptable, fair, good, and exceptional for discrimination. Statistically significant differences (p<0.05) in Urea (p = 0.0351), Sodium (p = 0.0142), Indirect Bilirubin (p = 0.0251), Albumin (p = 0.0272), Aspartate Transaminase (AST) (p = 0.0060) and Procalcitonin (PCT) (p = 0.0420) were observed between the patients who were maintained on non-invasive ventilations as compared to those who required invasive ventilation. In patients who required invasive ventilation, the levels of Urea, Sodium, Indirect bilirubin, AST and PCT were higher while Albumin was lower. On ROC analysis, higher levels of Albumin was found to be acceptable indicator of maintenance on non-invasive ventilation while higher levels of Sodium and PCT were found to be fair predictor of requirement of invasive ventilation. Our study emphasizes the role of biochemical parameters in predicting the type of ventilatory support that is needed in order to properly manage severely ill COVID-19 patients.

The severity of hyponatremia worsens the outcome in pediatric intensive care patients

Objectives: Hyponatremia is known to increase mortality and morbidity in adult patients. However, the significance of hyponatremia in critically ill pediatric patients is unknown, unlike in adults. We tried to determine the prevalance of hyponatremia in critically ill children and whether the severity of hyponatremia contributes to hospital stay and mortality. Methods: The results of 190 patients who met the inclusion criteria and were admitted to the pediatric intensive care unit between April 2014 and April 2017 were analyzed. Results: Eighty-six (45.3%) patients developed hyponatremia at the time of hospitalization, and Hospital‑Acquired Hyponatremia (HAH) developed in 46 (24.2%) patients during the hospitalization. Fifty-eight (30.5%) patients were normonatremic. The patients in the HAH group were significantly more septic (p = 0.015). The duration of intensive care hospitalization was significantly longer in the HAH group (p &amp;lt; 0.001) and significantly less in the normonatremic group (p = 0.008). Total mortality was 41% (n = 78). There was no difference between the groups regarding mortality (p = 0.4). However, the degree of hyponatremia was associated with mortality. Mortality was 24.1% in mildly hyponatremic patients, 45.6% in moderate patients, and 58.8% in severe patients (OR: 2.636, 95% CI: 1.189-5.842; OR: 4.490, 95% CI:1.439-14.008, p = 0.01). We discovered that as hyponatremia severity increased, so did the length of stay in the intensive care unit, the need for invasive ventilation, and the need for vasoactive drugs (p = 0.009, p = 0.018, and p = 0.006, respectively). Conclusions: Unlike adults, the prognostic value of hyponatremia in terms of mortality has not been determined in critically ill children. However, as the severity of hyponatremia increased, it was seen that the length of stay in the intensive care unit and mortality increased.

Randomized controlled study to evaluate the safety and clinical impact of percutaneous auricular vagus nerve stimulation in patients with severe COVID-19.

Introduction: A severe course of COVID-19 is characterized by a hyperinflammatory state resulting in acute respiratory distress syndrome or even multi-organ failure along a derailed sympatho-vagal balance. Methods: In this prospective, randomized study, we evaluate the hypothesis that percutaneous minimally invasive auricular vagus nerve stimulation (aVNS) is a safe procedure and might reduce the rate of clinical complications in patients with severe course of COVID-19. In our study, patients with SARS-CoV-2 infection admitted to the intensive care unit with moderate-to-severe acute respiratory distress syndrome, however without invasive ventilation yet, were included and following randomization assigned to a group receiving aVNS four times per 24h for 3h and a group receiving standard of care (SOC). Results: A total of 12 patients were included (six in the aVNS and six in the SOC group). No side effects in aVNS were reported, especially no significant pain at device placement or during stimulation at the stimulation site or significant headache or bleeding after or during device placement or lasting skin irritation. There was no significant difference in the aVNS and SOC groups between the length of stay in the intensive care unit and at the hospital, bradycardia, delirium, or 90-day mortality. In the SOC group, five of six patients required invasive mechanical ventilation during their stay at hospital and 60% of them venovenous extracorporeal membrane oxygenation, compared to three of six patients and 0% in the aVNS group (p = 0.545 and p = 0.061). Discussion: Vagus nerve stimulation in patients with severe COVID-19 is a safe and feasible method. Our data showed a trend to a reduction of progression to the need of invasive ventilation and venovenous extracorporeal membrane oxygenation which encourages further research with larger patient samples.

A Study of Hypomagnesemia in Patients Admitted to the ICU.

Introduction After potassium, magnesium (Mg2+) is the most prevalent cation found intracellularly in the human body. The maintenance of excitability by Mg2+ and other cations is crucial for the neuromuscular junction to operate normally. Magnesium shortages are frequently overlooked compared to other electrolyte disorders such as hyponatremia, hypokalemia, and hypocalcemia. The present study aimed to study the factors and effects of hypomagnesemia amongintensive care unit (ICU) patients who are critically ill at atertiary care hospital. Methods This is a prospective observational study done among the patients who got admittedto the Medical ICUat Maharajahs Institute of Medical Sciences (MIMS), Nellimarla, Vizianagaram, from January 2020 to June 2021. A total of 100 patients were included in the study, of which 50 were cases and 50 were controls. The cases are those patients admitted to the medical ICU with critical illness and hypomagnesemia, and the controls are selected from those patients admitted with critical illness to the medical ICU with normal magnesium levels. Patients with severe infections, including sepsis, respiratory failure, cardiac failure,renal failure, cerebrovascular accidents (CVA), poisonings, and diabetic ketoacidosis (DKA), were included in the study. Patients who were treated with magnesium before admission to our ICU were excluded from this study. Serum magnesium was tested within24 hours of admission and is correlated with the outcomes of the patients in terms of APACHE II score, length of ICU stay, and requirementand duration ofventilatory support. Results Out of a total of 50 cases, 29 (58%) are of males. The mean age of cases was57.6 ∓ 8.2 years. Most cases were admitted due to organ failure (30%), followed by sepsis (26%) and poisoning (22%). The mean magnesium levels were 1.19 mg/dL among the cases, which was significantly lower when compared to the control group (2.16 mg/dL) (p-value= 0.01). The mean length of stay in the ICU was 6.12∓5.16 days in cases, whereas it was 5.28∓3.37 days in the control group (p-value = 0.33). 12% of cases needed non-invasive ventilation (NIV) when compared to 8% of controls (p-value= 0.50). 48% of the cases needed invasive ventilator support when compared to 28% in the control group (p-value= 0.03). The duration of invasive ventilation was higher among the cases (mean = 10 ∓3-17 days) compared to the controls(mean = 3 ∓2-4 days);p-value = 0.001.Mortality was higher in the case groupat 28% (14) and was 10% (5) in the control group (p-value = 0.02). Conclusion The need for invasive ventilation and duration of invasive ventilation were significantly higher among thepatients with hypomagnesemia compared to the patients with normal magnesium levels (p-value<0.05).Mortality was higher in the cases than in the controls (p-value<0.05).

Risk Factors and Outcomes Associated With Re-Intubation Secondary to Respiratory Failure in Patients With COVID-19 ARDS.

COVID-19 is associated with variable symptoms and clinical sequelae. Studies have examined the clinical course of these patients, finding a prolonged need for invasive ventilation and variable re-intubation rates. However, no research has investigated factors and outcomes related to re-intubation secondary to respiratory failure among patients with COVID-19 with ARDS. We conducted a single-center, retrospective study on subjects intubated for ARDS secondary to COVID-19. The primary outcome was re-intubation status; secondary outcomes were hospital and ICU stay and mortality. Data were analyzed using between-group comparisons using chi-square testing for categorical information and Student t test for quantitative data. Univariate and multivariate logistic regression was performed to determine factors related to re-intubation and mortality as dependent variables. One hundred and fourteen subjects were included, of which 32% required re-intubation. No between-group differences were detected for most demographic variables or comorbidities. No differences were detected in COVID-19 treatments, noninvasive respiratory support, mechanical circulatory support, or duration of ventilation. Midazolam (odds ratio [OR] 5.55 [95% CI 1.83-16.80], P = .002), fentanyl (OR 3.64 [95% CI 1.26-10.52], P = .02), and APACHE II scores (OR 1.08 [95% CI 1.030-1.147], P = .005) were independently associated with re-intubation (area under the curve = 0.81). Re-intubated subjects had extended hospital (36.7 ± 22.7 d vs 26.1 ± 12.1 d, P = .01) and ICU (29.6 ± 22.4 d vs 15.8 ± 10.4 d, P < .001) stays. More subjects died who failed extubation (49% vs 3%, P < .001). Age (OR 1.07 [95% CI 1.02-1.23], P = .005), male sex (OR 4.9 [95% CI 1.08-22.35], P = .041), positive Confusion Assessment Method for the ICU (CAM-ICU) (OR 5.43 [95% CI 1.58-18.62], P = .007), and re-intubation (OR 12.75 [95% CI 2.80-57.10], P < .001) were independently associated with death (area under the curve = 0.93). Midazolam, fentanyl, and higher APACHE II scores were independently associated with re-intubation secondary to respiratory failure in subjects with COVID-19-related ARDS. Furthermore, age, male sex, positive CAM-ICU, and re-intubation were independently associated with mortality. Re-intubation also correlated with prolonged hospital and ICU stay.

Less Invasive Surfactant Administration in Preterm Neonates: A Single Centre Experience at a Tertiary Care Teaching Hospital

Background Less Invasive Surfactant Administration (LISA) minimizes the need for invasive ventilation. As a result, it might improve survival rates in preterm newborns with respiratory distress syndrome (RDS), reducing long-term complications. This study explored the efficacy and potential benefits of the LISA in preterm newborns and its effect on short-term morbidity and mortality. Methods In this prospective observational study, 104 eligible preterm newborns &lt;35 weeks of gestational age were admitted to NICU from August 2020 to July 2021at a tertiary care teaching institute in central India with RDS were given surfactant using 5F feeding tube without intubation while spontaneously breathing on NCPAP. Regarding respiratory parameters, invasive ventilation in the first 72 hours of age, mean duration of both invasive ventilation and NCPAP, mean duration of oxygen requirement, complications, and neonatal outcomes were assessed. Results The mean duration of the NCPAP requirement and the mean total duration of the oxygen requirement were 41.77 hours and 81.3 hours, respectively. Twenty-seven neonates (25.96%) required invasive ventilation within 72 hours of age. Fourteen neonates (13.46%) required second dose of surfactant. Total mortality till NICU stay was 30.76% (n = 32). Incidences of surfactant reflux to the esophagus, desaturation during the intervention procedure, and procedure complications (pulmonary hemorrhage, pneumothorax) were also less during the LISA method. Conclusion LISA is an alternative, safe, and feasible method for surfactant delivery in spontaneously breathing preterm neonates on NCPAP. Therefore, adopting this procedure in a developing country to reduce short-term complications is possible. However, since a small number of neonates were included in this study, further extensive studies involving large numbers of preterm neonates and multiple centers are needed to generalize the results to the study population.

Decreased circulating CD73 and adenosine deaminase are associated with disease severity in hospitalized patients with COVID-19.

SARS-CoV-2 infection has been shown to result in increased circulating levels of adenosine triphosphate and adenosine diphosphate and decreased levels of adenosine, which has important anti-inflammatory activity. The goal of this pilot project was to assess the levels of soluble CD73 and soluble Adenosine Deaminase (ADA) in hospitalized patients with COVID-19 and determine if levels of these molecules are associated with disease severity. Plasma from 28 PCR-confirmed hospitalized COVID-19 patients who had varied disease severity based on WHO classification (6 mild/moderate, 10 severe, 12 critical) had concentrations of both soluble CD73 and ADA determined by ELISA. These concentrations were compared to healthy control plasma that is commercially available and was biobanked prior to the start of the pandemic. Additionally, outcomes such as WHO ordinal scale for disease severity, ICU admission, needed for invasive ventilation, hospital length of stay, and development of thrombosis during admission were used as markers of disease severity. Our results show that both CD73 and ADA are decreased during SARS-CoV-2 infection. The level of circulating CD73 is directly correlated to the severity of the disease defined by the need for ICU admission, invasive ventilation, and hospital length of stay. Low level of CD73 is also associated with clinical thrombosis, a severe complication of SARS-CoV-2 infection. Our study indicates that adenosine metabolism is down-regulated in patients with COVID-19 and associated with severe infection. Further large-scale studies are warranted to investigate the role of the adenosinergic anti-inflammatory CD73/ADA axis in protection against COVID-19.

Clinical characteristics of plastic bronchitis and risk factors for recurrence in children

To study the clinical characteristics of plastic bronchitis (PB) in children and investigate the the risk factors for recurrence of PB. This was a retrospective analysis of medical data of children with PB who were hospitalized in Children's Hospital of Chongqing Medical University from January 2012 to July 2022. The children were divided into a single occurrence of PB group and a recurrent PB group and the risk factors for recurrence of PB were analyzed. A total of 107 children with PB were included, including 61 males (57.0%) and 46 females (43.0%), with a median age of 5.0 years, and 78 cases (72.9%) were over 3 years old. All the children had cough, 96 children (89.7%) had fever, with high fever in 90 children. Seventy-three children (68.2%) had shortness of breath, and 64 children (59.8%) had respiratory failure. Sixty-six children (61.7%) had atelectasis and 52 children (48.6%) had pleural effusion. Forty-seven children (43.9%) had Mycoplasma pneumoniae infection, 28 children (26.2%) had adenovirus infection, and 17 children (15.9%) had influenza virus infection. Seventy-one children (66.4%) had a single occurrence of PB, and 36 cases (33.6%) had recurrent occurrence of PB (≥2 times). Multivariate logistic regression analysis showed that involvement of ≥2 lung lobes (OR=3.376) under bronchoscopy, continued need for invasive ventilation after initial removal of plastic casts (OR=3.275), and concomitant multi-organ dysfunction outside the lungs (OR=2.906) were independent risk factors for recurrent occurrence of PB (P<0.05). Children with pneumonia accompanied by persistent high fever, shortness of breath, respiratory failure, atelectasis or pleural effusion should be highly suspected with PB. Involvement of ≥2 lung lobes under bronchoscopy, continued need for invasive ventilation after initial removal of plastic casts, and concomitant multi-organ dysfunction outside the lungs may be risk factors for recurrent occurrence of PB.

Biomarker-Concordant Steroid Administration in Severe Coronavirus Disease-2019.

Although corticosteroids have become the standard of care for patients with coronavirus disease-2019 (COVID-19) on supplemental oxygen, there is growing evidence of differential treatment response. This study aimed to evaluate if there was an association between biomarker-concordant corticosteroid treatment and COVID-19 outcomes. This registry-based cohort study included adult COVID-19 hospitalized patients between January 2020 and December 2021 from 109 institutions. Patients with available C-reactive protein (CRP) levels within 48 h of admission were evaluated. Those on steroids before admission, stayed in the hospital for <48 h, or were not on oxygen support were excluded. Corticosteroid treatment was biomarker-concordant if given with high baseline CRP ≥150 mg/L or withheld with low CRP (<150 mg/L) and vice-versa was considered discordant (low CRP with steroids, high CRP without steroids). Hospital mortality was the primary outcome. Sensitivity analyses were conducted using varying CRP level thresholds. The model interaction was tested to determine steroid effectiveness with increasing CRP levels. Corticosteroid treatment was biomarker-concordant in 1778 (49%) patients and discordant in 1835 (51%). The concordant group consisted of higher-risk patients than the discordant group. After adjusting for covariates, the odds of in-hospital mortality were significantly lower in the concordant group than the discordant (odds ratio [95% confidence interval (C.I.)] = 0.71 [0.51, 0.98]). Similarly, adjusted mortality difference was significant at the CRP thresholds of 100 and 200 mg/L (odds ratio [95% C.I.] = 0.70 [0.52, 0.95] and 0.57 [0.38, 0.85], respectively), and concordant steroid use was associated with lower need for invasive ventilation for 200 mg/L threshold (odds ratio [95% C.I.] = 0.52 [0.30, 0.91]). In contrast, no outcome benefit was observed at CRP threshold of 50. When the model interaction was tested, steroids were more effective at reducing mortality as CRP levels increased. Biomarker-concordant corticosteroid treatment was associated with lower odds of in-hospital mortality in severe COVID-19.