Objective: To investigate post-intubation laryngeal complications in severe COVID-19 patients. Methods: From September 2020 to April 2021, consecutive patients presenting with laryngological symptoms following severe COVID-19 infection and related intubation were included. Demographic, age, gender, comorbidities, symptoms, intubation duration, tracheostomy features, and laryngeal findings were collected. Videolaryngostroboscopy findings were analyzed by two senior laryngologists in a blind manner. Results: Forty-three patients completed the evaluations. The intubation duration was <14 days in 22 patients (group 1) and >14 days in 21 patients (group 2). The following abnormalities were found on an average post-intubation time of 51.6 days: posterior glottic stenosis (N=14), posterior commissure hypertrophy (N=19) or laryngeal diffuse edema (N=10), granuloma (N=8), laryngeal necrosis (N=2), vocal fold atrophy (N=2), subglottic stenosis (N=1) and glottic flange (N=1). Sixteen patients required surgical treatment (N=17 procedures). The number of intubation days was significantly higher in patients with posterior glottic stenosis (26.1 ± 9.4) compared with those presenting posterior commissure hypertrophy (11.5 ± 2.9) or granuloma (15.1 ± 5.8; p<0.001). Fourteen patients required surgical management. Conclusion: Prolonged intubation used in severe COVID-19 patients is associated with significant laryngeal disorders. Patients with a history of >2-week intubation have a higher risk of posterior glottic stenosis.
Patients with chronic obstructive pulmonary disease (COPD) are affected by episodes of respiratory exacerbations, some of which can be severe and may necessitate respiratory support. Prolonged invasive mechanical ventilation is associated with increased mortality rates. Persistent failure to discontinue invasive mechanical ventilation is a major issue in patients with COPD. Pure or mixed metabolic alkalosis is a common finding in the intensive care unit (ICU) and is associated with a worse outcome. In patients with COPD, the condition is called post-hypercapnic alkalosis and is a complication of mechanical ventilation. Reversal of metabolic alkalosis may facilitate weaning from mechanical ventilation of patients with COPD. Acetazolamide, a non-specific carbonic anhydrase inhibitor, is one of the drugs employed in the ICU to reverse metabolic alkalosis. The drug is relatively safe, undesirable effects being rare. The compartmentalization of the different isoforms of the carbonic anhydrase enzyme may, in part, explain the lack of evidence of the efficacy of acetazolamide as a respiratory stimulant. Recent findings suggest that the usually employed doses of acetazolamide in the ICU may be insufficient to significantly improve respiratory parameters in mechanically ventilated patients with COPD. Randomized controlled trials using adequate doses of acetazolamide are required to address this issue.
BACKGROUND Generalized convulsive status epilepticus (GCSE) is a frequent medical emergency. GCSE treatment focuses on the administration of benzodiazepines followed by a second-line antiepileptic drug (AED). Despite this stepwise strategy, GCSE is not controlled in one-quarter of patients and is associated with protracted hospitalization, high mortality, and long-term disability. Valproic acid (VPA) is an AED with good tolerability and neuroprotective properties. OBJECTIVE This study aims to demonstrate that administration of VPA as an adjuvant for first- and second-line treatment in GCSE can improve outcomes. METHODS A multicenter, double-blind, randomized controlled trial was conducted, comparing VPA with a placebo in adults admitted to intensive care units (ICUs) for GCSE in France. GCSE was diagnosed by specifically trained ICU physicians according to standard criteria. All patients received standard of care, including a benzodiazepine and a second-line AED (not VPA), at the discretion of the treating medical team. In the intervention arm, VPA was administered intravenously at a loading dose of 30 mg/kg over 15 minutes, followed by a continuous infusion of 1 mg/kg/hour over the next 12 hours. In the placebo group, an identical intravenous administration of 0.9% saline was used. The primary outcome was the proportion of patients discharged alive from the hospital by day 15. Secondary outcomes were frequency of refractory and super refractory GCSE, ICU-related morbidity, adverse events related to VPA, and cognitive dysfunction at 3 months. Statistical analyses will be performed according to the intent-to-treat principle. RESULTS The first patient was randomized on February 18, 2013, and the last patient was randomized on July 7, 2018. Of 248 planned patients, 98.7% (245/248) were enrolled across 20 ICUs. At present, data management is still ongoing, and all parties involved in the trial remain blinded. CONCLUSIONS The Valproic Acid as an Adjuvant Treatment for Generalized Convulsive Status Epilepticus (VALSE) trial will evaluate whether the use of VPA as an adjuvant for first- and second-line treatment in GCSE improves outcomes. CLINICALTRIAL ClinicalTrials.gov NCT01791868; https://clinicaltrials.gov/ct2/show/NCT01791868. INTERNATIONAL REGISTERED REPORT DERR1-10.2196/22511
Introduction : Agitation, confusion and poor mask tolerance are main factors contributing to poor adherence and often failure of acute NIV. However, there is limited data in the use of sedation to enhance NIV adherence. Methods : Patients requiring NIV were included in a 12 month period from January to December 2012. Patient and health care providers (HCP) perceptions surrounding the use of sedation and comfort were measured following cessation of NIV and repeated 6 weeks post discharge. Results : 42 patients, 57% female (age 68.9±12.9 years) were included. 30% experienced an episode of agitation, confusion or aggressive behaviour. 21% were prescribed but only 11% received sedation during NIV. A higher tolerance throughout, and some perceived benefit during initiation of NIV was observed in patients in the ‘sedated’ group (figure1). 21% died prior to the 6 week follow up. Of the survivors, only 16% completed the post-discharge questionnaire. Prior to discharge, 50% of patients reported that they would accept sedation if offered and 66% perceived that this would improve their adherence. Conclusion : Sedation may aid NIV tolerance and adherence. Furthermore, it is acceptable to patients. These data highlight the need to consider the use of supplemental sedation during the use of acute NIV.
The authors have no conflicts of interest. The peer review history for this article is available at https://www.webofscience.com/api/gateway/wos/peer-review/10.1111/coa.14078. Data are available on request.
Anxiety results from the anticipation of a threat and might be associated with poor outcome in the critically ill. This study aims at showing that anxiety at admission in critically ill patients is associated with new organ failure over the first 7 days of ICU hospitalization independently of baseline organ failure at admission.Prospective multicenter cohort study.Three mixed ICU from April 2014 to December 2017.Coma-, delirium-, and invasive mechanical ventilation-free patients admitted to the ICU were included.None."State anxiety" was assessed using the state component of the State-Trait Anxiety Inventory State. Severity of illness was measured using Simplified Acute Physiology Score II and Sequential Organ Failure Assessment scores. Primary endpoint was a composite of occurrence of death or new organ failure in the first 7 days after admission. Three hundred ninety-one patients were included; 159 of 391 women (40.7%); median age 63 years (49-74 yr); median Simplified Acute Physiology Score II 28 (19-37). Two hundred three out of 391 patients (51.9%) reported moderate to severe anxiety (State-Trait Anxiety Inventory State ≥ 40). One hundred two out of 391 patients (26.1%) developed a new organ failure. After adjustment to Simplified Acute Physiology Score II and Sequential Organ Failure Assessment, State-Trait Anxiety Inventory State greater than or equal to 40 was associated with the primary endpoint (odds ratio, 1.94; 95% CI, 1.18-3.18; p = 0.009) and respiratory failure. In post hoc analysis, State-Trait Anxiety Inventory State greater than or equal to 40 was associated with new organ failure independently and notably of respiratory status at admission (dyspnea-Visual Analogic Scale and PaCO2 ≥ 45 mm Hg).Moderate to severe anxiety at ICU admission is associated with early occurrence of new organ failure in critically ill patients, independently of respiratory status and severity of critical illness. The causality link could be addressed in an interventional trial.
Abstract Background We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7 , with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10 −4 ) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10 −4 ). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10 −3 ), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10 −8 ). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10 −5 ). Conclusions Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.
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