Comparative effectiveness of alternative spontaneous breathing trial techniques: a systematic review and network meta-analysis of randomized trials.

BACKGROUND: The spontaneous breathing trial (SBT) technique that best balance successful extubation with the risk for reintubation is unknown. We sought to determine the comparative efficacy and safety of alternative SBT techniques. METHODS: We searched Medline, EMBASE, and the Cochrane Central Register of Controlled Trials from inception to February 2023 for randomized or quasi-randomized trials comparing SBT techniques in critically ill adults and children and reported initial SBT success, successful extubation, reintubation (primary outcomes) and mortality (ICU, hospital, most protracted; secondary outcome) rates. Two reviewers screened, reviewed full-texts, and abstracted data. We performed frequentist random-effects network meta-analysis. RESULTS: We included 40 RCTs (6716 patients). Pressure Support (PS) versus T-piece SBTs was the most common comparison. Initial successful SBT rates were increased with PS [risk ratio (RR) 1.08, 95% confidence interval (CI) (1.05-1.11)], PS/automatic tube compensation (ATC) [1.12 (1.01 -1.25), high flow nasal cannulae (HFNC) [1.07 (1.00-1.13) (all moderate certainty), and ATC [RR 1.11, (1.03-1.20); low certainty] SBTs compared to T-piece SBTs. Similarly, initial successful SBT rates were increased with PS, ATC, and PS/ATC SBTs compared to continuous positive airway pressure (CPAP) SBTs. Successful extubation rates were increased with PS [RR 1.06, (1.03-1.09); high certainty], ATC [RR 1.13, (1.05-1.21); moderate certainty], and HFNC [RR 1.06, (1.02-1.11); high certainty] SBTs, compared to T-piece SBTs. There was little to no difference in reintubation rates with PS (vs. T-piece) SBTs [RR 1.05, (0.91-1.21); low certainty], but increased reintubation rates with PS [RR 2.84, (1.61-5.03); moderate certainty] and ATC [RR 2.95 (1.57-5.56); moderate certainty] SBTs compared to HFNC SBTs. CONCLUSIONS: SBTs conducted with pressure augmentation (PS, ATC, PS/ATC) versus without (T-piece, CPAP) increased initial successful SBT and successful extubation rates. Although SBTs conducted with PS or ATC versus HFNC increased reintubation rates, this was not the case for PS versus T-piece SBTs.

Spontaneous Breathing Trial Techniques for Extubating Adults and Children Who Are Critically Ill: A Systematic Review and Meta-Analysis.

Importance: Considerable controversy exists regarding the best spontaneous breathing trial (SBT) technique to use. Objective: To summarize trials comparing alternative SBTs. Data Sources: Several databases (MEDLINE [from inception to February 2023], the Cochrane Central Register of Controlled Trials [in February 2023], and Embase [from inception to February 2023] and 5 conference proceedings (from January 1990 to April 2023) were searched in this systematic review and meta-analysis. Study Selection: Randomized trials directly comparing SBT techniques in critically ill adults or children and reporting at least 1 clinical outcome were selected. Data Extraction and Synthesis: Paired reviewers independently screened citations, abstracted data, and assessed quality for the systematic review and meta-analysis using Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA guidelines). Data were pooled using random-effects models. Main Outcomes and Measures: Primary outcomes included SBT success, extubation success, and reintubation. Results: The systematic review and meta-analysis identified 40 trials that included 6716 patients. Low-quality evidence (14 trials [n = 4459]) suggested that patients were not more likely to pass a pressure support (PS) compared with a T-piece SBT (risk ratio [RR], 1.04; 95% CI, 0.97-1.11; P = .31; I2 = 73%), unless 1 outlier trial accounting for all heterogeneity was excluded (RR, 1.09; 95% CI, 1.06-1.12; P < .001; I2 = 0% [13 trials; n = 3939]; moderate-quality evidence), but were significantly more likely to be successfully extubated (RR, 1.07; 95% CI, 1.04-1.10; P < .001; I2 = 0%; 16 trials [n = 4462]; moderate-quality evidence). Limited data (5 trials [n = 502]) revealed that patients who underwent automatic tube compensation/continuous positive airway pressure compared with PS SBTs had a significantly higher successful extubation rate (RR, 1.10; 95% CI, 1.00-1.21; P = .04; I2 = 0% [low-quality evidence]). Compared with T-piece SBTs, high-flow oxygen SBTs (3 trials [n = 386]) had significantly higher successful extubation (RR, 1.06; 95% CI, 1.00-1.11; P = .04; I2 = 0%) and lower reintubation (RR, 0.37; 95% CI, 0.21-0.65; P = <.001; I2 = 0% [both low-quality evidence]) rates. Credible subgroup effects were not found. Conclusions and Relevance: In this systematic review and meta-analysis, the findings suggest that patients undergoing PS compared with T-piece SBTs were more likely to be extubated successfully and more likely to pass an SBT, after exclusion of an outlier trial. Pressure support SBTs were not associated with increased risk of reintubation. Future trials should compare SBT techniques that maximize differences in inspiratory support.

Effects of prone positioning on ARDS outcomes of trauma and surgical patients: a systematic review and meta-analysis.

BACKGROUND: Prone position is an option for rescue therapy for acute respiratory distress syndrome. However, there are limited relevant data among trauma and surgical patients, who may be at increased risk for complications following position changes. This study aimed to identify the benefits and risks of proning in this patient subgroup. METHODS: Follow the PRISMA 2020, MEDLINE and EMBASE database searches were conducted. Additional search of relevant primary literature and review articles was also performed. A random effects model was used to estimate the PF ratio, mortality rate, mechanical ventilator days, and intensive care unit length of stay using Review Manager 5.4.1 software. RESULTS: Of 1,128 studies, 15 articles were included in this meta-analysis. The prone position significantly improved the PF ratio compared with the supine position (mean difference, 79.26; 95% CI, 53.38 to 105.13). The prone position group had a statistically significant mortality benefit (risk ratio [RR], 0.48; 95% CI, 0.35 to 0.67). Although there was no significant difference in the intensive care unit length of stay, the prone position significantly decreased mechanical ventilator days (-2.59; 95% CI, -4.21 to -0.97). On systematic review, minor complications were frequent, especially facial edema. There were no differences in local wound complications. CONCLUSIONS: The prone position has comparable complications to the supine position. With its benefits of increased oxygenation and decreased mortality, the prone position can be considered for trauma and surgical patients. A prospective multicenter study is warranted.

Effect of noninvasive respiratory support on interstitial lung disease with acute respiratory failure: A systematic review and meta-analysis.

Background: Primary studies have demonstrated the effectiveness of noninvasive respiratory supports, including noninvasive positive pressure ventilation (NIPPV) and high flow nasal cannula (HFNC), for improving oxygenation and ventilation in patients with interstitial lung diseases (ILDs) and acute respiratory failure (ARF). These studies have not been synthesized and are not included in current practice guidelines. This systematic review with meta-analysis synthesizes studies that compared the effectiveness of NIPPV, HFNC and conventional oxygen therapy (COT) for improving oxygenation and ventilation in ILD patients with ARF. Methods: MEDLINE, EMBASE and the Cochrane Library searches were conducted from inception to August 2023. An additional search of relevant primary literature and review articles was also performed. A random effects model was used to estimate the PF ratio (ratio of arterial oxygen partial pressure to fractional inspired oxygen), PaCO2 (partial pressure of carbon dioxide), mortality, intubation rate and hospital length of stay. Results: Ten studies were included in the systematic review and meta-analysis. Noninvasive respiratory supports demonstrated a significant improvement in PF ratio compared to conventional oxygen therapy (COT); the mean difference was 55.92 (95% CI [18.85-92.99]; p=0.003). Compared to HFNC, there was a significant increase in PF ratio in NIPPV (mean difference 0.45; 95% CI [0.12-0.79]; p=0.008). There were no mortality and intubation rate benefits when comparing NIPPV and HFNC; the mean difference was 1.1; 95% CI [0.83-1.44]; p=0.51 and 1.86; 95% CI [0.42-8.33]; p=0.42, respectively. In addition, there was a significant decrease in hospital length of stay in HFNC compared to NIPPV (mean difference 9.27; 95% Cl [1.45 - 17.1]; p=0.02). Conclusions: Noninvasive respiratory supports might be an alternative modality in ILDs with ARF. NIPPV demonstrated a potential to improve the PF ratio compared to HFNC. There was no evidence to support the benefit of NIPPV or HFNC in terms of mortality and intubation rate.

CYP3A4/P-glycoprotein inhibitors related colchicine toxicity mimicking septic shock.

Colchicine toxicity is uncommon when patients receive a therapeutic dose regularly. However, inadvertent drug interactions can result in unpredicted adverse outcomes. The toxicity of colchicine can manifest in various ways, ranging from mild and non-specific symptoms to severe form known as multiple organ dysfunction syndrome. This case highlights (1) the diagnostic challenge that arises when distinguishing between the severe manifestation of colchicine toxicity and septic shock and (2) concomitant prescription of colchicine with potent CYP3A4 and P-glycoprotein inhibitors (ie, clarithromycin) can lead to colchicine toxicity despite normal renal and hepatic clearance. Unfortunately, specific tests of colchicine toxicity were not routinely available. A high index of clinical suspicion and recognition of drug interactions with their common presentations are crucial for making diagnosis and management. Failure to recognise drug toxicity can result in poor outcomes.

Systemic lupus erythematosus associated with development of macrophage activation syndrome and disseminated aspergillosis.

PURPOSE: Macrophage activation syndrome (MAS) is a rare illness, especially in critically ill adults. The diagnosis of MAS is challenging, requiring the expertise of multiple specialists, and treatments for MAS can be associated with catastrophic complications. CLINICAL FEATURES: We describe the case of a 31-yr-old Vietnamese student who was diagnosed with cutaneous systemic lupus erythematosus (SLE) in November 2020 and was initiated on treatment with low-dose corticosteroids and hydroxychloroquine as an outpatient. Ten days later, she presented to hospital with decreased consciousness, fever, periorbital swelling, and hypotension necessitating intubation. Computed tomography angiography (CTA) and lumbar puncture did not show a stroke or central nervous system infection. Serology and clinical presentation were consistent with MAS. She was initially treated with 4.5 g pulse methylprednisolone and subsequently with the interleukin-1 receptor antagonist, anakinra, and maintenance corticosteroids because of persistently elevated inflammatory markers. Her intensive care unit stay was complicated by aspiration, airway obstruction due to fungal tracheobronchitis necessitating extracorporeal membrane oxygenation (ECMO), and ring-enhancing cerebral lesions, and, ultimately, massive hemoptysis resulting in death. CONCLUSIONS: Four features of this case merit discussion, including the: 1) infrequent association of SLE with MAS; 2) short interval between SLE diagnosis and critical illness; 3) manifestation of fungal tracheobronchitis with airway obstruction; and 4) lack of response to antifungal treatment while receiving ECMO.

RéSUMé: OBJECTIF: Le syndrome d'activation macrophagique (SAM) est une maladie rare, en particulier chez les adultes gravement malades. Le diagnostic d'un SAM est difficile à poser, nécessitant l'expertise de plusieurs spécialistes, et les traitements de ce syndrome peuvent être associés à des complications catastrophiques. CARACTéRISTIQUES CLINIQUES: Nous décrivons le cas d'une étudiante vietnamienne de 31 ans ayant reçu un diagnostic de lupus érythémateux disséminé (LED) cutané en novembre 2020; un traitement par corticostéroïdes à faible dose et hydroxychloroquine a été amorcé en ambulatoire. Dix jours plus tard, elle s'est présentée à l'hôpital avec une diminution de la conscience, de la fièvre, un gonflement périorbitaire et une hypotension nécessitant une intubation. L'angiographie par tomodensitométrie et la ponction lombaire n'ont pas révélé d'accident vasculaire cérébral ou d'infection du système nerveux central. La sérologie et la présentation clinique correspondaient à celles d'un SAM. Elle a d'abord été traitée avec 4,5 g de méthylprednisolone en injection ponctuelle, puis avec un antagoniste du récepteur à l'interleukine-1, l'anakinra et des corticostéroïdes d'entretien en raison de marqueurs inflammatoires élevés persistants. Son séjour en soins intensifs a été compliqué par une aspiration, une obstruction des voies aériennes due à une trachéobronchite fongique nécessitant une oxygénation par membrane extracorporelle (ECMO) et des lésions cérébrales avec rehaussement en anneau, et finalement une hémoptysie massive entraînant la mort. CONCLUSION: Quatre caractéristiques de ce cas méritent d'être discutées, soit: 1) l'association peu fréquente du lupus érythémateux disséminé avec un syndrome d'activation macrophagique; 2) le court intervalle entre le diagnostic de LED et la maladie grave; 3) l'apparition d'une trachéobronchite fongique avec obstruction des voies aériennes; et 4) l'absence de réponse au traitement antifongique pendant le traitement par ECMO.

A randomized, double-blind, placebo-controlled trial on the effect of intranasal corticosteroid as a treatment for moderate to severe obstructive sleep apnea with coexisting chronic rhinitis.

BACKGROUND: Chronic rhinitis is a common co-existing disease with obstructive sleep apnea (OSA). Current evidence on intranasal steroid efficacy as a treatment modality is scarce. OBJECTIVE: This study assessed the efficacy of intranasal steroid in moderate to severe OSA with coexisting chronic rhinitis. METHODS: A prospective randomized, double-blind, placebo-controlled trial was conducted in non-2nd to 3rd degree obese, non-severe oropharyngeal obstruction, moderate to severe OSA with coexisting chronic rhinitis (total nasal symptom score (TNSS) ≥ 6, BMI < 30 kg/m2, modified Mallampati < 3). We randomized the patients to receive intranasal steroid (fluticasone furoate, 110 mcg/day) or placebo for one-month duration. The primary end point was the change in apnea hypopnea index (AHI). RESULTS: A total of 34 patients were randomly assigned to receive intranasal steroid (N = 18) or placebo (N = 16). The adjusted absolute difference mean change of AHI did not show significant difference (11.5 ± 7.9 events/hour [95% CI; -4.9 to 27.8; p = 0.16]). Interestingly, significant reduction in non-supine respiratory disturbance index (RDI) (56.1 ± 21.9 events/hour [95% CI; 18.9 to 93.2; p = 0.01]) was observed in intranasal steroid group. When comparison was made within group, only intranasal steroid group demonstrated significant reduction in AHI, RDI, NREM RDI, TNSS, and Thai Pittsburgh sleep quality index (p = 0.02, 0.02, 0.01, 0.003, and < 0.001; respectively) after receiving the drug. CONCLUSIONS: In moderate to severe OSA patients with coexisting chronic rhinitis, intranasal steroid demonstrated significant reduction in obstructive respiratory events during non-supine sleep. Intranasal steroid may be considered as adjunctive or alternative to OSA treatment.

Critical care management of pulmonary arterial hypertension in pregnancy: the pre-, peri- and post-partum stages.

The mortality rate of pulmonary hypertension in pregnancy is 25%-56%. Pulmonary arterial hypertension is the highest incidence among this group, especially in young women. Despite clear recommendation of pregnancy avoidance, certain groups of patients are initially diagnosed during the gestational age step into the third trimester. While the presence of right ventricular failure in early gestation is usually trivial, it can be more severe in the late trimester. Current evidence shows no consensus in the management and serious precautions for each stage of the pre-, peri- and post-partum periods of this specific group. Pulmonary hypertension-targeted drugs, mode of delivery, type of anesthesia, and some avoidances should be planned among a multidisciplinary team to enhance maternal and fetal survival opportunities. Sudden circulatory collapse from cardiac decompensation during the peri- and post-partum phases is detrimental, and mechanical support such as extracorporeal membrane oxygenation should be considered for mitigating hemodynamics and extending cardiac recovery time. Our review aims to explain the pathophysiology of pulmonary arterial hypertension and summarize the current evidence for critical management and precautions in each stage of pregnancy.

Multimodality treatment in immunocompromised patients with severe COVID-19: the role of IL-6 inhibitor, intravenous immunoglobulin, and haemoperfusion.

Cytokine release syndrome (CRS) is known to be associated with severe coronavirus disease 2019 (COVID-19). Multiple anti-inflammatory therapies such as tocilizumab, corticosteroids, intravenous immunoglobulin (IVIG), and haemoadsorption or haemoperfusion have been used to combat this life-threatening condition. However, immunocompromised hosts are often omitted from research studies, and knowledge on the clinical efficacy of these therapies in immunocompromised patients is therefore limited. We report two cases of immunocompromised patients with severe COVID-19-related CRS requiring mechanical ventilation who were treated with multimodality treatment consisting of tocilizumab, IVIG, and haemoperfusion. Within 48 h, both patients showed clinical improvement with PaO2:FiO2 ratio and haemodynamic stability. Both survived to discharge. There were no adverse events following these therapies. In conclusion, combined therapeutic modalities, possibly tailored to individual inflammatory profiles, are promising treatment for severe COVID-19 infection in the immunocompromised host. Timely administration of adjunctive therapies that alleviate overwhelming inflammation may provide the best outcome.

Salbutamol-induced lactic acidosis in status asthmaticus survivor.

BACKGROUND: Salbutamol-induced lactic acidosis is a rare presentation that could manifest in specific clinical context as acute asthmatic attack treatment. An increase of glycolysis pathway leading to pyruvate escalation is the mechanism of hyperlactatemia in ß2-adrenergic agonist drug. CASE PRESENTATION: A 40-year-old man who had poor-controlled asthma, presented with progressive dyspnea with coryza symptom for 6 days. He was intubated and admitted into medical intensive care unit due to deteriorated respiratory symptom. Severe asthmatic attack was diagnosed and approximate 1.5 canisters of salbutamol inhaler was administrated within 24 h of admission. Initial severe acidosis consisted of acute respiratory acidosis from ventilation-perfusion mismatch and acute metabolic acidosis resulting from bronchospasm and hypoxia-related lactic acidosis, respectively. The lactate level was normalized in 6 h after hypoxemia and ventilation correction. Given the lactate level re-elevated into a peak of 4.6 mmol/L without signs of tissue hypoxia nor other possible etiologies, the salbutamol toxicity was suspected and the inhaler was discontinued that contributed to rapid lactate clearance. The patient was safely discharged on the 6th day of admission. CONCLUSION: The re-elevation of serum lactate in status asthmaticus patient who had been administrated with the vast amount of ß2-adrenergic agonist should be considered for salbutamol-induced lactic acidosis and promptly discontinued especially when there were no common potentials.

Decontamination and reuse of surgical masks and N95 filtering facepiece respirators during the COVID-19 pandemic: A systematic review.

OBJECTIVES: Surgical masks and N95 filtering facepiece respirators (FFRs) prevent the spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and protect medical personnel. Increased demands for surgical masks and N95 FFRs during the coronavirus disease 2019 (COVID-19) pandemic has resulted in the shortage crisis. However, there is no standard protocol for safe reuse of the N95 FFRs. In this systematic review, we aimed to evaluate the effectiveness of existing decontamination methods of surgical masks and N95 FFRs and provide evidence-based recommendations for selecting an appropriate decontamination method. METHODS: We performed systematic searches of Ovid MEDLINE and Ovid EMBASE electronic databases. The last search was performed April 11, 2020. Any trials studying surgical masks and/or N95 FFRs decontamination were included. Outcomes were disinfections of virus and bacteria, restoration of the filtration efficiency, and maintenance of the physical structure of the mask. RESULTS: Overall, 15 studies and 14 decontamination methods were identified. A low level of evidence supported 4 decontamination methods: ultraviolet (UV) germicidal irradiation (9 studies), moist heat (5 studies), microwave-generated steam (4 studies), and hydrogen peroxide vapor (4 studies). Therefore, we recommended these 4 methods, and we recommended against use were given for the other 10 methods. CONCLUSIONS: A low level of evidence supported the use of UV germicidal irradiation, moist heat, microwave-generated steam, and hydrogen peroxide vapor for decontamination and reuse of N95 FFRs. These decontamination methods were effective for viral and bacterial disinfection as well as restoration of the filtration efficiency, and the physical structure of the FFRs.

Endotoxemia and circulating bacteriome in severe COVID-19 patients.

BACKGROUND: When severe, COVID-19 shares many clinical features with bacterial sepsis. Yet, secondary bacterial infection is uncommon. However, as epithelium is injured and barrier function is lost, bacterial products entering the circulation might contribute to the pathophysiology of COVID-19. METHODS: We studied 19 adults, severely ill patients with COVID-19 infection, who were admitted to King Chulalongkorn Memorial Hospital, Bangkok, Thailand, between 13th March and 17th April 2020. Blood samples on days 1, 3, and 7 of enrollment were analyzed for endotoxin activity assay (EAA), (1 → 3)-ß-D-glucan (BG), and 16S rRNA gene sequencing to determine the circulating bacteriome. RESULTS: Of the 19 patients, 13 were in intensive care and 10 patients received mechanical ventilation. We found 8 patients with high EAA (≥ 0.6) and about half of the patients had high serum BG levels which tended to be higher in later in the illness. Although only 1 patient had a positive blood culture, 18 of 19 patients were positive for 16S rRNA gene amplification. Proteobacteria was the most abundant phylum. The diversity of bacterial genera was decreased overtime. CONCLUSIONS: Bacterial DNA and toxins were discovered in virtually all severely ill COVID-19 pneumonia patients. This raises a previously unrecognized concern for significant contribution of bacterial products in the pathogenesis of this disease.

Successful prone positioning after recent caesarean section in severe ARDS with postpartum pulmonary haemorrhage.

A 35-year-old Thai women (gravida 3, para 0) at 36 weeks and five days of gestation was admitted to a delivery room due to premature rupture of membrane. She was diagnosed with Escherichia coli with extended-spectrum beta-lactamase (ESBL) chorioamnionitis and septic shock leading to signs of fetal distress. She underwent emergency caesarean section. Post-operatively, the patient developed severe acute respiratory distress syndrome (ARDS), disseminated intravascular coagulation (DIC), massive pulmonary haemorrhage, and intra-abdominal bleeding. Lung protective strategy and recruitment manoeuvres were applied; however, her oxygenation and haemodynamic parameters worsened. Twenty consecutive hours of prone positioning was performed as a rescue procedure to improve patient's oxygenation and allow the patient to undertake surgical re-exploration for abdominal compartment syndrome management safely. Neither high ventilator setting nor re-positioning was needed after the second operation.

Successful multimodality management of severe pulmonary arterial hypertension during pregnancy with VA-ECMO and atrial septostomy using stent.

A 30-year-old Thai woman (gravida 1, para 0) at 33 weeks gestation was referred to our hospital due to acute right ventricular failure. Pulmonary vasodilators were gradually administered before delivery. On the verge of sudden postpartum cardiac circulation collapse, she was resuscitated with veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Abdominal compartment syndrome was developed in the early period of the mechanical support. Knowledge of pathophysiology about pulmonary arterial hypertension during pregnancy was applied. Atrial septostomy was the effective procedure for discontinuing mechanical support (VA-ECMO) corresponding to the suitable timing for maximal effect of pulmonary vasodilators. The patient and her child were safe and discharged in 2 months after the admission.