Severity Of Respiratory Dysfunction Research Articles

Fluid Overload in Pediatric Acute Respiratory Distress Syndrome after Allogeneic Hematopoietic Cell Transplantation

AbstractThe aim of the study is to examine the relationship between fluid overload (FO) and severity of respiratory dysfunction in children post-hematopoietic cell transplantation (HCT) with pediatric acute respiratory distress syndrome (PARDS). This investigation was a secondary analysis of a multicenter retrospective cohort of children (1month to 21 years) post-allogeneic HCT with PARDS receiving invasive mechanical ventilation (IMV) from 2009 to 2014. Daily FO % (FO%) and daily oxygenation index (OI) were calculated for each patient up to the first week of IMV (day 0 = intubation). Linear mixed-effect regression was employed to examine whether FO% and OI were associated on any day during the study period. In total, 158 patients were included. Severe PARDS represented 63% of the cohort and had higher mortality (78 vs. 42%, p <0.001), fewer ventilator free days at 28 (0 [IQR 0–0] vs. 14 [IQR 0–23], p <0.001), and 60 days (0 [IQR 0–27] v. 45 [IQR 0–55], p <0.001) relative to non-severe PARDS. Increasing FO% was strongly associated with higher OI (p <0.001). For children with 10% FO, OI was higher by nearly 5 points (adjusted β 4.6, 95% CI [2.9, 6.3]). In subgroup analyses, the association between FO% and OI was strongest among severe PARDS (p <0.001) and during the first 3 days elapsed from intubation (p <0.001). FO% was associated with lower PaO2/FiO2 (adjusted β −1.92, 95% CI [−3.11, −0.73], p = 0.002), but not mean airway pressure (p = 0.746). In a multicenter cohort of children post-HCT with PARDS, FO was independently associated with oxygenation impairment. The associations were strongest among children with severe PARDS and early in the course of IMV.

ICU-Associated Costs during the Fourth Wave of the COVID-19 Pandemic in a Tertiary Hospital in a Low-Vaccinated Eastern European Country.

The COVID-19 pandemic has been associated with a tremendous financial and social impact. The pressure on healthcare systems worldwide has increased with each pandemic wave. The present study assesses the impact of the COVID-19 pandemic on healthcare-derived costs of critically ill patients during the fourth wave of the COVID-19 pandemic in a tertiary hospital in Romania. We prospectively included patients admitted to a single-centre intensive care unit (ICU) during the fourth wave of the COVID-19 pandemic. Median daily costs were calculated from financial records and divided in three groups: administrative costs, treatment costs and investigation costs. These were then compared to two retrospective cohorts of non-COVID-19 patients admitted to the same ICU during the same time interval in 2020 and 2019. Demographic data and the management of SARS-CoV-2 infection and of associated organ dysfunctions were recorded to identify risk factors for higher costs. Our results show that the COVID-19 pandemic has been associated with a 70.8% increase in total costs compared to previous years. This increase was mainly determined by an increase in medication and medical-device-related costs. We identified the following as risk factors for increased costs: higher degrees of lung involvement, severity of respiratory dysfunction, need for renal replacement therapy and the use of antiviral or immunomodulatory therapy. Costs were higher in patients who had a shorter duration of hospitalization. In conclusion, the COVID-19 pandemic is associated with increased costs for patients, and rapid measures need to be taken to ensure adequate financial support during future pandemic waves, especially in developing countries.

Hypercapnic ventilatory response in epilepsy patients treated with VNS: A case-control study.

Central CO2 chemoreception (CCR), a major chemical drive for breathing, can be quantified with a CO2 re-breathing test to measure the hypercapnic ventilatory response (HCVR). An attenuated HCVR correlates with the severity of respiratory dysfunction after generalized convulsive seizures and is a potential biomarker for sudden unexpected death in epilepsy (SUDEP) risk. Vagus nerve stimulation (VNS) may reduce SUDEP risk, but for unclear reasons the risk remains higher during the first 2 years after implantation. The vagus nerve has widespread connections in the brainstem, including key areas related to CCR. Here we examined whether chronic electrical stimulation of the vagus nerve induces changes in CCR. We compared the HCVR in epilepsy patients with or without an active VNS in a sex- and age-matched case-control study. Eligible subjects were selected from a cohort of patients who previously underwent HCVR testing. The HCVR slope, change in minute ventilation (VE) with respect to change in end tidal (ET) CO2 (∆ VE/ ∆ ETCO2) during the test was calculated for each subject. Key variables were compared between the two groups. Univariate and multivariate analyses were carried out for HCVR slope as dependent variable. A total of 86subjects were in the study. HCVR slope was significantly lower in the cases compared to the controls. Cases had longer duration of epilepsy and higher number of anti-epileptic drugs (AEDs) tried during lifetime. Having active VNS and ETCO2 were associated with a low HCVR slope while high BMI was associated with high HCVR slope in both univariate and multivariate analyses. We found having an active VNS was associated with relatively attenuated HCVR slope. Although duration of epilepsy and number of AEDs tried during lifetime was significantly different between the groups, they were not predictors of HCVR slope in subsequent analysis. Chronic electrical stimulation of the vagus nerve by VNS may be associated with an attenuated CCR [Correction added on 24 November 2021, after first online publication: The preceding sentence has been revised from “Chronic electrical stimulation of VNS nerve by VNS…”]. A larger prospective study may help to establish the time course of this effect in relation to the time of VNS implantation, whether there is a causal relationship, and determine how it affects SUDEP risk.

The ideal strategy of weaning from nasal continuous positive airway pressure in preterm infants: are we there yet?

Commentary on: Jensen CF, Sellmer A, Ebbesen F, et al. Sudden vs pressure wean from nasal continuous positive airway pressure in infants born before 32 weeks of gestation: a randomized clinical trial. JAMA Pediatr 2018 Jul 23. pii: 2687936. https://doi.org/10.1001/jamapediatrics.2018.2074. PMID: 30039171. The ideal strategy of weaning off nCPAP is not established. Premature discontinuation may lead to atelectasis, apnoea and bradycardia, respiratory distress, prolonged oxygen therapy and ultimately lung injury 1. On the other hand, undue prolonged therapy increases the risk of nasal trauma, gastric distension, pneumothorax and agitation 2. Previous studies showed conflicting results. Amatya et al. 3 found that more infants in the gradual wean group were successfully weaned off nCPAP as compared with the sudden wean group, with no difference in respiratory morbidity, weight gain, days on nCPAP and length of hospital stay. In contrast, Eze et al. 4 demonstrated that weaning CPAP in very preterm infants via sprinting (gradual increasing spontaneous breathing off nCPAP) versus weaning pressure down were comparable, regarding successful weaning and the occurrence of common neonatal morbidities. Jensen et al. have shown no difference in weight gain velocity from randomisation to 40 weeks PMA and in secondary outcomes between preterm infants born before 32 weeks of gestation, randomised to sudden weaning versus pressure weaning from nCPAP. The discrepancy in the findings of the Jensen et al.’ study and previous studies may be related to differences in gestational age and the severity of respiratory dysfunction, as infants enrolled in Jensen et al. and Amatya et al.’ studies had higher gestational age [median GA 30 (29–31), mean 28.7 ± 1.8 weeks, respectively], compared to Eze et al. [median 26.5 (23.6–30.6) weeks] and had less severe respiratory dysfunction as the need for surfactant was 36, 20%, respectively versus 63–73% in Eze et al. study. More infants <28 weeks of gestation at birth were successfully weaned from nCPAP during the first attempt in the pressure wean group compared with the sudden wean group. Similarly, Soe et al. 5 found that pressure weaning was more effective than cycling off nCPAP in infants born 24–27 weeks of gestation but not in infants over 28 weeks of gestation at birth. This may indicate that pressure weaning is more appropriate in these infants or that they should have different readiness to wean from nCPAP criteria such as lower FiO2 requirements, lower nCPAP pressure and older postnatal age. This is the largest RCT to date to compare sudden wean and pressure wean of very preterm infants from CPAP. However, the results of this study should be interpreted with caution, due to some limitations such as: Where do we go from here? In preterm infants <32 weeks of gestation, sudden discontinuation and gradual pressure weaning strategies seem to be equally effective approaches for weaning from nCPAP, and pressure wean may be preferred in infants who <28 weeks of gestation. However, future studies are warranted for refinement of readiness to wean from nCPAP criteria and to study the influence of different nCPAP weaning strategies on long-term pulmonary and neurodevelopmental outcomes. https://ebneo.org/2018/12/2018-12-weaning-from-nasal-cpap/ None. None.

Postictal immobility and generalized EEG suppression are associated with the severity of respiratory dysfunction.

The pathophysiology of sudden unexpected death in epilepsy (SUDEP) remains undetermined. Seizures are accompanied by respiratory dysfunction (RD). Postictal generalized electroencephalography (EEG) suppression (PGES) may follow generalized tonic-clonic seizures (GTCS). Following GTCS patients have impaired arousal and may be motionless. Patients with SUDEP are usually prone. Postictal immobility (PI) may contribute to SUDEP by not permitting repositioning of the head to allow unimpeded ventilation. To determine whether RD and/or ictal characteristics are associated with PI, we analyzed patients with GTCS in the epilepsy monitoring unit. We investigated for associations between PI duration and PGES, ictal/postictal oxygen saturation (SpO2 ), end-tidal CO2 (ETCO2 ), seizure localization, duration, and tonic and total convulsive phase duration. We investigated for linkage between PGES and these measures. Seventy patients with 181 GTCS and available SpO2 and/or ETCO2 data were studied. Simple linear regression analysis by seizures showed that PI duration was associated with peak periictal ETCO2 (p = 0.03), duration of oxygen desaturation (p = 0.005) and with SpO2 nadir (p = 0.02). PI duration was not associated with tonic, convulsive phase or total seizure duration. Analysis by patients also showed significant association of PI with RD. Duration of PI was longer following seizures with PGES (p < 0.001). PGES was not associated with the tonic, convulsive phase or total seizure duration. SpO2 nadir was lower in seizures with PGES (p = 0.046), ETCO2 peak change (p = 0.003) was higher, and duration of ETCO2 elevation (p = 0.03) was longer. Multivariable regression analysis showed that PGES and severe RD were associated with PI duration. The duration of PI and presence of PGES are associated with periictal RD. The duration of PI is also associated with the presence of PGES. Seizure duration or duration of the convulsive phase is not associated with PI or PGES. Interventions aimed at reversing impaired arousal and PI may reduce SUDEP risk.

G.P.260: Clinical diversity in patients with nemaline myopathy

Nemaline myopathy (NM) is a clinically heterogeneous congenital myopathy characterized by the presence of nemaline rods in the skeletal muscle fibers. We investigated the clinical variation and pathological features in Korean patients with NM. Thirteen patients were diagnosed through muscle biopsy. Six patients had the typical congenital type, which showed the motor development delay and hypotonia at birth. Six patients showed the mild childhood type with the gait disturbance. One patient had the intermediate congenital type, who needed mechanical ventilation. Regarding the distribution of weakness, five patients presented distal dominant weakness across the clinical type. High arched palates and feet deformity were observed. Equino varus deformity was identified in two patients. But, we could not find the cardiac muscle involvement. Typical nemaline rods were recognized on light microscopy with muscle biopsy from 11 patients. However, we could identify the nemaline filamentous aggregation in electro microscope (EM) from 2 patients. One of them showed a mitochondrial abnormality in EM. Type 1 fiber predominance was in all patients. The causative mutation form 8 patients was investigated, we found a missense heterozygous mutation in exon 1 of <i>TPM3</i> gene (c.32T>A, p.Met11Lys). Seven patients showed negative results in <i>ACTA1</i> gene. The thirteen patients in this study did not share much common feature except the dysmorphic appearance. The clinical diversity was prominent with the distribution of muscle weakness and the severity of respiratory dysfunction. This study showed the phenotypic heterogeneity of NM is not only with clinical features but also with pathological findings in our patient pool. Wider application of whole exome sequencing may help overcome the phenotypic and genotypic diversity in the diagnosis of NM.

Effects of a MAPK p38 inhibitor on lung function and airway inflammation in equine recurrent airway obstruction

It has been suggested that many of the beneficial effects of corticosteroids are mediated through mitogen-activated protein kinase (MAPK) p38 inhibition. To investigate the efficacy of the MAPK p38 inhibitor compound MRL-EQ1 to either prevent (Phase 1) or treat (Phase 2) recurrent airway obstruction (RAO) in horses. MRL-EQ1 was administered i.v. at a dosage of 0.75-1.5 mg/kg bwt q. 12 h. In Phase 1, susceptible horses in clinical remission were divided into 2 groups (n = 5/group), based on historical values of respiratory mechanics. All horses were entered in the study in pairs (one control, one treated horse) and exposed to the same environmental challenge (stabling, mouldy hay and dusty conditions). The treatment group received MRL-EQ1 for 14 days while the control horses were untreated during the same period. In Phase 2, affected horses were ranked by severity of respiratory dysfunction and split randomly into either dexamethasone or MRL-EQ1 treatment groups (n = 5/group). Bronchoalveolar lavage fluid, respiratory mechanic measurements, MRL-EQ1 plasma concentration and tumour necrosis factor (TNF) whole blood activity were evaluated sequentially. In Phase 1, MRL-EQ1 did not prevent the occurrence of clinical signs and pulmonary inflammation. However, treatment was associated with a reduction in severity and a delay in the onset of signs and a reduction in pulmonary neutrophilia. In Phase 2, plasma concentrations achieved resulted in ex vivo suppression of lipopolysaccharide-induced TNF production in equine blood. MRL-EQ1 did not improve airway inflammation or lung function and was associated in a dose dependent manner with behavioural (depression, excitability) and blood changes (neutrophilia, increased serum muscle enzyme concentrations). Inhibition of p38 in the horse was partially effective in reducing clinical signs and airway inflammation when administered prior to, but not during clinical exacerbation in RAO. Inhibitors of p38 MAPK with a better toxicity profile may be effective in the prevention or treatment of RAO.

Pulmonary Radiation Injury: Identification of Risk Factors Associated with Regional Hypersensitivity

Effective radiation treatment of thoracic tumors is often limited by radiosensitivity of surrounding tissues. Several experimental studies have suggested variations in radiosensitivity of different pulmonary regions. Mice and rat studies in part contradict each other and urge for a more detailed analysis. This study was designed to obtain a more comprehensive insight in radiation injury development, expression, and its regional heterogeneity in lung. The latter is obviously highly critical for optimization of radiotherapy treatment plans and may shed light on the mechanisms of lung dysfunction after irradiation. Six different but volume-equal regions in rat lung were irradiated. Whereas the severity of damage, as seen in histologic analysis, was comparable in all regions, the degree of lung dysfunction, measured as breathing rates, largely varied. During the pneumonitic phase (early: 6-12 weeks), the most sensitive regions contained a substantial part of alveolar lung parenchyma. Also, a trend for hypersensitivity was observed when the heart lay in the irradiation field. In the fibrotic phase (late: 34-38 weeks), lung parenchyma and heart-encompassing regions were the most sensitive. No impact of the heart was observed during the intermediate phase (16-28 weeks). The severity of respiratory dysfunction after partial thoracic irradiation is likely governed by an interaction between pulmonary and cardiac functional deficits. As a repercussion, more severe acute and delayed toxicity should be expected after combined lung and heart irradiation. This should be considered in the process of radiotherapy treatment planning of thoracic malignancies.

The Shrinking Lungs Syndrome in Systemic Lupus Erythematosus

The Shrinking Lungs Syndrome in Systemic Lupus Erythematosus

Reduction of Resuscitation Fluid Volumes in Severely Burned Patients Using Ascorbic Acid Administration

High-dose ascorbic acid (vitamin C) therapy (66 mg/kg per hour) attenuates postburn lipid peroxidation, resuscitation fluid volume requirements, and edema generation in severely burned patients. A prospective, randomized study at a university trauma and critical care center in Japan. Thirty-seven patients with burns over more than 30% of their total body surface area (TBSA) hospitalized within 2 hours after injury were randomly divided into ascorbic acid and control groups. Fluid resuscitation was performed using Ringer lactate solution to maintain stable hemodynamic measurements and adequate urine output (0.5-1.0 ml/kg per hour). In the ascorbic acid group (n = 19; mean burn size, 63% +/- 26% TBSA; mean burn index, 57 +/- 26; inhalation injury, 15/ 19), ascorbic acid was infused during the initial 24-hour study period. In the control group (n = 18; mean burn size, 53% +/- 17% TBSA; mean burn index, 47 +/- 13; inhalation injury, 12/18), no ascorbic acid was infused. We compared hemodynamic and respiratory measurements, lipid peroxidation, and fluid balance for 96 hours after injury. Two-way analysis of variance and Tukey test were used to analyze the data. Heart rate, mean arterial pressure, central venous pressure, arterial pH, base deficit, and urine outputs were equivalent in both groups. The 24-hour total fluid infusion volumes in the control and ascorbic acid groups were 5.5 +/- 3.1 and 3.0 +/- 1.7 mL/kg per percentage of burn area, respectively (P<.01). In the first 24 hours, the ascorbic acid group gained 9.2% +/- 8.2% of pretreatment weight; controls, 17.8% +/- 6.9%. Burned tissue water content was 6.1 +/- 1.8 vs 2.6 +/- 1.7 mL/g of dry weight in the control and ascorbic acid groups, respectively (P<.01). Fluid retention in the second 24 hours was also significantly reduced in the ascorbic acid group. In the control group, the ratio of PaO2 to fraction of inspired oxygen at 18, 24, 36, 48, and 72 hours after injury was less than that of the ascorbic acid group (P<.01). The length of mechanical ventilation in the control and ascorbic acid groups was 21.3 +/- 15.6 and 12.1 +/- 8.8 days, respectively (P<.05). Serum malondialdehyde levels were lower in the ascorbic acid group at 18, 24, and 36 hours after injury (P<.05). Adjuvant administration of high-dose ascorbic acid during the first 24 hours after thermal injury significantly reduces resuscitation fluid volume requirements, body weight gain, and wound edema. A reduction in the severity of respiratory dysfunction was also apparent in these patients.

Role of the thermic effect of food in malnutrition of patients with chronic obstructive pulmonary disease.

Malnutrition in patients with chronic obstructive pulmonary disease (COPD) is classically ascribed to an increased resting energy expenditure (REE) secondary to high cost of breathing. However, malnutrition correlates only weakly with the severity of respiratory dysfunction, which suggests other mechanisms. The aim of the present study was to determine the possible role of diet-induced thermogenesis (DIT). Therefore, we evaluated the relationship between DIT and nutritional status, in particular fat-free mass (FFM) estimated by bioelectrical impedance analysis in 26 patients with stable COPD (mean FEV1 +/- SEM = 36.5 +/- 3.8% of predicted). Ten patients were undernourished (weight < 90% of ideal body weight [IBW] and/or FFM < 69% of IBW), and 16 were normally nourished. Diet-induced thermogenesis was determined by comparing postprandial energy expenditure and REE, the latter being measured after an overnight fast and the former over 4 h after a mixed test meal of 0.4 times REE load. No statistical difference in DIT was found between undernourished and eutrophic patients. There was no relationship between DIT and nutritional or functional parameters, notably FFM. These results suggest that malnutrition is not a consequence of an increased DIT.

Surfactant abnormalities in patients with respiratory failure after multiple trauma.

We present a prospective study, designed to evaluate surfactant abnormalities in severely injured patients during the course of post-traumatic pulmonary dysfunction. Serially obtained bronchoalveolar lavage fluids from noncontused lung areas (in total, 132 samples from 17 patients) were analyzed for alveolar phospholipid composition and surfactant function in vitro during the first 14 days after trauma. The data were compared with those of 29 lavage samples obtained from 10 healthy control subjects and correlated to severity of respiratory failure. In the traumatized patients, the total lavage phospholipid content was unchanged, but there was a progressive decrease in the relative amounts of phosphatidylcholine (%PC) and phosphatidylglycerol and an increase in phosphatidylinositol, phosphatidylethanolamine, and sphingomyelin. These alterations were paralleled by a marked decrease in the hysteresis area of the surface tension isotherm. The decrease in %PC and reduction of hysteresis area were significantly correlated. The alterations in alveolar phospholipid composition and in vitro surfactant function were more pronounced in patients with severe respiratory failure. There was a significant inverse correlation between severity of respiratory dysfunction and %PC or hysteresis area for all traumatized patients. Protein leakage into the alveolar space was significantly higher in patients with severe respiratory failure and appeared to precede surfactant abnormalities in such patients. The neutrophil content in the alveolar space was markedly increased in all patients with multiple injuries however, no significant correlation with the noted alterations in alveolar phospholipid composition or surfactant function was found. We concluded that surfactant abnormalities occur during the course of post-traumatic pulmonary dysfunction and are correlated with the severity of respiratory failure.

Gated Radionuclide Ventriculography in the Evaluation of Cardiac Function in Duchenne's Muscular Dystrophy

Left ventricular ejection fractions were determined in 38 patients with Duchenne's muscular dystrophy. No significant correlation between the severity of respiratory dysfunction or age and cardiac function was seen. We suggest that the cardiac status of each patient should be evaluated separately from his respiratory status, particularly when long-term assisted ventilation is being considered.