Gastric pressure monitoring unveils abnormal patient-ventilator interaction related to active expiration: a retrospective observational study.

BACKGROUND: Patient-ventilator dyssynchrony is frequently observed during assisted mechanical ventilation (MV). However, the effects of expiratory muscle contraction on patient-ventilator interaction are underexplored. We hypothesized that active expiration would affect patient-ventilator interaction and we tested our hypothesis in a mixed cohort of invasively ventilated patients with spontaneous breathing activity. METHODS: This is a retrospective observational study involving patients on assisted MV who had their esophageal (Pes) and gastric (Pgas) pressures monitored for clinical purposes. Active expiration was defined as Pgas rise (ΔPgas) ≥1.0 cmH2O during expiratory flow without a corresponding change in diaphragmatic pressure (Pdi). Waveforms of Pes, Pgas, Pdi, flow, and airway pressure (Paw) were analyzed to identify and characterize abnormal patient-ventilator interaction. RESULTS: We identified 76 patients with Pes and Pgas recordings, of whom 58 demonstrated active expiration with a median ΔPgas of 3.4 cmH2O (IQR=2.4-5.3) observed in this subgroup. Among these 58 patients, 23 presented the following events associated with expiratory muscle activity: (1) distortions in Paw and flow that resembled ineffective efforts, (2) distortions similar to autotriggering, (3) multiple triggering, (4) prolonged ventilatory cycles with biphasic inspiratory flow, with a median % (IQR) increase in mechanical inflation time and tidal volume of 54% (44-70%) and 25% (8-35%), respectively and (5) breathing exclusively by expiratory muscle relaxation. Gastric pressure monitoring was required to identify the association of active expiration with these events. Respiratory drive, assessed by the rate of inspiratory Pes decrease, was significantly higher in patients with active expiration (median [IQR] dPes/dt: 12.7 [9.0-18.5] vs 9.2 [6.8-14.2] cmH2O/sec; p<0.05). CONCLUSIONS: Active expiration can impair patient-ventilator interaction in critically ill patients. Without documenting Pgas, abnormal patient-ventilator interaction associated with expiratory muscle contraction may be mistakenly attributed to a mismatch between the patient´s inspiratory effort and mechanical inflation. This misinterpretation could potentially influence decisions regarding clinical management.

Airway pressure morphology and respiratory muscle activity during end-inspiratory occlusions in pressure support ventilation.

BACKGROUND: The driving pressure of the respiratory system is a valuable indicator of global lung stress during passive mechanical ventilation. Monitoring lung stress in assisted ventilation is indispensable, but achieving passive conditions in spontaneously breathing patients to measure driving pressure is challenging. The accuracy of the morphology of airway pressure (Paw) during end-inspiratory occlusion to assure passive conditions during pressure support ventilation has not been examined. METHODS: Retrospective analysis of end-inspiratory occlusions obtained from critically ill patients during pressure support ventilation. Flow, airway, esophageal, gastric, and transdiaphragmatic pressures were analyzed. The rise of gastric pressure during occlusion with a constant/decreasing transdiaphragmatic pressure was used to identify and quantify the expiratory muscle activity. The Paw during occlusion was classified in three patterns, based on the differences at three pre-defined points after occlusion (0.3, 1, and 2 s): a "passive-like" decrease followed by plateau, a pattern with "clear plateau," and an "irregular rise" pattern, which included all cases of late or continuous increase, with or without plateau. RESULTS: Data from 40 patients and 227 occlusions were analyzed. Expiratory muscle activity during occlusion was identified in 79% of occlusions, and at all levels of assist. After classifying occlusions according to Paw pattern, expiratory muscle activity was identified in 52%, 67%, and 100% of cases of Paw of passive-like, clear plateau, or irregular rise pattern, respectively. The driving pressure was evaluated in the 133 occlusions having a passive-like or clear plateau pattern in Paw. An increase in gastric pressure was present in 46%, 62%, and 64% of cases at 0.3, 1, and 2 s, respectively, and it was greater than 2 cmH2O, in 10%, 20%, and 15% of cases at 0.3, 1, and 2 s, respectively. CONCLUSIONS: The pattern of Paw during an end-inspiratory occlusion in pressure support cannot assure the absence of expiratory muscle activity and accurate measurement of driving pressure. Yet, because driving pressure can only be overestimated due to expiratory muscle contraction, in everyday practice, a low driving pressure indicates an absence of global lung over-stretch. A measurement of high driving pressure should prompt further diagnostic workup, such as a measurement of esophageal pressure.

Neural Network-Enabled Identification of Weak Inspiratory Efforts during Pressure Support Ventilation Using Ventilator Waveforms.

During pressure support ventilation (PSV), excessive assist results in weak inspiratory efforts and promotes diaphragm atrophy and delayed weaning. The aim of this study was to develop a classifier using a neural network to identify weak inspiratory efforts during PSV, based on the ventilator waveforms. Recordings of flow, airway, esophageal and gastric pressures from critically ill patients were used to create an annotated dataset, using data from 37 patients at 2-5 different levels of support, computing the inspiratory time and effort for every breath. The complete dataset was randomly split, and data from 22 patients (45,650 breaths) were used to develop the model. Using a One-Dimensional Convolutional Neural Network, a predictive model was developed to characterize the inspiratory effort of each breath as weak or not, using a threshold of 50 cmH2O*s/min. The following results were produced by implementing the model on data from 15 different patients (31,343 breaths). The model predicted weak inspiratory efforts with a sensitivity of 88%, specificity of 72%, positive predictive value of 40%, and negative predictive value of 96%. These results provide a 'proof-of-concept' for the ability of such a neural-network based predictive model to facilitate the implementation of personalized assisted ventilation.

COVID-19-associated pulmonary aspergillosis in patients with severe SARS-CoV-2 infection: A single-center observational study from Greece.

INTRODUCTION: COVID-19-associated pulmonary aspergillosis (CAPA) is a serious complication affecting patients with severe SARS-CoV-2 infection, and is associated with increased mortality. OBJECTIVE: The objective of this study was to investigate potential risk factors, and to estimate the incidence and mortality in patients diagnosed with CAPA. METHODS: A single-center retrospective observational study was conducted on patients admitted to the intensive care unit (ICU) with severe COVID-19 from October 2020 to May 2022. Patients with deterioration of their clinical status were evaluated with serum galactomannan (GM) for probable CAPA. Baseline demographic patient characteristics, vaccination status, and time period during which each patient was infected with SARS-CoV-2 were obtained, and risk stratification according to underlying comorbidities was performed in an effort to assess various risk factors for CAPA. The incidence of CAPA in the entire cohort was measured, and mortality rates in the CAPA and non-CAPA groups were calculated and compared. RESULTS: Of 488 patients admitted to the ICU, 95 (19.4%) had deterioration of their clinical status, which prompted testing with serum GM. Positive serum testing was observed in 39/95 patients, with an overall CAPA incidence in the entire study cohort reaching 7.9% (39/488). The mortality rate was 75% (42/56) in the non-CAPA group that was tested for serum GM, and 87.2% (34/39) in the CAPA group (P = 0.041). Multivariable Cox regression hazard models were tested for 28- and 90-day survival from ICU admission. An invasive pulmonary aspergillosis (IPA) risk-stratified cox regression model corrected for the SARS-CoV-2 variant of the patient identified the diagnosis of probable CAPA and elevated procalcitonin (PCT) levels measured at least 10 days after ICU admission, as significantly associated with death in the IPA-risk subgroup only, with hazard ratio (HR): 3.687 (95% confidence interval [CI], 1.030-13.199, P = 0.045) for the diagnosis of probable CAPA, and HR: 1.022 (95% CI, 1.003-1.042, P = 0.026) for every 1 ng/mL rise in PCT. CONCLUSIONS: Patients in the IPA-risk subgroup that were diagnosed with CAPA had a lower 90-day survival when compared to patients in the same group without a CAPA diagnosis.

Esophageal and transdiaphragmatic pressure swings as indices of inspiratory effort.

AIM: To describe the correlation between the inspiratory esophageal and transdiaphragmatic pressure swings (ΔPes and ΔPdi), easily measured indices of inspiratory effort, with the gold-standard, the transdiaphragmatic pressure time product (PTPPdi/min), and assess the accuracy of swing pressures in predicting very high or low effort. METHOD: Retrospective analysis of data from patients enrolled in four previous studies. ROC curves of ΔPes and ΔPdi values for specific PTPPdi/min thresholds (50, 150, 200 cmH2O × sec/min) were constructed, and the diagnostic accuracy of different thresholds of swing values were computed. RESULTS: A threshold of inspiratory ΔP<7cmH2O can be used to identify most patients with low effort, as lower ΔP thresholds have low sensitivity. Thresholds of inspiratory ΔP>14-18cmH2O can be used to identify patients with very high inspiratory effort (PTPPdi/min> 200 cmH2O × sec/min). CONCLUSIONS: The results of this study can help clinicians better select and interpret thresholds of ΔP to evaluate inspiratory effort.

Fever of unknown origin caused by infectious diseases in the era of migrant and refugee crisis.

Concern exists in Europe about the possibility of importation of infectious diseases due to the recent influx of migrants and refugees after 2011. In this retrospective 6-year study, we examined the epidemiology of fever of unknown origin (FUO) in Greece over the past years. Forty-eight patients with classical FUO were included. The proportion of infectious causes of FUO (29.2%) was similar to previous studies in Greece and all infections were endemic to the area. Disease-related mortality was 12.5% and no deaths due to infection were recorded. In conclusion, none of the diagnosed infectious causes of FUO raised concerns about the possibility of imported diseases or pathogens. These results re-inforce the perception that migrants and refugees are not carriers of communicable diseases that can cause public health problems to European countries.

Validation of a Proposed Algorithm for Assistance Titration During Proportional Assist Ventilation With Load-Adjustable Gain Factors.

BACKGROUND: The present study aimed to validate a recently proposed algorithm for assistance titration during proportional assist ventilation with load-adjustable gain factors, based on a noninvasive estimation of maximum inspiratory pressure (peak Pmus) and inspiratory effort (pressure-time product [PTP] peak Pmus). METHODS: Retrospective analysis of the recordings obtained from 26 subjects ventilated on proportional assist ventilation with load-adjustable gain factors under different conditions, each considered as an experimental case. The estimated inspiratory output (peak Pmus) and effort (PTP-peak Pmus) were compared with the actual-determined by the measurement of transdiaphragmatic pressure- and the derived PTP. Validation of the algorithm was performed by assessing the accuracy of peak Pmus in predicting the actual inspiratory muscle effort and indicating the appropriate level of assist. RESULTS: In the 63 experimental cases analyzed, a limited agreement was observed between the estimated and the actual inspiratory muscle pressure (-11 to 10 cm H2O) and effort (-82 to 125 cm H2O × s/min). The sensitivity and specificity of peak Pmus to predict the range of the actual inspiratory effort was 81.2% and 58.1%, respectively. In 49% of experimental cases, the level of assist indicated by the algorithm differed from that indicated by the transdiaphragmatic pressure and PTP. CONCLUSIONS: The proposed algorithm had limited accuracy in estimating inspiratory muscle effort and with indicating the appropriate level of assist.

Zika virus infection in a newly married Greek couple.

Zika virus (ZIKV) is a member of the Flaviviridae family causing asymptomatic or mildly symptomatic infections with fever, rash, arthralgia and headache. It is transmitted by the Aedes species mosquitoes and also sexually and transplacentally, and has been recently associated with congenital neurologic birth defects in South and Central America. We report the case of a newly married couple from Greece who travelled to Cuba for their honeymoon and developed mild symptoms consistent with arboviral infection. After returning to Greece, they were found to have been infected by Zika virus during their honeymoon. These are the first two cases of Zika virus infection in Greece, the southeastern border of Europe, denoting that Zika virus infection poses a threat for public health worldwide, since returning travelers could be asymptomatic carriers of the virus, not only leading to risk of neurologic birth defects for their offspring but also the real risk of transmission of the virus in their country by local Aedes mosquitoes.

An Unexpected Cause of Bradycardia in a Patient with Bacterial Meningitis.

Sinus bradycardia which is a sinus rhythm with a resting heart rate of less than 60 bpm is caused by intrinsic cardiac disorders like sick sinus syndrome or inferior myocardial infarction, metabolic and environmental causes (such as hypothyroidism and electrolyte disorders), medications (such as beta-blockers and amiodarone), infection (such as myocarditis), increased intracranial pressure, and toxic exposure, while it can sometimes be a normal phenomenon, especially during sleep, in athletes, and during pregnancy. Symptomatic sinus bradycardia should warrant a thorough work-up in order to identify any reversible causes; otherwise, placement of a permanent pacemaker could be needed. We present the case of a patient who was admitted due to confusion and fever and was found to have pneumococcal meningitis and bacteremia, and during his hospital stay he developed symptomatic sinus bradycardia that was of intractable cause and persistent. Placement of a permanent pacemaker was chosen until the night staff of the hospital discovered by chance the neglected cause of his bradycardia.

Clinical characteristics, microbiology and outcomes of external ventricular drainage-associated infections: The importance of active treatment.

Data concerning clinical characteristics, microbiology, treatment and outcomes of external ventricular drainage-associated infections (EVDAI) are limited. All hospitalized patients with EVDAI in a University Hospital between January 2009 and December 2015 were retrospective recorded. Only the first episode per patient was included. An antibiotic was considered "active" when its pharmacokinetic properties were appropriate for EVDAI and the implicated microorganism was in vitro susceptible. During the 7-year study period, 36 EVDAI were identified. Median patient age was 53years and 23 (63.9%) were male. Catheter types were intraventricular (70.6%) and lumbar (29.4%). Median catheterization duration before infection was 14days. Gram-negative bacteria (GNB) predominated (57.9%), followed by gram-positives (36.8%) and fungi (5.3%). Administered antibiotics were considered "active" in 69.4% of empirical and in 86.1% of definitive treatment regimens. In 10 infections, intraventricular/intrathecal (IVT) antibiotics were administered. Eleven patients died (30.6%) during hospitalization. Patients who died had higher rates of EVDAI by GNB (p=0.011) and higher rates of treatment with intravenous colistin (p=0.019 for empirical and p=0.006 for definitive colistin). Compared to EVDAI by other pathogens, patients with EVDAI by GNB had longer catheter-days before infection (p<0.001) and higher mortality (p=0.011). In our study, GNB were a frequent cause of EVDAI, and were related with high rates of inactive treatment and mortality. Intravenous colistin alone is not effective and treatment should include IVT antibiotics and intravenous antibiotics that achieve adequate CSF levels.

Immunohistochemical expression of endoglin offers a reliable estimation of bone marrow neoangiogenesis in multiple myeloma.

PURPOSE: The aim of the present study was to evaluate CD105 tissue marker in the bone marrow (BM) of multiple myeloma (MM) patients. CD105 was evaluated using immunohistochemical method. An effort was made to correlate this marker with BM microvascular density (MVD) along with other known markers of angiogenesis in order to evaluate its clinical significance. METHODS: BM MVD was estimated by CD31. CD105 in BM was estimated by immunohistochemical method in 54 newly diagnosed patients with MM. Circulating levels of known angiogenic factors such as basic fibroblast growth factor (b-FGF) and soluble CD105 (sCD105) were measured by ELISA in the same group of patients. All these factors were also measured in 20 age- and sex-matched healthy controls. RESULTS: We found that CD105 MVD, along with the expected CD31 MVD, and serum levels of sCD105 and bFGF were increased, also in parallel with disease stage, and all were decreased after effective treatment. Moreover, CD105 MVD correlated with all the aforementioned markers of angiogenesis. CONCLUSIONS: Our results indicated that CD105 MVD is following the behavior of CD31 MVD in MM, suggesting being a valid marker of BM neoangiogenesis in MM. Its prognostic impact remains to be proven.