Inspiratory Effort and Respiratory Mechanics in Patients with Acute Exacerbation of Idiopathic Pulmonary fibrosis: A Preliminary Matched Control Study.

BACKGROUND: Patients with acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) may experience severe acute respiratory failure, even requiring ventilatory assistance. Physiological data on lung mechanics during these events are lacking. METHODS: Patients with AE-IPF admitted to Respiratory Intensive Care Unit to receive non-invasive ventilation (NIV) were retrospectively analyzed. Esophageal pressure swing (ΔPes) and respiratory mechanics before and after 2 hours of NIV were collected as primary outcome. The correlation between positive end-expiratory pressure (PEEP) levels and changes of in dynamic compliance (dynCRS) and PaO2/FiO2 ratio was assessed. Further, an exploratory comparison with a historical cohort of ARDS patients matched 1:1 by age, sequential organ failure assessment score, body mass index and PaO2/FiO2 level was performed. RESULTS: At baseline, AE-IPF patients presented a high respiratory drive activation with ΔPes = 27 (21-34) cmH2O, respiratory rate (RR) = 34 (30-39) bpm and minute ventilation (VE) = 21 (20-26) L/min. Two hours after NIV application, ΔPes, RR and VE values showed a significant reduction (16 [14-24] cmH2O, p<0.0001, 27 [25-30] bpm, p=0.001, and 18 [17-20] L/min, p=0.003, respectively) while no significant change was found in dynamic transpulmonary pressure, expiratory tidal volume (Vte), dynCRS and dynamic mechanical power. PEEP levels negatively correlated with PaO2/FiO2 ratio and dynCRS (r=-0.67, p=0.03 and r=-0.27, p=0.4, respectively). When compared to AE-IPF, ARDS patients presented lower baseline ΔPes, RR, VE and dynamic mechanical power. Differently from AE-IPF, in ARDS both Vte and dynCRS increased significantly following NIV (p=0.01 and p=0.004 respectively) with PEEP levels directly associated with PaO2/FiO2 ratio and dynCRS (r=0.24, p=0.5 and r=0.65, p=0.04, respectively). CONCLUSIONS: In this study, patients with AE-IPF showed a high inspiratory effort, whose intensity was reduced by NIV application without a significant improvement in respiratory mechanics. In an exploratory analysis, AE-IPF patients showed a different mechanical behavior under spontaneous unassisted and assisted breathing compared with ARDS patients of similar severity.

Association between respiratory distress time and invasive mechanical ventilation in COVID-19 patients: A multicentre regional cohort study.

AIM: To determine whether the duration of respiratory distress symptoms in severe COVID-19 pneumonia affects the need for invasive mechanical ventilation and clinical outcomes. MATERIALS AND METHODS: An observational multicentre cohort study of patients hospitalised in five COVID-19-designated ICUs of the University Hospitals of Emilia-Romagna Region. Patients included were adults with pneumonia due to SARS-CoV-2 with PaO2/FiO2 ratio <300 mmHg, respiratory distress symptoms, and need for mechanical ventilation (invasive or non-invasive). Exclusion criteria were an uncertain time of respiratory distress, end-of-life decision, and mechanical respiratory support before hospital admission. MEASUREMENTS AND MAIN RESULTS: We analysed 171 patients stratified into tertiles according to respiratory distress duration (distress time, DT) before application of mechanical ventilation support. The rate of patients requiring invasive mechanical ventilation was significantly different (p < 0.001) among the tertiles: 17/57 patients in the shortest duration, 29/57 in the intermediate duration, and 40/57 in the longest duration. The respiratory distress time significantly increased the risk of invasive ventilation in the univariate analysis (OR 5.5 [CI 2.48-12.35], p = 0.003). Multivariable regression analysis confirmed this association (OR 10.7 [CI 2.89-39.41], p < 0.001). Clinical outcomes (mortality and hospital stay) did not show significant differences between DT tertiles. DISCUSSION: Albeit preliminary and retrospective, our data raised the hypothesis that the duration of respiratory distress symptoms may play a role in COVID-19 patients' need for invasive mechanical ventilation. Furthermore, our observations suggested that specific strategies may be directed towards identifying and managing early symptoms of respiratory distress, regardless of the levels of hypoxemia and the severity of the dyspnoea itself.

Acute renal failure and renal replacement therapy in the postoperative period of orthotopic liver transplant patients versus nonelective abdominal surgery patients.

Acute renal failure (ARF) often complicates the postoperative period of patients undergoing orthotopic liver transplantation (OLT); it is habitually associated with high mortality rates. Similarly, patients undergoing major nonelective abdominal surgery are prone to ARF because of their frequent preexistent morbidities, abdominal sepsis, and needed for extended surgical procedures. The aim of this study was to evaluate the incidence of ARF and use of renal replacement therapy (RRT) among OLT versus nonelective abdominal surgery patients and associations with clinical outcomes. We studied all the patients admitted to a surgical intensive care unit (ICU) from January 2008 to December 2009 after OLT or nonelective abdominal surgery. The inclusion criteria were an ICU stay of at least 48 hours and without prior end-stage renal failure. OLT patients (n=84) were younger and less severly ill than surgery patients (n=60). ARF occurrence was lower among the OLT (29%) than the surgery group (47%) requiring RRT in 71% and 53% of patients due to ARF, respectively. The ICU mortality of ARF patients in both groups (29% OLT and 51% surgery) were greater than among subjects without ARF (2% and 6%). The occurrence of ARF is common among these two patient groups, and associated with increased risk of death among in surgery (+45%) versus in OLT (+27%) patients.

Use of recombinant factor IX and thromboelastography in a patient with hemophilia B undergoing liver transplantation: a case report.

Hemophilia B is a congenital recessive disorder caused by deficiency of coagulation factor IX (FIX). Surgical procedures can be performed in patients with hemophilia using high-purity and/or recombinant FIX, which has been shown to be safe and effective in surgical hemostasis. Liver transplantation is the only potentially curative treatment available for these patients, providing a long-term phenotypic cure for hemophilia. End-stage liver disease together with hemophilia exposes patients to greater risks of bleeding complications during the perioperative period with consequent difficulties in managing coagulopathy. The limited experiences reported by different investigators and the various strategies for clotting factor replacement make it difficult to define a single approach with respect to the optimal dose and method of administering FIX to achieve perioperative hemostasis. The limits of plasma-based coagulation tests--prothrombin time, activated partial thromboplastin time--have made thromboelastography a valid alternative in this kind of surgery. It has been demonstrated to be a useful tool for real-time analysis of clot formation using a whole-blood assay format. Further, it accurately illustrates the clinical effects of procoagulant or anticoagulant interventions. In this article, we have described the usefulness of thromboelastography to monitor the ability of high-purity FIX supplementation to restore a normal coagulation state and to guide the perioperative administration of blood products in a successful orthotopic liver transplantation in a hemophilic patient with deficiencies of factors IX and X, presenting with hepatitis C virus-related cirrhosis and hepatocellular carcinoma.

Maturation of cerebral electrical activity and development of cortical folding in young very preterm infants.

OBJECTIVE: The aim of this study was to examine the relationship between cortical development and cerebral electrical activity at early gestational ages. METHODS: We obtained EEGs (7.2+/-3.8 days) and MR brain images (3.2+/-2.9 days) after birth in 17<30 week gestation infants without evidence of focal brain injury The EEGs were assessed for discontinuity and characteristic maturational features (delta brush, occipital and temporal sawtooth); cortical development was quantified from MR scans using a specially designed computer programme to measure cortical folding. RESULTS: The inter-burst interval shortened and cortical folding increased with increasing post-menstrual age (PMA). In contrast, the minimum duration of bursts was independent of PMA and cortical folding. Delta brush (8-20 Hz activities) was seen at all PMAs; temporal and occipital sawtooth activities were always more prominent than delta brush but were seen less frequently with increasing PMA and complexity of cortical folding. CONCLUSION: There was a positive correlation between some but not all maturational features of the preterm neonatal EEG and the complexity of whole brain cortical folding and PMA. These relationships were strong for the inter-burst interval, a global measure of maturation, but not strongly seen for regional features such as occipital and temporal sawtooth within this gestational age range. SIGNIFICANCE: Combining neurophysiological examination with detailed neuroimaging gives insights into developmental changes occurring in the very preterm brains and suggests further comparative studies focusing on measures of focal brain development at different gestational ages.

Auditory attention at the onset of West syndrome: correlation with EEG patterns and visual function.

At the onset of West syndrome a specific impairment of visual function has been clearly demonstrated, while other aspects of sensorial development, and in particular of the auditory function, have been less studied. The aim of this study was to evaluate auditory function and orienting responses at the onset of West syndrome, and to relate the results with EEG patterns, visual function and neurodevelopmental competence. A prospective multicentric study was performed on 25 successively enrolled infants with West syndrome; all the patients underwent a full clinical assessment, including MRI and video-EEG, visual function and auditory orienting responses (AORs) as well as Griffiths' developmental scales. The whole assessment performed at the onset of spasms (T0) was repeated after two months (T1). AORs resulted significantly impaired both at T0 and T1. At the onset of spasms a highly significant relationship of auditory attention with visual function and neurodevelopmental competence was shown in both cryptogenic and symptomatic forms, but it was no longer present after two months. Our results may suggest a possible pervasive effect of the epileptic disorder on sensory processing, associated to a deficit of neurodevelopment. Although we failed to show a significant correlation between auditory orienting responses and EEG patterns, some evidence seems to support at least partially an influence of the epileptic disorder per se on the genesis of the sensorial impairment. A longer follow up and a larger cohort will be useful for a better clarification of these findings.

Distribution of sleep and wakefulness EEG patterns in 24-h recordings of preterm and full-term newborns.

The aim of this study was to evaluate the organisation of EEG patterns in 24-h recordings of preterm and near-term neonates. In particular, the distribution of the different EEG codes at different postmenstrual ages (PMA) and the variations of sleep-related EEG pattern organisation was studied, during day (8.00 a.m.-8.00 p.m.) and night (8.00 p.m.-8.00 a.m.) time. The age of appearance of different neonatal EEG patterns, previously described in literature for short lasting records, was confirmed in this 24-h study. The medium-voltage continuous EEG pattern (pattern "3") was less represented approaching term age, in coincidence with the appearance of the two low-voltage continuous patterns ("1" and "2"), which are also related to active sleep and wakefulness. Discontinuous pattern ("7") was also less represented with age, but in day-time only. The percentage of time occupied by this pattern, related to quiet sleep, was significantly higher during day-time hours, than at night.

Visual function and EEG reactivity in infants with perinatal brain lesions at 1 year.

The aim of this study was to examine the correlation between EEG, visual, and brain MRI findings in 19 term infants with perinatal brain lesions. All 19 had their visual acuity and visual fields assessed and had an EEG and a brain MRI performed at 1 year of age. Four of the five infants with normal optic radiations and occipital cortices on MRI had normal vision. Involvement of optic radiations and occipital cortices was only associated with visual abnormalities in eight of 14 infants. The correlation between visual abnormalities and EEG findings was stronger. All infants with a completely normal EEG from the posterior regions had normal vision and all those with an EEG non-reactive to eye closure had visual abnormalities, irrespective of MRI data. A reactive EEG with other abnormal features (such as spikes, rapid or slow activities) was accompanied by abnormal vision in five of eight participants. Results suggest that there is a better correlation between visual function and EEG activity than between visual function and involvement of the classical visual areas of the occipital cortex and optic radiations on brain MRI at 1 year of age.

Combined use of electroencephalogram and magnetic resonance imaging in full-term neonates with acute encephalopathy.

OBJECTIVE: The electroencephalogram (EEG) is widely used in full-term infants with acute neonatal encephalopathy, and its prognostic value has been confirmed by several studies. Magnetic resonance imaging (MRI) of the brain has also been applied in these patients, and increasing numbers of reports affirm its prognostic reliability. The aim of this study has been to investigate the correlation between an early EEG and MRI findings in infants with acute neonatal encephalopathy and to assess the prognostic value of a combination of EEG and MRI findings. PARTICIPANTS AND METHODS: Twenty-five full-term infants had an EEG recorded within the first 72 hours after birth and a neonatal brain MRI scan after the end of the first week. RESULTS: Both EEG and MRI were predictive of outcome. A normal MRI was always associated with normal EEG background activity and normal outcome and severe abnormalities on MRI with marked EEG abnormalities and an abnormal outcome. When the MRI showed moderate abnormalities, the EEG in all cases but one identified patients with normal and abnormal outcome.EEG, MRI, HIE, neurodevelopment.

Activity patterns assessed throughout 24-hour recordings in preterm and near term infants.

The motility of 10 low-risk infants, aged between 34 and 40 weeks of postmenstrual age, has been continuously recorded for 24 h. Four codes were distinguished: code 1 (absence of motility or occasional occurrence of startles), code 2 (presence of small general or isolated body movements, startles, smiles, grimaces, and other facial activity), code 3 (forceful and prolonged general movements, startles, and stretches), code 4 (vigorous and abrupt general body movements accompanied by crying). Changes with age concern mainly the increase of the duration of code 1 (quiescence) episodes. Confrontation between day and night showed higher levels of motility during the night than during the day. The last weeks before term represent a time for increase in the ability to sustain a quiet behavior and to reorganize day-night motility distribution.

[Role of neurologic assessment in the evaluation and prognosis of full-term newborns with asphyxia]. / Ruolo della semeiotica neurologica nella valutazione e nella prognosi del neonato a termine asfittico.

Hypoxic-ischaemic encephalopathy, the clinical neurological syndrome that follows birth asphyxia, is one of the main causes of neurological sequelae in term newborns. Despite the advent of new imaging and neurophysiological techniques in the last two decades, the value of the neurological assessment of the newborn has not been reduced. The possibility to perform easily serial neurological evaluations allows a detailed and non-invasive follow up of the early developmental processes, providing reliable prognostic information. In this paper we report our experience and a more general review of the literature on the prognostic value of the neurological assessment in term newborns with hypoxic-ischaemic encephalopathy.

Occipital sawtooth: a physiological EEG pattern in very premature infants.

OBJECTIVE: To evaluate EEG maturational features in preterm infants below 27 weeks postmenstrual age. METHODS: EEGs recorded from 5 preterm infants (postmenstrual age 24-26 weeks) were examined and selected maturational features were scored and quantified. The five infants also had serial cranial ultrasound scans (US) and magnetic resonance images of the brain within the first weeks after birth. RESULTS: Background activity was markedly discontinuous in all patients and very variable. Temporal sawtooths occurred but less frequently than in older preterm infants. All 5 infants also showed a particular novel feature, characterized by rhythmic, regularly shaped, medium-high amplitude 4-7 Hz activities, lasting 0.5-3 s and located in the occipital regions. This pattern was symmetrical but sometimes asynchronous. CONCLUSIONS: Occipital sawtooth, so called because it shares shape and frequency with temporal sawtooth but has an occipital localisation, constitutes a physiological EEG pattern characteristic of premature infants between 24 and 26 weeks of postmenstrual age.

Electroencephalography in infants with periventricular leukomalacia: prognostic features at preterm and term age.

Cystic periventricular leukomalacia represents the most severe white-matter lesion in preterm infants and its occurrence accounts for most cases of neurologic impairment in these subjects. Electroencephalographic (EEG) findings and their prognostic value in relation to motor and cognitive outcome were investigated in a group of preterm infants affected by different degrees of cystic periventricular leukomalacia. EEG recordings were carried out in the early postnatal period (first 2 weeks of life) on 24 infants and at term age on 29. In the early postnatal period, background EEG abnormalities ("dysmaturity") were significantly more apparent in affected infants than in a control group, and, among infants with cystic periventricular leukomalacia, this parameter related to the occurrence of cerebral palsy; moreover, at the same age, the incidence of abnormal EEG transients seemed to show a correlation with cognitive outcome. At term age, these latter abnormalities were significantly more apparent in neonates with cystic periventricular leukomalacia than in control subjects, but they did not show any prognostic value. In conclusion, these data indicate that, during the early postnatal period, the EEG is a useful diagnostic and prognostic tool for preterm infants with white-matter lesions, whereas at term age, the role of EEG tracings appears secondary.

Constantly discontinuous EEG patterns in full-term neonates with hypoxic-ischaemic encephalopathy.

OBJECTIVES: Selected EEG features were evaluated in 21 constantly discontinuous tracings recorded on the same number of full-term neonates with hypoxic-ischaemic encephalopathy. METHODS: The tracings were examined without using interval amplitude as the basis for distinguishing between burst-suppression and nonburst-suppression patterns. RESULTS: The results were related to outcomes and other clinical parameters (severity of hypoxic-ischaemic encephalopathy, pO2 levels and drug intake). CONCLUSIONS: Features defining the grade of EEG discontinuity (i.e. maximum interval duration, minimum burst duration and interval amplitude) significantly related to outcome and, in most cases, to the grade of hypoxic-ischaemic encephalopathy. Other features (amplitude of slow waves within the burst and incidence of abnormal EEG transients) related to PO2 levels. The consumption of anticonvulsant drugs increased EEG discontinuity, but this effect did not seem dose-related. Finally, the persistence of a constantly discontinuous EEG pattern after the first week of life is a sign of unfavourable prognosis. In full-term neonates with hypoxic-ischaemic encephalopathy quantitative analysis of all constantly discontinuous EEGs seems more useful than only describing burst-suppression patterns on the basis of interval amplitude.

Electroclinical correlation in neonatal seizures.

A dissociation between clinical and electroencephalographic phenomena is often observable in neonatal seizures. This finding raises important questions, including those related to the management of these patients. Another characteristic of neonatal convulsions is represented by their increased tendency towards status epilepticus. In order to examine the electroclinical correlation and its possible relationship to the occurrence of status epilepticus, recorded video-electroencephalograms of 17 newborns were submitted to detailed analysis. Time of onset, duration and other characteristics of all clinical and electrical events were noted. Five degrees of correlation were observed, from constant concurrence to complete dissociation. Examining the role of different parameters, it was observed that the incidence of electric discharges related significantly to the occurrence of electroclinical dissociation.

Electroencephalographic dysmaturity in preterm infants: a prognostic tool in the early postnatal period.

The aim of the study was to assess the prognostic value of maturational abnormalities in the electroencephalogram (EEG) of preterm infants. 63 subjects (mean gestational age: 32.7 weeks; range 28-34) were submitted to EEG recording within the first two weeks of life and subsequently followed up until at least 12 months of corrected age. Maturational features of background EEG were analysed and the occurrence of different degrees of maturational anomalies ("dysmaturity") was scored, according to standardised criteria. The results were compared to neurological outcome and to cranial ultrasound (US) findings. EEG maturational features significantly related to the outcome. When the EEG background activity was normal all but one patient showed a favourable outcome; the incidence of neurological sequelae became higher according to the degree of dysmaturity detected. However, some infants had a normal evolution, despite severe EEG dysmaturity in the early postnatal period. The correlation between EEG and US findings was low, although US also significantly related to the outcome. Background EEG maturational features seem to be a reliable prognostic tool in the early postnatal period of preterm infants, complementary to serial US scans.

Prognostic value of abnormal EEG transients in preterm and full-term neonates.

The prognostic value of abnormal EEG transients was investigated in 362 subjects submitted to EEG recording during the neonatal age and followed-up at least until the 12th month of corrected age. The incidence of negative and positive spikes and sharp waves, of rhythmic sharp theta and delta activities and of alpha discharges were evaluated by means of a quantitative score. These abnormal EEG transients appeared to be generally rare and even absent in a large number of subjects. In infants with normal outcome their incidence tends to increase from low postmenstrual ages towards term period. Full-term newborns with abnormal neurological outcome presented a significantly higher incidence of these transients. Preterm infants with unfavourable evolution showed a higher incidence only when submitted to EEG recording at around term age. However, no difference between subjects with normal and abnormal outcome was detected in preterm infants when evaluated at low postmenstrual ages. The hypothesis that at low postmenstrual ages brain damage might, on the one hand, give rise to abnormal transients and, on the other, alter the "capability' of manifesting them (together with other EEG maturational aspects), might explain these results.

Background EEG activity in preterm infants: correlation of outcome with selected maturational features.

The aim of this study is to identify normal EEG patterns of preterm infants, characteristic of early postmenstrual ages (PMAs). Quantitative features of EEG background activity have been examined in records from 83 preterm infants within the first 2 weeks of life at a PMA of 27-34 weeks. These subjects presented different cranial ultrasound findings and different outcomes. EEG quantitative data have been compared to the subsequent neurological evolution. We supposed that the features of EEG background activity which were associated with a favourable outcome should be considered as indexes of "normality" of the tracing for that specific PMA. At 27-30 weeks of PMA a high incidence of "temporal sawtooth," a particular rhythmic theta activity detectable in temporal regions, relates to a favourable evolution, therefore it can be assumed that this activity is a normal feature of EEG tracings at this age. On the contrary, a significant correlation between a high incidence of "temporal sawtooth" and an abnormal outcome is observable at 33-34 weeks and leads us to deduce that this pattern should disappear at this time. After 31 weeks other parameters (such as the incidence of 8-20 Hz activities, the length of the intervals and burst duration) show a significant correlation with the outcome.