Unexpected death of a ventilator-dependent amyotrophic lateral sclerosis patient

Background: Amyotrophic lateral sclerosis (ALS) is a fatal, progressive, neurodegenerative disease and most patients affected die of respiratory compromise and/or pneumonia within 2â3 years of diagnosis. As ALS progresses, ventilator assistance is required. In the end stages of the disease, patients suffer from respiratory failure and may become ventilator-dependent. Deaths due to malfunction of mechanical ventilators are reported but there are very few forensic autopsy records. We report the case of a 69-year-old ALS female ventilator-dependent, trachostomised patient who was found dead by her husband, with the ventilator in âstand-byâ mode. Method: A forensic autopsy was performed. Samples of internal organs were taken for histological and toxicological examination. The ventilator internal memory was also analysed and tested in order to find possible malfunction. Results: Gross examination did not reveal any sign of trauma but showed brain and lung congestion. Pulmonary histological examination revealed thickening of peribronchial interstitial space, alveolar over-distension, break of inter-alveolar walls and diffuse alveolar haemorrhages. Focal microhemorrhages were also detected in other organs. Analysis of the ventilator internal memory showed that during the night of death, there had been several voltage drops. Specific tests revealed malfunction of the internal battery which was unable to provide the necessary voltage, as a consequence the ventilator switched off, stopping ventilation. Battery malfunction reduced the volume of the ventilator alarm, which was not heard by the caregiver. Conclusion: Histological pattern, with acute pulmonary emphysema and focal polivisceral haemorrhages, is strongly suggestive of a death due to âacuteâ asphyxia. The authors also discuss the need for strict supervision and follow up of these ventilatory dependent patients and their devices. Resumo: Introdução: A Esclerose Lateral Amiotrófica (ELA) é uma doença fatal, progressiva e neurodegenerativa e a maioria dos doentes afectados morrerão de falha respiratória e/ou pneumonia 2 ou 3 anos após o diagnóstico. à medida que a ELA progride torna-se necessária a assistência ventilatória. Nos estágios finais da doença, os doentes sofrem de insuficiência respiratória e podem tornar-se dependentes do ventilador. São conhecidas mortes devido ao mau funcionamento de ventiladores mecânicos mas existem poucos registos forenses de tal situação. Relatamos o caso de uma doente de 69 anos com ELA, traqueostomizada e dependente do ventilador, que foi encontrada morta pelo seu marido com o ventilador em modo de espera («stand-by»). Método: Foi realizada uma autópsia forense. Foram recolhidas amostras dos órgãos internos para exame toxicológico e histológico. A memória interna do ventilador foi também analisada e testada de modo a descobrir uma possível avaria. Resultados: O exame macroscópico não revelou qualquer sinal de trauma mas indicou congestão cerebral e pulmonar. O exame pulmonar histológico revelou o espessamento do espaço intersticial peribrônquico, sobredistensão alveolar, quebra de paredes interalveolares e hemorragias alveolares difusas. Foram detetadas micro-hemorragias focais noutros órgãos. A análise da memória interna do ventilador mostrou que, durante a noite da morte, houve diversas quedas de tensão. Testes específicos revelaram o mau funcionamento da bateria interna que não conseguiu fornecer a tensão necessária, consequentemente o ventilador desligou-se, parando a ventilação. O mau funcionamento da bateria reduziu o volume do alarme do ventilador, que não foi ouvido pelo prestador de cuidados. Conclusão: O padrão histológico, com enfisema pulmonar agudo e hemorragias focais poliviscerais, é fortemente indicador de morte devido a asfixia «aguda». Os autores discutem também a necessidade de uma supervisão rigorosa e seguimento destes doentes dependentes do ventilador e dos seus equipamentos. Keywords: Amyotrophic lateral sclerosis, Acute respiratory failure, Home mechanical ventilation, Palavras-chave: Esclerose lateral amiotrófica, Insuficiência respiratória aguda, Ventilação mecânica doméstic

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Inspiratory muscle workload due to dynamic intrinsic PEEP in stable COPD patients: effects of two different settings of non-invasive pressure-support ventilation.

BACKGROUND: In severe stable hypercapnic COPD patients the amount of pressure time product (PTP) spent to counterbalance their dynamic intrinsic positive end expiratory pressure (PEEPi,dyn) is high: no data are available on the best setting of non invasive pressure support ventilation (NPSV) to reduce the inspiratory muscle workload due to PEEPi,dyn. METHODS: The objectives of this randomised controlled physiological study were: 1. To measure the inspiratory muscle workload due to PEEPi,dyn 2. To measure the effects on this parameter of two settings of NPSV in stable COPD patients with chronic hypercapnia admitted in a Pulmonary Division of two Rehabilitation Centers. Twenty-three stable COPD patients with chronic hypercapnia on domiciliary nocturnal NPSV for 30 +/- 20 months were submitted to an evaluation of breathing pattern, PEEPi,dyn, inspiratory muscle workload and its partitioning during both assisted and unassisted ventilation. Two settings of NPSV were randomly applied for 30 minutes each: i- "at patient's comfort" (C): Inspiratory pressure support (IPS) was the maximal tolerated pressure able to reduce awake PaCO2 with the addition of a pre-set level of external PEEP (PEEPe); ii- "physiological setting" (PH): the level of IPS able to achieve a > 40% and < 90% decrease in transdiaphragmatic pressure in comparison to spontaneous breathing (SB). A PEEPe level able to reduce PEEPi,dyn by at least 50% was added. RESULTS: During SB the tidal diaphragmatic pressure-time product (PTPdi/b) was 17.62 +/- 7.22 cmH2O*sec, the component due to PEEPi,dyn (PTPdiPEEPi,dyn) being 38 +/- 17% (range: 16-65%). Compared to SB,PTPdiPEEPi,dyn was reduced significantly with both settings, the reduction being greater with PH compared to C. CONCLUSIONS: In conclusion in severe COPD patients with chronic hypercapnia the inspiratory muscle workload due to PEEPidyn is high and is reduced by NPSV at a greater extent when ventilator setting is tailored to patient's mechanics

Pulmonary tuberculosis in intensive care setting, with a focus on the use of severity scores, a multinational collaborative systematic review.

BACKGROUND AND AIM: Tuberculosis (TB) is associated with a high mortality in the intensive care unit (ICU), especially in subjects with Acute Respiratory Distress Syndrome (ARDS) requiring mechanical ventilation. Despite its global burden on morbidity and mortality, TB is an uncommon cause of ICU admission, however mortality is disproportionate to the advances in diagnosis and treatment made. Herein we report a systematic review of published studies. METHODS: Our Literature search was conducted to identify studies on outcomes of individuals with TB admitted to ICU. We report and review in-hospital mortality, predictors of poorer outcomes, usefulness of severity scoring systems and potential benefits of intravenous antibiotics. Searches from Pubmed, Embase, Cochrane and Medline were conducted from inception to March 2020. Only literature in English was included. RESULTS: Out of 529 potentially relevant articles, 17 were included. Mortality across all studies ranged from 29-95% with an average of 52.9%. All severity scores underestimated average mortality. The most common indication for ICU admission was acute respiratory failure (36.3%). Negative predictors of outcome included hospital acquired infections, need of mechanical ventilation and vasopressors, delay in initiation of anti-TB treatment, more than one organ failure and a higher severity score. Low income, high incidence countries showed a 23.4% higher mortality rate compared to high income, low TB incidence countries. CONCLUSION: Mortality in individuals with TB admitted to ICU is high. Earlier detection and treatment initiation is needed

Morphological, Gene, and Hormonal Changes in Gonads and In-Creased Micrococcal Nuclease Accessibility of Sperm Chromatin Induced by Mercury

Mercury is one of the most dangerous environmental pollutants. In this work, we analysed the effects of exposure of Mytilus galloprovincialis to 1, 10 and 100 pM HgCl2 for 24 h on the gonadal morphology and on the expression level of three stress genes: mt10, hsp70 and πgst. In this tissue we also evaluated the level of steroidogenic enzymes 3β-HSD and 17β-HSD and the expression of PL protein genes. Finally, we determined difference in sperm chromatin accessibility to micrococcal nuclease. We found alterations in gonadal morphology especially after exposure to 10 and 100 pM HgCl2 and hypo-expression of the three stress genes, particularly for hsp70. Furthermore, decreased labelling with both 3β-HSD and 17β-HSD antibodies was observed following exposure to 1 and 10 pM HgCl2 and complete absence at 100 pM HgCl2 exposure. Gonads of mussels exposed to all HgCl2 doses showed decreased expression of PL protein genes especially for PLIII. Finally, micrococcal nuclease digestions showed that all doses of HgCl2 exposure resulted in increased sperm chromatin accessibility to this enzyme, indicative of improper sperm chromatin structure. All of these changes provide preliminary data of the potential toxicity of mercury on the reproductive health of this mussel

Effect of pulmonary rehabilitation on heart rate recovery in adult individuals with asthma or chronic obstructive pulmonary disease

Introduction: Heart rate recovery (HRR) after exercise is a marker of disease severity and prognosis in cardiovascular and respiratory disorders. More than 30% of adult individuals with asthma may show a slow HRR. Pulmonary rehabilitation improves exercise capacity in individuals with asthma or chronic obstructive pulmonary disease (COPD). Aim: The study aimed to evaluate the effect of pulmonary rehabilitation on HRR in individuals with asthma as compared to those with COPD. Methods: Retrospective analysis of HRR one minute after the six-minute walking test (6MWT) was performed before and after an exercise training program. The COPD Assessment Test (CAT), Barthel Index-Dyspnea (BI-D), Medical Research Council (MRC) score for dyspnea, and the Five-Times-Sit-to-Stand test (5STS) were also assessed as secondary outcome measures. Results: Slow HRR prevalence was significantly lower in individuals with asthma than with COPD (29.1 vs. 46.7%, respectively: p = 0.003). Post-program HRR did not change in more than 70% of individuals in either population and improved in 16% of both populations, whereas it actually worsened in 12 and 10% of individuals with asthma and COPD, respectively. The outcome measures significantly improved in both populations, irrespective of baseline HRR. Conclusion: In individuals with asthma or COPD, exercise training does not significantly improve HRR

Lung and respiratory muscle function at discharge from a respiratory intensive care unit

Background. The purpose of this prospective observational study was to describe lung and respiratory muscle function at Respiratory Intensive Care Unit (RICU) discharge after a severe exacerbation of Chronic Obstructive Pulmonary Disease (COPD). Methods. The study was conducted in 42 consecutive COPD patients in whom arterial blood gases, dynamic and static lung volumes, maximal inspiratory pressure (MIP) were assessed at discharge from the RICU and compared with values measured 6 months previously when they were in a stable state. The same measurements were performed at 6-month interval in 42 comparable stable COPD patients not requiring any hospitalisation for at least 6 months used as controls. Results. 24% of patients in the study group were discharged with hypercapnia whereas they were normocapnic before the acute episode. Compared to prior to exacerbation, patients of study group showed a significant worsening in mean values of PaCO2 (p=0.005), MIP (p=0.005) and FEV1 (p=0.041). Predefined criteria of worsening in PaCO2, MIP and FEV1 were observed in 47%, 33% and 28% of patients in study respectively. Neither lung nor respiratory muscle function in last stable state did predict post RICU functional worsening. In a period of 6 months controls showed no change in the studied parameters. Conclusions. After a severe acute exacerbation requiring admission to a RICU and immediately before discharge 1) a large proportion of COPD patients still show preserved lung and respiratory muscle function 2) more than one third of them would require further care and rehabilitative attempts to restore functional derangements

Tracheostomy in patients with long-term mechanical ventilation: a survey.

BACKGROUND: Tracheostomy is increasingly performed in intensive care units (ICU), with many patients transferred to respiratory ICU (RICU). Indications/timing for closing tracheostomy are discussed. AIM AND METHOD: We report results of a one-year survey evaluating: 1) clinical characteristics, types of tracheostomy, complications in patients admitted to Italian RICU in 2006; 2) clinical criteria and systems for performing decannulation, and outcome of patients undergoing tracheostomy (number decannulated; number non-decannulated/non-ventilated; number non-decannulated/ventilated; dead/lost patients). RESULTS: 22/32 RICUs replied. There were 846 admissions of 719 patients (Mean age 64,3 (+/-14.2) years, 489 (68%) males). Causes of admission were: acute respiratory failure with underlying chronic co-morbidities 176 (24.4%); exacerbation of Chronic Obstructive Pulmonary Disease 222 (34.4%); neuromuscular diseases 200 (27.8%); surgical patients 77 (10.7%); thoracic dysmorphism 28 (3.8%); obstructive sleep apnea syndrome 16 (2.2%). Percutaneous tracheostomies were 65.9%. Major complications after tracheostomy were 2%. 427 tracheostomies were evaluated for decannulation: 96 (22.5%) were closed; 175 patients (41%) were discharged with home mechanical ventilation; 114 patients (26.5%) maintained the tracheostomy despite weaning from mechanical ventilation and 42 patients (10%) died or lost. The clinical criteria chosen for decannulation were: stability of respiratory conditions, effective cough, underlying diseases and ability to swallow. The systems for evaluating feasibility of decannulation were: closure of tracheostomy tube; laryngo-tracheoscopy; use of tracheal button and down-sizing. CONCLUSIONS: There were few major complications of tracheostomy. A substantial proportion of patients maintain the tracheostomy despite not requiring mechanical ventilation. There was no agreement on indications and systems for closing tracheostom