Automatic versus manual pressure support reduction in the weaning of post-operative patients: a randomised controlled trial

Introduction Reduction of automatic pressure support based on a target respiratory frequency or mandatory rate ventilation (MRV) is available in the Taema-Horus ventilator for the weaning process in the intensive care unit (ICU) setting. We hypothesised that MRV is as effective as manual weaning in post-operative ICU patients. Methods There were 106 patients selected in the postoperative period in a prospective, randomised, controlled protocol. When the patients arrived at the ICU after surgery, they were randomly assigned to either: traditional weaning, consisting of the manual reduction of pressure support every 30 minutes, keeping the respiratory rate/tidal volume (RR/TV) below 80 L until 5 to 7 cmH(2)O of pressure support ventilation (PSV); or automatic weaning, referring to MRV set with a respiratory frequency target of 15 breaths per minute (the ventilator automatically decreased the PSV level by 1 cmH(2)O every four respiratory cycles, if the patient`s RR was less than 15 per minute). The primary endpoint of the study was the duration of the weaning process. Secondary endpoints were levels of pressure support, RR, TV (mL), RR/TV, positive end expiratory pressure levels, FiO(2) and SpO(2) required during the weaning process, the need for reintubation and the need for non-invasive ventilation in the 48 hours after extubation. Results In the intention to treat analysis there were no statistically significant differences between the 53 patients selected for each group regarding gender (p = 0.541), age (p = 0.585) and type of surgery (p = 0.172). Nineteen patients presented complications during the trial (4 in the PSV manual group and 15 in the MRV automatic group, p < 0.05). Nine patients in the automatic group did not adapt to the MRV mode. The mean +/- sd (standard deviation) duration of the weaning process was 221 +/- 192 for the manual group, and 271 +/- 369 minutes for the automatic group (p = 0.375). PSV levels were significantly higher in MRV compared with that of the PSV manual reduction (p < 0.05). Reintubation was not required in either group. Non-invasive ventilation was necessary for two patients, in the manual group after cardiac surgery (p = 0.51). Conclusions The duration of the automatic reduction of pressure support was similar to the manual one in the postoperative period in the ICU, but presented more complications, especially no adaptation to the MRV algorithm. Trial Registration Trial registration number: ISRCTN3745664

High success and low mortality rates with non-invasive ventilation in influenza A H1N1 patients in a tertiary hospital

<p>Abstract</p> <p>Background</p> <p>In 2009, an outbreak of respiratory illness caused by influenza A H1N1 virus occurred worldwide. Some patients required Intensive Care Unit (ICU) admission. The use of non-invasive ventilation (NIV) in these patients is controversial, as the aerosol dispersion may contaminate the environment and health-care co-workers.</p> <p>Methods</p> <p>Describe the respiratory profile, the mortality rate, and the benefit of using NIV in patients with confirmed diagnosis of influenza AH1N1 who were admitted in the ICU during the year 2009.</p> <p>Results</p> <p>A total of 1, 401 cases of influenza A H1N1 were confirmed in our hospital by real-time RT-PCR in 2009, and 20 patients were admitted to the ICU. The patients' ages ranged from 18 to 74 years (median of 42). Acute Respiratory Failure (ARF) was present in 70% of patients. The median Acute Physiology and Chronic Health Evaluation II score was 7 (range 7 to 25). Of the 14 patients who developed ARF, 85.7% needed NIV and 14% needed invasive MV at admission. Our success rate (41.6%) with NIV was higher than that described by others. The hospital mortality rate was 2.1%. When influenza A H1N1 arrived in Brazil, the disease was already on endemic alert in other countries. The population was already aware of the symptoms and the health-care system of the treatment. This allowed patients to be properly and promptly treated for influenza A H1N1, while health-care workers took protective measures to avoid contamination.</p> <p>Conclusion</p> <p>In our study we found a high success and low mortality rates with non-invasive ventilation in patients with influenza A H1N1.</p

Genome-Wide Association Study and Gene Expression Analysis Identifies CD84 as a Predictor of Response to Etanercept Therapy in Rheumatoid Arthritis

Anti-tumor necrosis factor alpha (anti-TNF) biologic therapy is a widely used treatment for rheumatoid arthritis (RA). It is unknown why some RA patients fail to respond adequately to anti-TNF therapy, which limits the development of clinical biomarkers to predict response or new drugs to target refractory cases. To understand the biological basis of response to anti-TNF therapy, we conducted a genome-wide association study (GWAS) meta-analysis of more than 2 million common variants in 2,706 RA patients from 13 different collections. Patients were treated with one of three anti-TNF medications: etanercept (n = 733), infliximab (n = 894), or adalimumab (n = 1,071). We identified a SNP (rs6427528) at the 1q23 locus that was associated with change in disease activity score (ΔDAS) in the etanercept subset of patients (P = 8×10-8), but not in the infliximab or adalimumab subsets (P>0.05). The SNP is predicted to disrupt transcription factor binding site motifs in the 3′ UTR of an immune-related gene, CD84, and the allele associated with better response to etanercept was associated with higher CD84 gene expression in peripheral blood mononuclear cells (P = 1×10-11 in 228 non-RA patients and P = 0.004 in 132 RA patients). Consistent with the genetic findings, higher CD84 gene expression correlated with lower cross-sectional DAS (P = 0.02, n = 210) and showed a non-significant trend for better ΔDAS in a subset of RA patients with gene expression data (n = 31, etanercept-treated). A small, multi-ethnic replication showed a non-significant trend towards an association among etanercept-treated RA patients of Portuguese ancestry (n = 139, P = 0.4), but no association among patients of Japanese ancestry (n = 151, P = 0.8). Our study demonstrates that an allele associated with response to etanercept therapy is also associated with CD84 gene expression, and further that CD84 expression correlates with disease activity. These findings support a model in which CD84 genotypes and/or expression may serve as a useful biomarker for response to etanercept treatment in RA patients of European ancestry. © 2013 Cui et al

Genetics of rheumatoid arthritis contributes to biology and drug discovery

A major challenge in human genetics is to devise a systematic strategy to integrate disease-associated variants with diverse genomic and biological datasets to provide insight into disease pathogenesis and guide drug discovery for complex traits such as rheumatoid arthritis (RA)1. Here, we performed a genome-wide association study (GWAS) meta-analysis in a total of >100,000 subjects of European and Asian ancestries (29,880 RA cases and 73,758 controls), by evaluating ~10 million single nucleotide polymorphisms (SNPs). We discovered 42 novel RA risk loci at a genome-wide level of significance, bringing the total to 1012–4. We devised an in-silico pipeline using established bioinformatics methods based on functional annotation5, cis-acting expression quantitative trait loci (cis-eQTL)6, and pathway analyses7–9 – as well as novel methods based on genetic overlap with human primary immunodeficiency (PID), hematological cancer somatic mutations and knock-out mouse phenotypes – to identify 98 biological candidate genes at these 101 risk loci. We demonstrate that these genes are the targets of approved therapies for RA, and further suggest that drugs approved for other indications may be repurposed for the treatment of RA. Together, this comprehensive genetic study sheds light on fundamental genes, pathways and cell types that contribute to RA pathogenesis, and provides empirical evidence that the genetics of RA can provide important information for drug discovery

Automatic versus manual pressure support reduction in the weaning of post-operative patients: a randomized controlled trial

INTRODUÇÃO: A redução automática da pressão de suporte (PS) baseada na freqüência respiratória, ou MRV (mandatory rate ventilation) é um modo ventilatório disponível no ventilador Taema-Horus. A hipótese do estudo é que o MRV utilizado no desmame é tão efetivo quanto o desmame manual em pacientes em pós-operatório na unidade de terapia intensiva (UTI). MÉTODOS: Ao chegar à UTI, após a cirurgia, os pacientes eram randomizados em dois grupos: desmame manual ou automático. O desmame manual consistiu na redução manual da PS a cada 30 minutos mantendo a relação freqüência respiratória sobre volume corrente menor do que 80, até a PS de 5-7 cmH2O. O desmame automático baseou-se na freqüência respiratória alvo de 15 respirações por minuto (o ventilador diminui automaticamente, a PS em 1 cmH2O a cada 4 ciclos respiratórios, se o paciente mantiver a freqüência respiratória abaixo deste valor). O objetivo primário do estudo foi comparar a duração do processo de desmame. Secundariamente verificamos o nível de PS, freqüência respiratória, volume corrente, índice de freqüência respiratória sobre volume corrente, pressão positiva expiratória final, fração inspirada de oxigênio e saturação de oxigênio requeridos durante o processo de desmame. Verificamos também necessidade de reintubação e necessidade de ventilação não invasiva nas primeiras 48 horas após a extubação. RESULTADOS: Não houve diferença estatística significativa entre os 53 pacientes selecionados em cada grupo quanto ao sexo (p=0541), idade (p=0,585) e tipo de cirurgia (p=0,172). Dezenove pacientes foram excluídos durante o protocolo (quatro no grupo manual e quinze no grupo automático, p<0,05). Nove pacientes do grupo automático foram excluídos do protocolo por não se adaptarem ao modo de desmame automático. Oitenta e sete pacientes concluíram o estudo, quarenta e nove pacientes foram desmamados manualmente e trinta e oito automaticamente. A duração do processo de desmame foi de 205,41±181,27 minutos (de 30 a 840 minutos) no grupo manual, e 157,33±129,98 minutos (de 30 a 545 minutos) no grupo automático. Não houve diferença estatística significante quanto ao tempo de desmame entre os dois grupos. O nível de PS foi maior (p<0,001) e freqüência respiratória foi menor (p=0,0098) no modo MRV comparado ao modo manual, durante o processo de desmame. Não houve necessidade de reintubação em nenhum dos grupos. Houve necessidade de ventilação não invasiva em dois pacientes do grupo manual (p=0,505), ambos sofreram cirurgia cardíaca. CONCLUSÃO: A redução automática da PS foi efetiva e pode ser utilizada no desmame de pacientes no pós-operatório na unidade de terapia intensiva, se o paciente se adaptar ao algoritmo do MRVIntroduction: Automatic pressure support reduction based on a target respiratory frequency or MRV is available in the TAEMA-HORUS ventilator for the weaning process in the ICU setting. We hypothesized that MRV is as effective as manual weaning in post-operative ICU patients. Methods: There were 106 patients selected, in the post-operative period in a prospective, randomized, controlled protocol. When the patients arrived in the ICU after surgery, they were randomly assigned to traditional weaning, consisted of the manual reduction of pressure support every thirty minutes, keeping the RR/TV(L) < 80 till 5-7 cmH20 of PSV. Alternatively, they were assigned to automatic weaning, referring to MRV set with a respiratory frequency target of 15 breaths per minute (the ventilator automatically decreased the PSV level by 1 cmH20 every 4 respiratory cycles, if the patients RR was less than 15 per minute). The primary endpoint of the study was the duration of the weaning process. Secondary endpoints were levels of pressure support, respiratory rate, tidal volume (mL), RR/VT (L), PEEP levels FiO2 and SpO2 required during the weaning process, the need for reintubation and the need for non-invasive ventilation in the 48 hours after extubation. Results: There were no statistically significant differences between the 53 patients selected for each group regarding gender (p=0.541), age (p=0.585) and type of surgery (p=0.172). Nineteen patients were excluded during the trial (4 in the PSV group and 15 in the MRV group, p<0.05). Eighty-seven patients concluded the study, forty-nine patients were weaned manually and thirtyeight automatically. The weaning duration process was 205.41 ± 181.27 minutes (30 to 840 minutes) for the manual group and 157. 33± 129.98 minutes (30 to 545 minutes) for MRV group (p=0.167). PSV levels were significantly higher and RR was lower in MRV compared to that of the PSV manual reduction (p<0.05). Reintubation was not required in either group. NIV was necessary for two patients, in the manual group after cardiac surgery (p=0.505). Conclusion: The automatic reduction of pressure support was effective and can be useful for weaning patients in the post-operative period in the ICU, if the patient is receptive to the MRV algorith