Does Tracheostomy Improve Outcomes in Those Receiving Venovenous Extracorporeal Membrane Oxygenation?

Patients receiving venovenous extracorporeal membrane oxygenation (VV-ECMO) often require extended periods of ventilation. We examined the role of tracheostomy on outcomes of patients supported with VV-ECMO. We reviewed all patients at our institution who received VV-ECMO between 2013 and 2019. Patients who received a tracheostomy were compared with VV-ECMO-supported patients without tracheostomy. The primary outcome measure was survival to hospital discharge. Secondary outcome measures included length of intensive care unit (ICU) and hospital stay and adverse events related to the tracheostomy procedure. Multivariable analysis was performed to identify predictors of in-hospital mortality. We dichotomized patients receiving tracheostomy into an "early" and "late" group based on median days to tracheostomy following ECMO cannulation and separate analysis was performed. One hundred and fifty patients met inclusion criteria, 32 received a tracheostomy. Survival to discharge was comparable between the groups (53.1% vs. 57.5%, p = 0.658). Predictors of mortality on multivariable analysis included Respiratory ECMO Survival Prediction (RESP) score (odds ratio [OR] = 0.831, p = .015) and blood urea nitrogen (BUN) (OR = 1.026, p = 0.011). Tracheostomy performance was not predictive of mortality (OR = 0.837, p = 0.658). Bleeding requiring intervention occurred in 18.7% of patients following tracheostomy. Early tracheostomy (<7 days from the initiation of VV-ECMO) was associated with shorter ICU (25 vs. 36 days, p = 0.04) and hospital (33 vs. 47, p = 0.017) length of stay compared with late tracheostomy. We conclude that tracheostomy can be performed safely in patients receiving VV-ECMO. Mortality in these patients is predicted by severity of the underlying disease. Performance of tracheostomy does not impact survival. Early tracheostomy may decrease length of stay.

Basics of Extracorporeal Membrane Oxygenation.

OVERVIEW: The use of extracorporeal membrane oxygenation (ECMO) is becoming commonplace worldwide in ICUs for the care of patients with respiratory and/or cardiac failure. Understanding the use of ECMO and the management of these complex patients will be vital to current and future clinicians as ECMO use continues to grow.

The effect of vasoactive agents on post-pressure hyperemia.

The cutaneous hyperemic response following the release of direct pressure occlusion lasts much longer than the short-term hyperemia that occurs after proximal arterial occlusion. Post-pressure hyperemia may be an important mechanism to prevent pressure induced injury to the skin. The role of vasoactive mediators in modulating post-pressure hyperemia is unknown. In an effort to better understand this phenomenon, we performed an initial study using microdialysis infusion to measure the effect of several known mediators of vascular response on post-pressure hyperemia. A vise clamp was used to apply direct occlusive pressure to a laser Doppler sensor on the skin surface overlying the microdialysis fiber. Skin blood flow was measured continuously pre, during and post-occlusion while infusing the vasoactive substance or control phosphate buffer. Angiotensin II, Calcitonin gene related peptide and histamine had minimal effect on post pressure blood flow. Conversely, prostaglandin E1, prostaglandin E2, and L-NAME diminished the early phase of the post-occlusion hyperemic response. Perhaps the most profound effect we observed was the decrease in post-occlusive blood flow due to administration of epinephrine, dopamine and prostaglandin F2alpha. In contrast, adenosine and caffeine augmented blood flow post occlusion. In this initial survey study, we have demonstrated differential effects of various vascular mediators on the post-pressure hyperemic phenomenon. Our findings may lead to the development of agents to prevent pressure sores by augmenting the skin blood flow response to locally applied pressure.

Single nucleotide polymorphisms (SNPs) distinguish Indian-origin and Chinese-origin rhesus macaques (Macaca mulatta).

BACKGROUND: Rhesus macaques serve a critical role in the study of human biomedical research. While both Indian and Chinese rhesus macaques are commonly used, genetic differences between these two subspecies affect aspects of their behavior and physiology, including response to simian immunodeficiency virus (SIV) infection. Single nucleotide polymorphisms (SNPs) can play an important role in both establishing ancestry and in identifying genes involved in complex diseases. We sequenced the 3' end of rhesus macaque genes in an effort to identify gene-based SNPs that could distinguish between Indian and Chinese rhesus macaques and aid in association analysis. RESULTS: We surveyed the 3' end of 94 genes in 20 rhesus macaque animals. The study included 10 animals each of Indian and Chinese ancestry. We identified a total of 661 SNPs, 457 of which appeared exclusively in one or the other population. Seventy-nine additional animals were genotyped at 44 of the population-exclusive SNPs. Of those, 38 SNPs were confirmed as being population-specific. CONCLUSION: This study demonstrates that the 3' end of genes is rich in sequence polymorphisms and is suitable for the efficient discovery of gene-linked SNPs. In addition, the results show that the genomic sequences of Indian and Chinese rhesus macaque are remarkably divergent, and include numerous population-specific SNPs. These ancestral SNPs could be used for the rapid scanning of rhesus macaques, both to establish animal ancestry and to identify gene alleles that may contribute to the phenotypic differences observed in these populations.

Leveraging human genomic information to identify nonhuman primate sequences for expression array development.

BACKGROUND: Nonhuman primates (NHPs) are essential for biomedical research due to their similarities to humans. The utility of NHPs will be greatly increased by the application of genomics-based approaches such as gene expression profiling. Sequence information from the 3' end of genes is the key resource needed to create oligonucleotide expression arrays. RESULTS: We have developed the algorithms and procedures necessary to quickly acquire sequence information from the 3' end of nonhuman primate orthologs of human genes. To accomplish this, we identified terminal exons of over 15,000 human genes by aligning mRNA sequences with genomic sequence. We found the mean length of complete last exons to be approximately 1,400 bp, significantly longer than previous estimates. We designed primers to amplify genomic DNA, which included at least 300 bp of the terminal exon. We cloned and sequenced the PCR products representing over 5,500 Macaca mulatta (rhesus monkey) orthologs of human genes. This sequence information has been used to select probes for rhesus gene expression profiling. We have also tested 10 sets of primers with genomic DNA from Macaca fascicularis (Cynomolgus monkey), Papio hamadryas (Baboon), and Chlorocebus aethiops (African green monkey, vervet). The results indicate that the primers developed for this study will be useful for acquiring sequence from the 3' end of genes for other nonhuman primate species. CONCLUSION: This study demonstrates that human genomic DNA sequence can be leveraged to obtain sequence from the 3' end of NHP orthologs and that this sequence can then be used to generate NHP oligonucleotide microarrays. Affymetrix and Agilent used sequences obtained with this approach in the design of their rhesus macaque oligonucleotide microarrays.