Spatial distribution of sequential ventilation during mechanical ventilation of the uninjured lung: an argument for cyclical airway collapse and expansion

<p>Abstract</p> <p>Background</p> <p>Ventilator-induced lung injury (VILI) is a recognized complication of mechanical ventilation. Although the specific mechanism by which mechanical ventilation causes lung injury remains an active area of study, the application of positive end expiratory pressure (PEEP) reduces its severity. We have previously reported that VILI is spatially heterogeneous with the most severe injury in the dorsal-caudal lung. This regional injury heterogeneity was abolished by the application of PEEP = 8 cm H₂O. We hypothesized that the spatial distribution of lung injury correlates with areas in which cyclical airway collapse and recruitment occurs.</p> <p>Methods</p> <p>To test this hypothesis, rabbits were mechanically ventilated in the supine posture, and regional ventilation distribution was measured under four conditions: tidal volumes (V_T) of 6 and 12 ml/kg with PEEP levels of 0 and 8 cm H₂O.</p> <p>Results</p> <p>We found that relative ventilation was sequentially redistributed towards dorsal-caudal lung with increasing tidal volume. This sequential ventilation redistribution was abolished with the addition of PEEP.</p> <p>Conclusions</p> <p>These results suggest that cyclical airway collapse and recruitment is regionally heterogeneous and spatially correlated with areas most susceptible to VILI.</p

Perineal rectosigmoidectomy for rectal prolapse:the preferred procedure for the unfit elderly patient? 10 years’ experience from a UK tertiary centre

Background: Rectal prolapse is a disease presentation with a prevalence of about 1%, mainly affecting older women. It usually presents with symptoms of rectal mass, rectal bleeding, fecal incontinence or constipation, with patients frequently feeling socially isolated as a result. Perineal rectosigmoidectomy is associated with lesser morbidity and mortality than the abdominal procedure, but with a much higher recurrence rate. Therefore, this technique is mainly suitable for the frail elderly patient. Specific outcomes in an elderly population have been described in only a few studies. We evaluated the morbidity, mortality, recurrence rate and functional results after this procedure related to age.Methods: All patients who underwent a perineal rectosigmoidectomy over a 10-year period in two tertiary referral centers were included in the study. American Society of Anesthesiology (ASA) grade, pre- and postoperative symptoms, pathology-reported post-fixation specimen length, length of in-patient stay, 30-day morbidity/mortality, and recurrence were measured.Results: A total of 45 patients underwent a perineal rectosigmoidectomy. Forty-three (95%) were female, with a median age of 82.0 years (IQR 70.5–86.5), ASA grade III and median follow-up of 20 months (range 8.5–45.5 months). Half of the cohort was over 80 years old. Significant symptomatic relief was achieved, predominantly the resolution of rectal mass (8.9% vs. 60.0% preoperatively), fecal incontinence (15.6% vs. 46.7%) and constipation (4.4% vs. 26.7%). The median length of stay was 6 days, while morbidity occurred in 14 patients (31.1%) and recurrence occurred in 6 patients (13%). There were no deaths within 30 days of the procedure and outcomes were comparable in the &lt; 80 and ≥ 80 age group.Conclusions: Perineal rectosigmoidectomy is safe for older patients with greater comorbidities resulting in good functional results and is associated with low morbidity and mortality.</p

Increased Expression of AQP 1 and AQP 5 in Rat Lungs Ventilated with Low Tidal Volume is Time Dependent

Background and GoalsMechanical ventilation (MV) can induce or worsen pulmonary oedema. Aquaporins (AQPs) facilitate the selective and rapid bi-directional movement of water. Their role in the development and resolution of pulmonary oedema is controversial. Our objectives are to determine if prolonged MV causes lung oedema and changes in the expression of AQP 1 and AQP 5 in rats.Methods25 male Wistar rats were subjected to MV with a tidal volume of 10 ml/kg, during 2 hours (n = 12) and 4 hours (n = 13). Degree of oedema was compared with a group of non-ventilated rats (n = 5). The expression of AQP 1 and AQP 5 were determined by western immunoblotting, measuring the amount of mRNA (previously amplified by RT-PCR) and immunohistochemical staining of AQPs 1 and 5 in lung samples from all groups.ResultsLung oedema and alveolar-capillary membrane permeability did not change during MV. AQP-5 steady state levels in the western blot were increased (p<0.01) at 2 h and 4 h of MV. But in AQP-1 expression these differences were not found. However, the amount of mRNA for AQP-1 was increased at 2 h and 4 h of MV; and for AQP 5 at 4 h of MV. These findings were corroborated by representative immunohistochemical lung samples.ConclusionIn lungs from rats ventilated with a low tidal volume the expression of AQP 5 increases gradually with MV duration, but does not cause pulmonary oedema or changes in lung permeability. AQPs may have a protective effect against the oedema induced by MV

Pyrrolidine dithiocarbamate administered during ex-vivo lung perfusion promotes rehabilitation of injured donor rat lungs obtained after prolonged warm ischemia.

Damaged lung grafts obtained after circulatory death (DCD lungs) and warm ischemia may be at high risk of reperfusion injury after transplantation. Such lungs could be pharmacologically reconditioned using ex-vivo lung perfusion (EVLP). Since acute inflammation related to the activation of nuclear factor kappaB (NF-κB) is instrumental in lung reperfusion injury, we hypothesized that DCD lungs might be treated during EVLP by pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-κB. Rat lungs exposed to 1h warm ischemia and 2 h cold ischemia were subjected to EVLP during 4h, in absence (CTRL group, N = 6) or in presence of PDTC (2.5g/L, PDTC group, N = 6). Static pulmonary compliance (SPC), peak airway pressure (PAWP), pulmonary vascular resistance (PVR), and oxygenation capacity were determined during EVLP. After EVLP, we measured the weight gain of the heart-lung block (edema), and the concentration of LDH (cell damage), proteins (permeability edema) and of the cytokines IL-6, TNF-α and CINC-1 in bronchoalveolar lavage (BAL), and we evaluated NF-κB activation by the degree of phosphorylation and degradation of its inhibitor IκBα in lung tissue. In CTRL, we found significant NF-κB activation, lung edema, and a massive release of LDH, proteins and cytokines. SPC significantly decreased, PAWP and PVR increased, while oxygenation tended to decrease. Treatment with PDTC during EVLP inhibited NF-κB activation, did not influence LDH release, but markedly reduced lung edema and protein concentration in BAL, suppressed TNFα and IL-6 release, and abrogated the changes in SPC, PAWP and PVR, with unchanged oxygenation. In conclusion, suppression of innate immune activation during EVLP using the NF-κB inhibitor PDTC promotes significant improvement of damaged rat DCD lungs. Future studies will determine if such rehabilitated lungs are suitable for in vivo transplantation

Executive function and IQ predict mathematical and attention problems in very preterm children

Objective of this study was to examine the impact of executive function (EF) on mathematical and attention problems in very preterm (gestational age ≤ 30 weeks) children. Participants were 200 very preterm (mean age 8.2 ± 2.5 years) and 230 term children (mean age 8.3 ± 2.3 years) without severe disabilities, born between 1996 and 2004. EFs assessed included verbal fluency, verbal working memory, visuospatial span, planning, and impulse control. Mathematics was assessed with the Dutch Pupil Monitoring System and parents and teachers rated attention problems using standardized behavior questionnaires. The impact of EF was calculated over and above processi

Comparison of the effect of lps and pam3 on ventilated lungs

<p>Abstract</p> <p>Background</p> <p>While lipopolysaccharide (LPS) from Gram-negative bacteria has been shown to augment inflammation in ventilated lungs information on the effect of Gram-positive bacteria is lacking. Therefore the effect of LPS and a lipopetide from Gram-positive bacteria, PAM3, on ventilated lungs were investigated.</p> <p>Methods</p> <p>C57/Bl6 mice were mechanically ventilated. Sterile saline (sham) and different concentrations of LPS (1 μg and 5 μg) and PAM3 (50 nM and 200 nM) were applied intratracheally. Lung function parameters and expression of MIP-2 and TNFα as well as influx of neutrophils were measured.</p> <p>Results</p> <p>Mechanical ventilation increased resistance and decreased compliance over time. PAM3 but not LPS significantly increased resistance compared to sham challenge (P < 0.05). Both LPS and PAM3 significantly increased MIP-2 and TNFα mRNA expression compared to sham challenge (P < 0.05). The numbers of neutrophils were significantly increased after LPS at a concentration of 5 μg compared to sham (P < 0.05). PAM3 significantly increased the numbers of neutrophils at both concentrations compared to sham (P < 0.05).</p> <p>Conclusions</p> <p>These data suggest that PAM3 similar to LPS enhances ventilator-induced inflammation. Moreover, PAM3 but not LPS increases pulmonary resistance in ventilated lungs. Further studies are warranted to define the role of lipopetides in ventilator-associated lung injury.</p

Enhanced chlorhexidine skin penetration with 1,8-cineole

BACKGROUND: Chlorhexidine (CHG) penetrates poorly into skin. The purpose of this study was to compare the depth of CHG skin permeation from solutions containing either 2% (w/v) CHG and 70% (v/v) isopropyl alcohol (IPA) or 2% (w/v) CHG, 70% (v/v) IPA and 2% (v/v) 1,8-cineole. METHODS: An ex-vivo study using Franz diffusion cells was carried out. Full thickness human skin was mounted onto the cells and a CHG solution, with or without 2% (v/v) 1,8-cineole was applied to the skin surface. After twenty-four hours the skin was sectioned horizontally in 100 μm slices to a depth of 2000 μm and the concentration of CHG in each section quantified using high performance liquid chromatography (HPLC). The data were analysed with repeated measures analysis of variance. RESULTS: The concentration of CHG in the skin on average was significantly higher (33.3% [95%, CI 1.5% - 74.9%]) when a CHG solution which contained 1,8-cineole was applied to the skin compared to a CHG solution which did not contain this terpene (P = 0.042). CONCLUSIONS: Enhanced delivery of CHG can be achieved in the presence of 1,8-cineole, which is the major component of eucalyptus oil. This may reduce the numbers of microorganisms located in the deeper layers of the skin which potentially could decrease the risk of surgical site infection

Uso de iodóforo tópico em feridas crônicas: revisão da literatura

La investigación trata de una revisión de la literatura a cerca de la utilización del yodo tópico y/o compuestos en el tratamiento de las heridas crónicas. Se buscaran los ensayos clínicos en el Cochrane. Catorce (n=24) publicaciones estaban de acuerdo con los criterios de inclusión, y fueran analizadas según las características de las revistas y ensayos y clasificadas como: yodo versus otros agentes tópicos (7/ 50%); yodo versus curativos (6/ 42,9%) y yodo versus sin yodo (1/ 7,1%). Fueran obtenidos resultados favorables a la utilización del yodo y/o compuestos en 50% de los artículos analizados. Cuanto a las tendencias de los resultados, 6 de 8 publicaciones, a cerca de la de cicatrización de las heridas y prevención de infección, fueran favorables; 4 de 5 fueran no favorables solamente para la cicatrización, y el resultado del único trabajo con indicación del uso para tratamiento de infección de herida fue no favorable.Trata-se de revisão de literatura relacionada ao uso de iodóforos tópicos no tratamento de feridas crônicas. Os ensaios clínicos foram localizados por meio da Base de Dados Cochrane de Revisões Sistemáticas e Registro Cochrane Central de Ensayos Controlados. Quatorze (58,3%), dentre 24 artigos, atenderam os critérios de inclusão, analisados quanto às características dos periódicos e dos estudos e classificados em três grupos: iodóforo versus outros agentes tópicos (7 ou 50%); iodóforo versus coberturas (6 ou 42,9%) e iodóforo versus sem iodóforo (1 ou 7,1%). Resultados favoráveis à utilização dos iodóforos ocorreram em 50% dos artigos analisados. Quanto às tendências dos resultados, seis, dentre oito artigos, que tratavam de cicatrização de feridas e prevenção de infecção, foram favoráveis; quatro, dentre cinco, foram desfavoráveis somente para a cicatrização e no único ensaio em que houve indicação do seu uso para tratamento de infecção de ferida o resultado foi desfavorável.This study aimed to do a review of the literature regarding the use of topic iodine and/or compounds in the treatment of chronic wounds. The clinical trials were searched in the Cochrane database. Fourteen (58.3%) among 24 studies fulfilled the inclusion criteria. The articles were analyzed regarding journal and study characteristics and classified into three groups: Iodine versus other topic agents (7/ 50%); Iodine versus different dressings (6/ 42.9%); Iodine versus without Iodine (1/ 7.1%). Favorable results for the use of Iodine or similar product occurred in 50% of the analyzed studies. Six out of 8 trials showed favorable results for healing and infection prevention/ treatment; 4 out of 5 were not favorable when the healing objective was investigated and 1 study for infection treatment showed no favorable result

Clinicians’ response to hyperoxia in ventilated patients in a Dutch ICU depends on the level of FiO2

Hyperoxia may induce pulmonary injury and may increase oxidative stress. In this retrospective database study we aimed to evaluate the response to hyperoxia by intensivists in a Dutch academic intensive care unit. All arterial blood gas (ABG) data from mechanically ventilated patients from 2005 until 2009 were extracted from an electronic storage database of a mixed 32-bed intensive care unit in a university hospital in Amsterdam. Mechanical ventilation settings at the time of the ABG tests were retrieved. The results of 126,778 ABG tests from 5,498 mechanically ventilated patients were retrieved including corresponding ventilator settings. In 28,222 (22%) of the ABG tests the arterial oxygen tension (PaO2) was > 16 kPa (120 mmHg). In only 25% of the tests with PaO2 > 16 kPa (120 mmHg) was the fraction of inspired oxygen (FiO(2)) decreased. Hyperoxia was accepted without adjustment in ventilator settings if FiO(2) was 0.4 or lower. Hyperoxia is frequently seen but in most cases does not lead to adjustment of ventilator settings if FiO(2) <0.41. Implementation of guidelines concerning oxygen therapy should be improved and further research is needed concerning the effects of frequently encountered hyperoxi