Acute renal response to changes in carbon dioxide in mechanically ventilated female pigs.

Kidney response to acute and mechanically induced variation in ventilation associated with different levels of PEEP has not been investigated. We aimed to quantify the effect of ventilatory settings on renal acid-base compensation. Forty-one pigs undergoing hypo- (<0.2 Lkg-1 min-1, PEEP 25 cmH2O), intermediate (0.2-0.4 Lkg-1 min-1 with either PEEP 5 or 25 cmH2O), or hyper-ventilation (>0.4 Lkg-1 min-1, PEEP 5 cmH2O) for 48 h were retrospectively included. The decrease in pH paralleled the decrease in plasma strong ion difference (SID) in hyper- and intermediately ventilated groups with lower PEEP. In contrast, the plasma SID remained nearly constant in hypo- and intermediately ventilated groups with higher PEEP. Changes in plasma chloride concentration accounted for the changes in plasma SID (conditional R2 = 0.86). The plasma SID changes were paralleled by mirror changes in urinary SID. Higher PEEP (25 cmH2O), compared to lower PEEP (5 cmH2O) dampened or abolished the renal compensation through its effect on hemodynamics (higher central venous and mean pulmonary pressures), irrespective of minute ventilation. During mechanical ventilation, the compensatory renal response to respiratory derangement is immediate and progressive but can be dampened by high PEEP levels.

Pulmonary ischaemia without pulmonary arterial thrombus in COVID-19 patients receiving extracorporeal membrane oxygenation: a cohort study.

AIM: To evaluate the incidence of pulmonary ischaemia in COVID-19 patients on extracorporeal membrane oxygenation (ECMO), and its correlation with pulmonary artery thrombosis. MATERIALS AND METHODS: Computed tomography (CT) thorax of all patients receiving ECMO with proven COVID-19 pneumonitis between March and May 2020 were analysed for the presence and extension of pulmonary thromboembolic disease. RESULTS: Fifty-one patients were reviewed. The mean (range) age of 45 (26-66) years; 38/51 (74.5%) were men. All patients had severe COVID-19 pneumonitis, and 18/51 (35.3%) had macroscopic thrombosis (15 with associated ischaemia); however, 13/51 (25.5%) patients had ischaemia without associated thrombus. CONCLUSION: The majority of patients with COVID-19 who received ECMO had areas of ischaemia within consolidated lungs, almost half of these without subtending pulmonary artery thrombosis. Although the prognostic significance of these findings is unclear, they are highly suggestive of lung ischaemia due to isolated microvascular immune thrombosis.

Diagnosis of death using neurological criteria in adult patients on extracorporeal membrane oxygenation: Development of UK guidance.

The diagnosis of death using neurological criteria is an important legal method of establishing death in the UK. The safety of the diagnosis lies in the exclusion of conditions which may mask the diagnosis and the testing of the fundamental reflexes of the brainstem including the apnoea reflex. Extracorporeal membrane oxygenation for cardiac or respiratory support can impact upon these tests, both through drug sequestration in the circuit and also through the ability to undertake the apnoea test. Until recently, there has been no nationally accepted guidance regarding the conduct of the tests to undertake the diagnosis of death using neurological criteria for a patient on extracorporeal membrane oxygenation. This article considers both the background to and the process of guideline development.

Acute kidney injury as a risk factor of hyperactive delirium: A case control study.

PURPOSE: Delirium and acute kidney injury (AKI) are common organ dysfunctions during critical illness. Both conditions are associated with serious short- and long-term complications. We investigated whether AKI is a risk factor for hyperactive delirium. METHODS: This was a single-centre case control study conducted in a 30 bedded mixed Intensive Care Unit in the UK. Hyperactive delirium cases were identified by antipsychotic initiation and confirmation of delirium diagnosis through validated chart review. Cases were compared with non-delirium controls matched by Acute Physiology and Chronic Health Evaluation II score and gender. AKI was defined by the KDIGO criteria. RESULTS: 142 cases and 142 matched controls were identified. AKI stage 3 was independently associated with hyperactive delirium [Odds ratio (OR) 5.40 (95% confidence interval (CI) 2.33-12.51]. Other independent risk factors were mechanical ventilation [OR 2.70 (95% CI 1.40-5.21)], alcohol use disorder [OR 5.80 (95% CI 1.90-17.72)], and dementia [OR 9.76 (95% CI 1.09-87.56)]. Hospital length of stay was significantly longer in delirium cases (29 versus 20 days; p = .004) but hospital mortality was not different. CONCLUSIONS: AKI stage 3 is independently associated with hyperactive delirium. Further research is required to explore the factors that contribute to this association.

Assessment of Work of Breathing in Patients with Acute Exacerbations of Chronic Obstructive Pulmonary Disease.

The assessment of the work of breathing (WOB) of patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) is difficult, particularly when the patient first presents with acute hypercapnia and respiratory acidosis. Acute exacerbations of COPD patients are in significant respiratory distress and noninvasive measurements of WOB are easier for the patient to tolerate. Given the interest in using alternative therapies to noninvasive ventilation, such as high flow nasal oxygen therapy or extracorporeal carbon dioxide removal, understanding the physiological changes are key and this includes assessment of WOB. This narrative review considers the role of three different methods of assessing WOB in patients with acute exacerbations of COPD. Esophageal pressure is a very well validated measure of WOB, however the ability of patients with acute exacerbations of COPD to tolerate esophageal tubes is poor. Noninvasive alternative measurements include parasternal electromyography (EMG) and electrical impedance tomography (EIT). EMG is easily applied and is a well validated measure of neural drive but is more likely to be degraded by the electrical environment in intensive care or high dependency. EIT is less well validated as a tool for WOB in COPD but extremely well tolerated by patients. Each of the different methods assess WOB in a different way and have different advantages and disadvantages. For research into therapies treating acute exacerbations of COPD, combinations of EIT, EMG and esophageal pressure are likely to be better than only one of these.

Outcomes of emergency laparotomy in patients on extracorporeal membrane oxygenation for severe respiratory failure: A retrospective, observational cohort study.

PURPOSE: There is a paucity of literature to support undertaking emergency laparotomy when indicated in patients supported on ECMO. Our study aims to identify the prevalence, outcomes and complications of this high risk surgery at a large ECMO centre. MATERIALS AND METHODS: A single centre, retrospective, observational cohort study of 355 patients admitted to a university teaching hospital Severe Respiratory Failure service between December 2011 and January 2017. RESULTS: The prevalence of emergency laparotomy in patients on ECMO was 3.7%. These patients had significantly higher SOFA and APACHE II scores compared to similar patients not requiring laparotomy. There was no difference in the duration of ECMO or intensive care unit (ICU) stay post decannulation between the two groups. 31% of laparotomy patients survived to hospital discharge. Major haemorrhage was uncommon, however emergency change of ECMO oxygenator was commonly required. CONCLUSION: Survival to hospital discharge is possible following emergency laparotomy on ECMO, however the mortality is higher than for those patients not requiring laparotomy, this likely reflects the severity of underlying organ failure rather than the surgery itself. Our service's collocation with a general surgical service has made this development in care possible. ECMO service planning should consider general surgical provision.

Acceptance and transfer to a regional severe respiratory failure and veno-venous extracorporeal membrane oxygenation (ECMO) service: predictors and outcomes.

The use of extracorporeal membrane oxygenation for respiratory failure is high risk and resource intensive. In England, five centres provide this service and patients who are referred have four possible outcomes: declined transfer due to perceived futility; accepted in principle but remain at the referring centre with ongoing surveillance; retrieved using conventional ventilation; or retrieved on extracorporeal support. The decision-making process leading to these outcomes has not previously been examined. We evaluated referrals to one centre and identified factors associated with each decision outcome. Five hundred and sixty-four patients were analysed from January 2012 to October 2015. One hundred and fifty-seven patients were declined; multivariate analysis demonstrated associated factors to be: age (odds ratio (95% confidence interval) 1.05 (1.04-1.07)); immunocompromise (4.95 (2.58-9.67)); lactate (1.11 (1.01-1.22)); duration of ventilation (1.08 (1.04-1.14)); and cardiac failure (3.22 (1.04-10.51)). Factors associated with the decision to retrieve an accepted patient were: plateau pressure (1.05 (1.01-1.10)); ratio of arterial oxygen partial pressure to fractional inspired oxygen (0.89 (0.85-0.93)); partial pressure of carbon dioxide in arterial blood (1.13 (1.03-1.25)); and the absence of non-pulmonary infection (0.31 (0.15-0.61)). Only pH was independently associated with the decision to transfer on extracorporeal support (0.020 (0.002-0.017)). Six-month survival in the declined, non-retrieved, conventionally retrieved and extracorporeal-retrieved groups was 16.6%, 71.1%, 76.7% and 72.1%, respectively, substantially supporting the decision-making model. Survival in the accepted group exceeds that reported previously. However, a proportion of those declined do survive and some remotely managed patients die. This suggests the approach does not account for some important survival-determining factors.

International survey on the management of mechanical ventilation during ECMO in adults with severe respiratory failure.

BACKGROUND: No consensus exists on the optimal settings of mechanical ventilation during veno-venous extracorporeal membrane oxygenation (ECMO). Our aim was to describe how mechanical ventilation and related interventions are managed by adult ECMO centres. METHODS: A cross-sectional, multi-centre, international survey of 173 adult respiratory ECMO centres. The survey was generated through an iterative process and assessed for clarity, content and face validity. RESULTS: One hundred thirty-three centres responded (76.8%). Pressure control was the most commonly used mechanical ventilation mode (64.4%). Although the median PEEP was 10 cmH2O, 22.6% set PEEP <10 cmH2O and 15.5% used 15-20 cmH2O. In 63% of centres PEEP was fixed and not titrated. Recruitment maneuvres, were never used in 34.1% of centres, or used daily in 13.2%. Centres reported using either a "lung rest" (45.7%), or an "open lung" strategy (44.2%). Only 24.8% used chest CT to guide mechanical ventilation. Adjunctive treatments were never or occasionally used. Only 10% of centres extubated patients on ECMO, mainly in more experienced centres. 71.3% of centres performed tracheostomy on ECMO, with large variability in timing (most frequent on days 6-10). Only 27.1% of ECMO centres had a protocol for mechanical ventilation on ECMO. CONCLUSION: We found large variability in ventilatory practices during ECMO. The clinicians' training background and the centres' experience had no influence on the approach to ventilation. This survey shows that well conducted studies are necessary to determine the best practice of mechanical ventilation during ECMO and its impact on patient outcome.

What's new in the "Berlin" definition of acute respiratory distress syndrome?

A valid operative definition for ARDS is essential for the appropriate institution of a standardized 'best-evidence' treatment and for the identification of subgroups of patients who may benefit from specific adjunctive interventions, as well as to assist with prognostication, resource allocation and the design of new research trials. Here, we will discuss some of the methodology used by the ARDS Definition Task Force to develop the new 'Berlin' definition of ARDS, briefly discussing the rationale for the divergence from the AECC definition. The Berlin definition improves on the predictive validity for mortality of the American-European Consensus Conference's (AECC) definition and clarifies both the conceptual model of ARDS and the definition criteria of the syndrome and of its spectrum of severity. This should facilitate case recognition and more consistent treatment strategies based on severity.

The effects of Mycobacterium vaccae on allergen-induced airway responses in atopic asthma.

T-helper (Th)2 cytokines play a central role in asthma. Therefore, a double-blind randomised study was conducted to investigate whether heat-killed Mycobacterium vaccae (SRL172), a potent downregulator of Th2 cytokines, can reduce allergen-induced airway responses in patients with atopic asthma. A total 24 male asthmatics participated in this study. A bronchial allergen challenge was performed along with early (EAR) and late asthmatic responses (LAR) 2 weeks before and 3 weeks after a single intradermal injection of SRL172 or placebo. Before and after treatment, serum immunoglobulin (Ig)E levels and in vitro production of interleukin (IL)-5 by peripheral blood lymphocytes were studied. Neither treatment affected the EAR. SRL172 caused a mean 34% reduction of the area under the curve of the forced expiratory volume in one second (FEV1) changes during the LAR, which failed to reach conventional statistical significance when compared with placebo. SRL172 also caused a mean 25% decrease in the maximum fall in FEV1 during LAR, but this was not significantly different from placebo. SRL172 caused a reduction in serum IgE and IL-5 synthesis in vitro 3 weeks post-treatment (p = 0.07). This study shows a trend toward significance for the effects of heat-killed Mycobacterium vaccae (SRL172) on allergen-induced airway responses. Further clinical trials, involving multiple dosing, are needed.

Effects of specific immunotherapy in allergic rhinitic individuals with bronchial hyperresponsiveness.

Allergic rhinitis can be associated with bronchial hyperresponsiveness (BHR), and carries an increased risk for the development of asthma. The aim of this study was to evaluate the ability of specific immunotherapy (SIT) to reduce the progression of allergic rhinitis to asthma and prevent the associated increase in BHR. Forty-four subjects monosensitized to Dermatophagoides pteronyssinus, with perennial rhinitis and BHR to methacholine, were randomly assigned to receive SIT or placebo in a double-blind study conducted over a period of 2 yr. After 1 yr of treatment, a 2.88-fold increase in the provocative dose of methacholine producing a 20% decrease in FEV(1) (PD(20)FEV(1)) was recorded in the SIT-treated group (95% confidence interval [CI]: 3.98- to 2.09-fold; p < 0.001), with a further increase to fourfold at the end of Year 2 (95% CI: 2.9- to 5.7-fold; p < 0.001). At the end of the study, the methacholine PD(20)FEV(1) was within the normal range in 50% of treated subjects (p < 0.0001), and was significantly higher in this group than in the group receiving placebo (p < 0.0001). In contrast, no changes in methacholine PD(20)FEV(1) were found in the placebo group throughout the study. Although 9% of subjects given placebo developed asthma, none of those treated with SIT did. This study suggests that SIT, when administered to carefully selected, monosensitized patients with perennial allergic rhinitis, reduces airway responsiveness in subjects with rhinitis, and may be an appropriate prophylactic treatment for rhinitic patients with hyperreactive airways.