Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Guideline on the peri-operative management of patients with sickle cell disease: Guideline from the Association of Anaesthetists

Sickle cell disease is a multisystem disease characterised by chronic haemolytic anaemia, painful vaso-occlusive crises and acute and chronic end-organ damage. It is one of the most common serious inherited single gene conditions worldwide and has a major impact on the health of affected individuals. Peri-operative complications are higher in patients with sickle cell disease compared with the general population and may be sickle or non-sickle-related. Complications may be reduced by meticulous peri-operative care and transfusion, but unnecessary transfusion should be avoided, particularly to reduce the risk of allo-immunisation. Planned surgery and anaesthesia for patients with sickle cell disease should ideally be undertaken in centres with experience in caring for these patients. In an emergency, advice should be sought from specialists with experience in sickle cell disease through the haemoglobinopathy network arrangements. Emerging data suggest that patients with sickle cell disease are at increased risk of COVID-19 infection but may have a relatively mild clinical course. Outcomes are determined by pre-existing comorbidities, as for the general population

COVID-19: UK frontline intensivists' emerging learning

The Intensive Care Society held a webinar on 3 April 2020 at which representatives from 11 of the most COVID-19 experienced hospital trusts in England and Wales shared learning around five specific topic areas in an open forum. This paper summarises the emerging learning and practice shared by those frontline clinicians

Sublingual microcirculatory blood flow and vessel density in Sherpas at high altitude

Anecdotal reports suggest that Sherpa highlanders demonstrate extraordinary tolerance to hypoxia at high altitude despite exhibiting a lower arterial oxygen content than acclimatised Lowlanders. This study tested the hypothesis that Sherpas exposed to hypobaric hypoxia on ascent to 5300m, develop increased microcirculatory blood flow as a means of maintaining normal tissue oxygen delivery. Images of the sublingual microcirculation were obtained from 64 Sherpas and 69 Lowlanders using incident dark field imaging. Serial measurements were obtained from participants undertaking an ascent from baseline testing (35m or 1300m) to Everest base camp (5300m), and following subsequent descent in Kathmandu (1300m). Microcirculatory flow index and heterogeneity index were used to provide indices of microcirculatory flow, whilst capillary density was assessed using small vessel density. Sherpas, when compared to Lowlanders, demonstrated significantly greater microcirculatory blood flow at Everest Base Camp, but not at baseline testing or on return in Kathmandu. Additionally, Sherpa blood flow exhibited greater homogeneity at 5300m and 1300m (descent) when compared to Lowlanders. Sublingual small vessel density was not different between the two cohorts at baseline testing or at 1300m, however at 5300m Sherpas capillary density was up to 30% greater. These data suggest that Sherpas have the ability to maintain a significantly greater microcirculatory flow per unit time, and flow per unit volume of tissue at high altitude, when compared to Lowlanders. These findings support the notion that peripheral vascular factors at the microcirculatory level may be important in the process of adaptation to hypoxia

Physiological responses during ascent to high altitude and the incidence of acute mountain sickness.

Acute mountain sickness (AMS) occurs when there is failure of acclimatisation to high altitude. The aim of this study was to describe the relationship between physiological variables and the incidence of AMS during ascent to 5300 m. A total of 332 lowland-dwelling volunteers followed an identical ascent profile on staggered treks. Self-reported symptoms of AMS were recorded daily using the Lake Louise score (mild 3-4; moderate-severe ≥5), alongside measurements of physiological variables (heart rate, respiratory rate (RR), peripheral oxygen saturation (SpO2 ) and blood pressure) before and after a standardised Xtreme Everest Step-Test (XEST). The overall occurrence of AMS among participants was 73.5% (23.2% mild, 50.3% moderate-severe). There was no difference in gender, age, previous AMS, weight or body mass index between participants who developed AMS and those who did not. Participants who had not previously ascended >5000 m were more likely to get moderate-to-severe AMS. Participants who suffered moderate-to-severe AMS had a lower resting SpO2 at 3500 m (88.5 vs. 89.6%, p = 0.02), while participants who suffered mild or moderate-to-severe AMS had a lower end-exercise SpO2 at 3500 m (82.2 vs. 83.8%, p = 0.027; 81.5 vs. 83.8%, p 5000 m (OR 2.740, p-value 0.003) predicted the development of moderate-to-severe AMS. The Xtreme Everest Step-Test offers a simple, reproducible field test to help predict AMS, albeit with relatively limited predictive precision

Early onset torsion dystonia (Oppenheim's dystonia)

Early onset torsion dystonia (EOTD) is a rare movement disorder characterized by involuntary, repetitive, sustained muscle contractions or postures involving one or more sites of the body. A US study estimated the prevalence at approximately 1 in 30,000. The estimated prevalence in the general population of Europe seems to be lower, ranging from 1 in 330,000 to 1 in 200,000, although precise numbers are currently not available. The estimated prevalence in the Ashkenazi Jewish population is approximately five to ten times higher, due to a founder mutation. Symptoms of EOTD typically develop first in an arm or leg in middle to late childhood and progress in approximately 30% of patients to other body regions (generalized dystonia) within about five years. Distribution and severity of symptoms vary widely between affected individuals. The majority of cases from various ethnic groups are caused by an autosomal dominantly inherited deletion of 3 bp (GAG) in the DYT1 gene on chromosome 9q34. This gene encodes a protein named torsinA, which is presumed to act as a chaperone protein associated with the endoplasmic reticulum and the nuclear envelope. It may interact with the dopamine transporter and participate in intracellular trafficking, although its precise function within the cell remains to be determined. Molecular genetic diagnostic and genetic counseling is recommended for individuals with age of onset below 26 years, and may also be considered in those with onset after 26 years having a relative with typical early onset dystonia. Treatment options include botulinum toxin injections for focal symptoms, pharmacological therapy such as anticholinergics (most commonly trihexiphenydil) for generalized dystonia and surgical approaches such as deep brain stimulation of the internal globus pallidus or intrathecal baclofen application in severe cases. All patients have normal cognitive function, and despite a high rate of generalization of dystonia, 75% of those patients are able to maintain ambulation and independence, and therefore a comparatively good quality of life, with modern treatment modalities

Geoeconomic variations in epidemiology, ventilation management, and outcomes in invasively ventilated intensive care unit patients without acute respiratory distress syndrome: a pooled analysis of four observational studies

Background: Geoeconomic variations in epidemiology, the practice of ventilation, and outcome in invasively ventilated intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) remain unexplored. In this analysis we aim to address these gaps using individual patient data of four large observational studies. Methods: In this pooled analysis we harmonised individual patient data from the ERICC, LUNG SAFE, PRoVENT, and PRoVENT-iMiC prospective observational studies, which were conducted from June, 2011, to December, 2018, in 534 ICUs in 54 countries. We used the 2016 World Bank classification to define two geoeconomic regions: middle-income countries (MICs) and high-income countries (HICs). ARDS was defined according to the Berlin criteria. Descriptive statistics were used to compare patients in MICs versus HICs. The primary outcome was the use of low tidal volume ventilation (LTVV) for the first 3 days of mechanical ventilation. Secondary outcomes were key ventilation parameters (tidal volume size, positive end-expiratory pressure, fraction of inspired oxygen, peak pressure, plateau pressure, driving pressure, and respiratory rate), patient characteristics, the risk for and actual development of acute respiratory distress syndrome after the first day of ventilation, duration of ventilation, ICU length of stay, and ICU mortality. Findings: Of the 7608 patients included in the original studies, this analysis included 3852 patients without ARDS, of whom 2345 were from MICs and 1507 were from HICs. Patients in MICs were younger, shorter and with a slightly lower body-mass index, more often had diabetes and active cancer, but less often chronic obstructive pulmonary disease and heart failure than patients from HICs. Sequential organ failure assessment scores were similar in MICs and HICs. Use of LTVV in MICs and HICs was comparable (42\ub74% vs 44\ub72%; absolute difference \u20131\ub769 [\u20139\ub758 to 6\ub711] p=0\ub767; data available in 3174 [82%] of 3852 patients). The median applied positive end expiratory pressure was lower in MICs than in HICs (5 [IQR 5\u20138] vs 6 [5\u20138] cm H2O; p=0\ub70011). ICU mortality was higher in MICs than in HICs (30\ub75% vs 19\ub79%; p=0\ub70004; adjusted effect 16\ub741% [95% CI 9\ub752\u201323\ub752]; p<0\ub70001) and was inversely associated with gross domestic product (adjusted odds ratio for a US$10 000 increase per capita 0\ub780 [95% CI 0\ub775\u20130\ub786]; p<0\ub70001). Interpretation: Despite similar disease severity and ventilation management, ICU mortality in patients without ARDS is higher in MICs than in HICs, with a strong association with country-level economic status. Funding: No funding

Metabolic basis to Sherpa altitude adaptation.

The Himalayan Sherpas, a human population of Tibetan descent, are highly adapted to life in the hypobaric hypoxia of high altitude. Mechanisms involving enhanced tissue oxygen delivery in comparison to Lowlander populations have been postulated to play a role in such adaptation. Whether differences in tissue oxygen utilization (i.e., metabolic adaptation) underpin this adaptation is not known, however. We sought to address this issue, applying parallel molecular, biochemical, physiological, and genetic approaches to the study of Sherpas and native Lowlanders, studied before and during exposure to hypobaric hypoxia on a gradual ascent to Mount Everest Base Camp (5,300 m). Compared with Lowlanders, Sherpas demonstrated a lower capacity for fatty acid oxidation in skeletal muscle biopsies, along with enhanced efficiency of oxygen utilization, improved muscle energetics, and protection against oxidative stress. This adaptation appeared to be related, in part, to a putatively advantageous allele for the peroxisome proliferator-activated receptor A (PPARA) gene, which was enriched in the Sherpas compared with the Lowlanders. Our findings suggest that metabolic adaptations underpin human evolution to life at high altitude, and could have an impact upon our understanding of human diseases in which hypoxia is a feature.The work was supported by PhD studentships from the BBSRC to JH (BB/F016581/1) and British Heart Foundation to AK (FS/09/050), an Academic Fellowship to AM from the Research Councils UK (EP/E500552/1), a Physiological Society grant and support from Oroboros Instruments. JG thanks the MRC (MC UP A90 1006) and AB Sciex. MF thanks the MRC and Faculty of Medicine, Southampton University. For full acknowledgements see SI

Spontaneous Breathing in Early Acute Respiratory Distress Syndrome: Insights From the Large Observational Study to UNderstand the Global Impact of Severe Acute Respiratory FailurE Study

OBJECTIVES: To describe the characteristics and outcomes of patients with acute respiratory distress syndrome with or without spontaneous breathing and to investigate whether the effects of spontaneous breathing on outcome depend on acute respiratory distress syndrome severity. DESIGN: Planned secondary analysis of a prospective, observational, multicentre cohort study. SETTING: International sample of 459 ICUs from 50 countries. PATIENTS: Patients with acute respiratory distress syndrome and at least 2 days of invasive mechanical ventilation and available data for the mode of mechanical ventilation and respiratory rate for the 2 first days. INTERVENTIONS: Analysis of patients with and without spontaneous breathing, defined by the mode of mechanical ventilation and by actual respiratory rate compared with set respiratory rate during the first 48 hours of mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: Spontaneous breathing was present in 67% of patients with mild acute respiratory distress syndrome, 58% of patients with moderate acute respiratory distress syndrome, and 46% of patients with severe acute respiratory distress syndrome. Patients with spontaneous breathing were older and had lower acute respiratory distress syndrome severity, Sequential Organ Failure Assessment scores, ICU and hospital mortality, and were less likely to be diagnosed with acute respiratory distress syndrome by clinicians. In adjusted analysis, spontaneous breathing during the first 2 days was not associated with an effect on ICU or hospital mortality (33% vs 37%; odds ratio, 1.18 [0.92-1.51]; p = 0.19 and 37% vs 41%; odds ratio, 1.18 [0.93-1.50]; p = 0.196, respectively ). Spontaneous breathing was associated with increased ventilator-free days (13 [0-22] vs 8 [0-20]; p = 0.014) and shorter duration of ICU stay (11 [6-20] vs 12 [7-22]; p = 0.04). CONCLUSIONS: Spontaneous breathing is common in patients with acute respiratory distress syndrome during the first 48 hours of mechanical ventilation. Spontaneous breathing is not associated with worse outcomes and may hasten liberation from the ventilator and from ICU. Although these results support the use of spontaneous breathing in patients with acute respiratory distress syndrome independent of acute respiratory distress syndrome severity, the use of controlled ventilation indicates a bias toward use in patients with higher disease severity. In addition, because the lack of reliable data on inspiratory effort in our study, prospective studies incorporating the magnitude of inspiratory effort and adjusting for all potential severity confounders are required

Epidemiology and patterns of tracheostomy practice in patients with acute respiratory distress syndrome in ICUs across 50 countries

Background: To better understand the epidemiology and patterns of tracheostomy practice for patients with acute respiratory distress syndrome (ARDS), we investigated the current usage of tracheostomy in patients with ARDS recruited into the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG-SAFE) study. Methods: This is a secondary analysis of LUNG-SAFE, an international, multicenter, prospective cohort study of patients receiving invasive or noninvasive ventilation in 50 countries spanning 5 continents. The study was carried out over 4 weeks consecutively in the winter of 2014, and 459 ICUs participated. We evaluated the clinical characteristics, management and outcomes of patients that received tracheostomy, in the cohort of patients that developed ARDS on day 1-2 of acute hypoxemic respiratory failure, and in a subsequent propensity-matched cohort. Results: Of the 2377 patients with ARDS that fulfilled the inclusion criteria, 309 (13.0%) underwent tracheostomy during their ICU stay. Patients from high-income European countries (n = 198/1263) more frequently underwent tracheostomy compared to patients from non-European high-income countries (n = 63/649) or patients from middle-income countries (n = 48/465). Only 86/309 (27.8%) underwent tracheostomy on or before day 7, while the median timing of tracheostomy was 14 (Q1-Q3, 7-21) days after onset of ARDS. In the subsample matched by propensity score, ICU and hospital stay were longer in patients with tracheostomy. While patients with tracheostomy had the highest survival probability, there was no difference in 60-day or 90-day mortality in either the patient subgroup that survived for at least 5 days in ICU, or in the propensity-matched subsample. Conclusions: Most patients that receive tracheostomy do so after the first week of critical illness. Tracheostomy may prolong patient survival but does not reduce 60-day or 90-day mortality. Trial registration: ClinicalTrials.gov, NCT02010073. Registered on 12 December 2013