Search

In 2021 NHS England commissioned regional Adult Critical Care Transfer Services. These services will replace a historically predominant ad hoc approach to adult critical care transfers nationally. It is anticipated that these new formal services will provide a system of robust regional & national governance previously acknowledged to be deficient. As part of this process, it is important that an agreed set of transfer service quality indicators are developed to drive equitable improvement in patient care. We used a Delphi technique to develop a set of key performance indicators through consensus for a recently established London critical care transfer service. We believe this may be the first-time key performance indicators have been developed for adult critical care transfer services using a consensus method. We hope services will consider tracking similar measures to enable benchmarking and drive improvements in patient care.

In 2013, a group of clinicians on behalf of the National Institute for Health Research, collaborated with ICU Steps to produce guidance about people being enrolled in more than one critical care trial. This is referred to as “co-enrolment” and can be where a person takes part in one study at the same time as another study (or one after the other in a short time-frame). For instance, being part of a study looking at sepsis drugs and a mechanical ventilation weaning study. The drivers for developing this guidance were a lack of any existing guidance, nationally and internationally, at that time, and a desire to ensure high quality research is conducted. The emphasis was on making trials as safe as possible for patients and ensuring robust trial outcomes. Critical care was seen to lead in this, with our exemplar guidance used across all health research. We wish to revisit this guidance now that there is more experience of coenrolment in critical care trials. There is also more awareness of different consent models, such as deferred consent (taking consent when a person is awake and able to give consent) and consultee consent (asking families or independent professionals to consent). Consenting to coenrolment is an important ethical consideration for the revision of this guidance.

BackgroundCOVID-19 has become the most common cause of acute respiratory distress syndrome (ARDS) worldwide. Features of the pathophysiology and clinical presentation partially distinguish it from ‘classical’ ARDS. A Research and Development (RAND) analysis gauged the opinion of an expert panel about the management of ARDS with and without COVID-19 as the precipitating cause, using recent UK guidelines as a template.MethodsAn 11-person panel comprising intensive care practitioners rated the appropriateness of ARDS management options at different times during hospital admission, in the presence or absence of, or varying severity of SARS-CoV-2 infection on a scale of 1–9 (where 1–3 is inappropriate, 4–6 is uncertain and 7–9 is appropriate). A summary of the anonymised results was discussed at an online meeting moderated by an expert in RAND methodology. The modified online survey comprising 76 questions, subdivided into investigations (16), non-invasive respiratory support (18), basic intensive care unit management of ARDS (20), management of refractory hypoxaemia (8), pharmacotherapy (7) and anticoagulation (7), was completed again.ResultsDisagreement between experts was significant only when addressing the appropriateness of diagnostic bronchoscopy in patients with confirmed or suspected COVID-19. Adherence to existing published guidelines for the management of ARDS for relevant evidence-based interventions was recommended. Responses of the experts to the final survey suggested that the supportive management of ARDS should be the same, regardless of a COVID-19 diagnosis. For patients with ARDS with COVID-19, the panel recommended routine treatment with corticosteroids and a lower threshold for full anticoagulation based on a high index of suspicion for venous thromboembolic disease.ConclusionThe expert panel found no reason to deviate from the evidence-based supportive strategies for managing ARDS outlined in recent guidelines.

Introduction The probability of surviving a cardiac arrest remains low. International resuscitation guidelines state that extracorporeal cardiopulmonary resuscitation (ECPR) may have a role in selected patients suffering refractory cardiac arrest. Identifying these patients is challenging. This project systematically reviewed the evidence comparing the outcomes of ECPR over conventional-CPR (CCPR), before examining resuscitation-specific parameters to assess which patients might benefit from ECPR. Method Literature searches of studies comparing ECPR to CCPR and the clinical parameters of survivors of ECPR were performed. The primary outcome examined was survival at hospital discharge or 30 days. A secondary analysis examined the resuscitation parameters that may be associated with survival in patients who receive ECPR (no-flow and low-flow intervals, bystander-CPR, initial shockable cardiac rhythm, and witnessed cardiac arrest). Results Seventeen of 948 examined studies were included. ECPR demonstrated improved survival (OR 0.40 (0.27–0.60)) and a better neurological outcome (OR 0.10 (0.04–0.27)) over CCPR during literature review and meta-analysis. Characteristics that were associated with improved survival in patients receiving ECPR included an initial shockable rhythm and a shorter low-flow time. Shorter no-flow, the presence of bystander-CPR and witnessed arrests were not characteristics that were associated with improved survival following meta-analysis, although the quality of input data was low. All data were non-randomised, and hence the potential for bias is high. Conclusion ECPR is a sophisticated treatment option which may improve outcomes in a selected patient population in refractory cardiac arrest. Further comparative research is needed clarify the role of this potential resuscitative therapy.

Disclaimer: Veno-arterial extracorporeal membrane oxygenation (ECMO) is increasingly being deployed for selected patients in cardiac arrest who do not attain a native circulation with conventional CPR (ECPR). This ELSO guideline is intended to be a practical guide to implementing ECPR and the early management following establishment of ECMO support. Where a paucity of high-quality evidence exists, a consensus has been reached amongst the authors to provide guidance to the clinician. This guideline will be updated as further evidence in this field becomes available.

Background Out-of-hospital cardiac arrest carries a poor prognosis with survival less than 10% in many patient cohorts. Survival is inversely associated with duration of resuscitation as external chest compressions do not provide sufficient blood flow to prevent irreversible organ damage during a prolonged resuscitation. Extracorporeal membrane oxygenation (ECMO) instituted during cardiac arrest can provide normal physiological blood flows and is termed Extracorporeal Cardio-Pulmonary Resuscitation (ECPR). ECPR may improve survival when used with in-hospital cardiac arrests. This possible survival benefit has not been replicated in trials of out-of-hospital cardiac arrests, possibly because of the additional time it takes to transport the patient to hospital and initiate ECPR. Pre-hospital ECPR may shorten the time between cardiac arrest and physiological blood flows, potentially improving survival. It may also mitigate some of the neurological injury that many survivors suffer. Methods Sub30 is a prospective six patient feasibility study. The primary aim is to test whether it is possible to institute ECPR within 30 ​min of collapse in adult patients with refractory out of hospital cardiac arrest (OHCA). The secondary aims are to gather preliminary data on clinical outcomes, resource utilisation, and health economics associated with rapid ECPR delivery in order to plan any subsequent clinical investigation or clinical service. On study days a dedicated fast-response vehicle with ECPR capability will be tasked to out-of-hospital cardiac arrests in an area of London served by Barts Heart Centre. If patients suffer a cardiac arrest refractory to standard advanced resuscitation and meet eligibility criteria, ECPR will be started in the pre-hospital environment. Discussion Delivering pre-hospital ECPR within 30 ​min of an out-of-hospital cardiac arrest presents significant ethical, clinical, governance and logistical challenges. Prior to conducting an efficacy study of ECPR the feasibility of timely and safe application must be demonstrated first. Extensive planning, multiple high-fidelity multiagency simulations and a unique collaboration between pre-hospital and in-hospital institutions will allow us to test the feasibility of this intervention in London. The study has been reviewed, refined and endorsed by the International ECMO Network (ECMONet). Trial registration Clinicaltrials. gov NCT03700125 , prospectively registered October 9, 2018.

A 43-year-old man with Austrian syndrome, the triad of infective endocarditis (IE), pneumonia and meningitis caused by Streptococcus pneumoniae, underwent emergency aortic and mitral valve replacement and closure of an aortic root abscess. Postoperatively, he required mechanical circulatory support with veno-arterial extracorporeal membrane oxygenation and an intra-aortic balloon pump. Several days after surgery, new mitral and aortic paraprosthetic leaks (PPLs) developed. These were managed conservatively, initially, but eventually required percutaneous closure 6 weeks after the initial operation. This has enabled the patient to recover to independent mobility, 20 weeks after the operation. This case illustrates a rare clinical syndrome and the devastating impact of IE. Moreover, it illustrates the successful application of extracorporeal membrane oxygenation in postcardiotomy cardiac failure and the successful treatment of PPL in a patient unfit for redo surgery.

There is an increasing interest in using venoarterial extracorporeal membrane oxygenation (VA-ECMO) to manage out-of-hospital cardiac arrest, termed extracorporeal cardiopulmonary resuscitation (E-CPR).1 VA-ECMO, used in intensive care medicine for cardiorespiratory support, involves draining blood through a cannula sited in a large vein passage through a pump and a membrane oxygenator and returning it under pressure through another cannula sited in a large artery. The time between cardiac arrest and implementation of E-CPR is a major prognostic factor2 with data suggesting improved survival if instituted within 30 min.3 UK practice for out-of-hospital cardiac arrest involves advanced life support on scene for 20 min seeking return of spontaneous circulation and transport of appropriate patients to secondary care if initial efforts fail. Thus, if VA-ECMO is only commenced in hospital, eligible patients might not be stabilised until after 30 min, reducing the chance of neurologically intact survival. We performed a high-fidelity simulation to assess the possibility of implementing prehospital E-CPR for a simulated patient within 30 min of a call to emergency services and the logistics of transfer and handover to a heart attack centre. Our aim was to facilitate learning between prehospital, paramedic and ECMO teams to help coordinate future attempts at the intervention and plan a formal feasibility trial. We also hoped that this novel simulation would form a basis for future training in prehospital E-CPR. …

One of the few interventions to demonstrate improved outcomes for acute hypoxaemic respiratory failure is reducing tidal volumes when using mechanical ventilation, often termed lung protective ventilation. Veno-venous extracorporeal carbon dioxide removal (vv-ECCO2R) can facilitate reducing tidal volumes. pRotective vEntilation with veno-venouS lung assisT (REST) is a randomised, allocation concealed, controlled, open, multicentre pragmatic trial to determine the clinical and cost-effectiveness of lower tidal volume mechanical ventilation facilitated by vv-ECCO2R in patients with acute hypoxaemic respiratory failure. Patients requiring intubation and mechanical ventilation for acute hypoxaemic respiratory failure will be randomly allocated to receive either vv-ECCO2R and lower tidal volume mechanical ventilation or standard care with stratification by recruitment centre. There is a need for a large randomised controlled trial to establish whether vv-ECCO2R in acute hypoxaemic respiratory failure can allow the use of a more protective lung ventilation strategy and is associated with improved patient outcomes.

There is increasing interest in the potential use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) in the prehospital setting to stabilise patients in refractory cardiac arrest.1 VA-ECMO involves draining blood through a cannula sited in a large vein and passing it through a pump and a membrane oxygenator before returning it under pressure through another cannula sited in a large artery. It can therefore be used to temporarily replace the function of the heart and lungs. When VA-ECMO is used to manage refractory cardiac arrest, it is termed extracorporeal cardiopulmonary resuscitation (ECPR). Out-of-hospital cardiac arrest patients have poor outcomes,2 3 not least because it takes time to package and transport them to heart attack centres. By bringing VA-ECMO into the prehospital environment, it is hoped that vital organ perfusion can be re-established more quickly in a refractory cardiac arrest, preventing irreversible hypoxic organ damage and potentially improving out-of-hospital cardiac arrest survival rates that remain very low. Prehospital ECPR is fraught with difficulties and potential complications,4 many of which can be prepared for by simulation. Unfortunately, there are no cost-effective, commercially available manikins designed for ECPR. Previous attempts at simulating prehospital ECPR have used separate manikins for the dichotomous elements of cardiopulmonary resuscitation (CPR) and extracorporeal membrane oxygenation (ECMO); however, this significantly reduces the fidelity of the exercise. In-hospital ECMO manikins often have to forego the use of …

Extracorporeal carbon dioxide removal (ECCO2R) device technologies have enhanced the management of acute respiratory distress syndrome (ARDS) and other lung pathologies necessitating low tidal volume protective ventilation. We report the novel use of the interventional Lung Assist Membrane Ventilator® (iLA, Novalung GmbH) in a multi-trauma patient with pulmonary contusion and pre-existing cyanotic congenital heart disease and in a patient with raised intracranial pressure in the context of acute liver failure and primary graft non-function. In both cases, heart-lung interactions were complex, but AV-ECCO2R brought about significant improvements in respiratory indices and left/right ventricular function. The device facilitated restoration of homeostasis where other therapeutic options were limited or had failed.

BACKGROUND Intensive insulin therapy (IIT) has been shown to reduce mortality and morbidity in longer stay, critically ill patients. However, this has been demonstrated in a single site, whereas two multicentric studies have been terminated prematurely mainly due to hypoglycemia. Other difficulties with IIT include efficacy of glycemic control. This report describes how IIT can be improved by protocol simplification and removal of glucose supplementation. METHODS A clinical information system established at each bedspace guided staff through the IIT algorithms. Time spent within predefined glycemic ranges was calculated assuming a linear trend between successive measurements. Three groups were investigated retrospectively: IIT1 protocol,(1) an updated IIT2 version, and intuitive nurse dosing of conventional insulin therapy (CIT). RESULTS Fifty consecutive, critically ill patients were included in each study group. Patient characteristics were similar in each group. The frequency of CIT and IIT2 blood glucose measurements were 11.6 and 11.5 measurements per day, respectively, while the IIT1 measurements were more frequent (14.5 measurements per day). The mean proportion of time spent in the target glycemic range (4.4-6.1 mmol/liter) was highest in the IIT2 group (34.9%), as compared to the IIT1 (22.9%) and CIT groups (20.3%) (p

In the previous issue of Critical Care, Vermeulen Windsant and colleagues demonstrate that transfusion of packed red cells is associated with a transient increase in plasma free haemoglobin and scavenging of nitric oxide in vitro. They also demonstrate that older units of blood have more free haemoglobin in their supernatants. Whether the administration of older stored blood results in adverse clinical outcomes is a topical clinical question. The present study proposes a mechanism for transfusion-related harm but also has implications for patients who have other sources of free haemoglobin in their circulation.

Acute lung injury (ALI) and acute respiratory distress syndrome are characterized by protein rich alveolar edema, reduced lung compliance, and acute severe hypoxemia. A degree of pulmonary hypertension (PH) is also characteristic, higher levels of which are associated with increased morbidity and mortality. The increase in right ventricular (RV) afterload causes RV dysfunction and failure in some patients, with associated adverse effects on oxygen delivery. Although the introduction of lung protective ventilation strategies has probably reduced the severity of PH in ALI, a recent invasive hemodynamic analysis suggests that even in the modern era, its presence remains clinically important. We therefore sought to summarize current knowledge of the pathophysiology of PH in ALI.

Introduction and objectives Patients with pulmonary hypertension (PH) represent an extremely high-risk surgical group, with previous reported mortality 7–18%, and predicting perioperative risk is difficult. The aim of this study was to characterise a current cohort of patients with pulmonary hypertension undergoing surgery in a National UK Designated PH centre and to determine predictors of adverse events. Methods Consecutive patients with PH undergoing non-cardiac, non-obstetric surgery were identified by matching theatre and PH databases between 1st April 2008 and 1st April 2015. Demographics, recent echocardiogram, right heart catheterisation, B-natriuretic peptide (BNP), six-minute walk test (6MWT) and World Health Organisation functional class (WHO-FC) on last clinic visit was recorded. Anaesthetic and perioperative details; post-operative management, short-term morbidity and 28-day outcome were recorded. Data are mean±SD or median (range). Results 37 procedures requiring anaesthesia were identified in 32 patients with PAH (7 idiopathic PAH, 1 PVOD, 24 CHD-PAH, 4 CTD-PAH) and 1 CTEPH. Average age was 44.4 ± 13 years, 27(84%) were female. Baseline preoperative WHO-FC was II (3, 9%), III (28, 88%), IV (1, 3%). Baseline 6MWT distance was 317 ± 68 m; BNP 200 (12–2027) ng/L; RV systolic pressure (RVSP) 85 ± 16 mmHg, tricuspid annular planar systolic excursion (TAPSE) 18 ± 7 mm. Cases including oesophagogastroscopy (n = 4), dental extraction (n = 8) under general anaesthesia (GA) were classified as minor; 6 (16%) including mastectomy, laparotomy and fasciotomy as major surgical procedures. Almost all (95%) were performed under GA; most were elective procedures and were monitored on the high dependency or intensive care unit post-operatively. Cardiovascular perioperative complications occurred in 6 cases (16%) including death in 2 patients (5.4%) in the days following surgery, in both cases related to PH crises, resulting in right ventricular (RV) failure. Baseline parameters of RV function including RVSP, TAPSE and the presence of a pericardial effusion were associated with adverse events. Conclusion Perioperative mortality in patients with PH remains high, even in the current era. If surgery is deemed essential, PH centres with experts in cardiothoracic anaesthesia and ICU should be involved in preoperative planning with the PH multidisciplinary team guiding appropriate selection of patients, considering pulmonary haemodynamics and indices of RV function, as well as surgical factors.

Purpose To investigate differences in cytokine/chemokine release in response to lipoteichoic acid (LTA) or lipopolysaccharide (LPS) and contributing cellular mechanisms, in order to improve understanding of the pathogenesis of sepsis. Methods Levels of cytokines/chemokines were measured in plasma and peritoneal lavage fluid of 10-week-old male mice (C57/B16) following intraperitoneal injection of LTA or LPS (250 µg), and in supernatants of murine J774.2 cells, immortalised blood monocytes, or isolated human monocytes treated with LTA or LPS (0–10 µg/ml). The role of cytokine/chemokine messenger RNA (mRNA) stability versus nuclear factor-kappaB (NF-κB) and activator protein-1 (AP-1) in mediating cytokine/chemokine release in J774 cells was also assessed. Results In mice, plasma levels of keratinocyte-derived chemokine (KC), macrophage inflammatory protein (MIP)-2, interleukin (IL)-10, interferon (IFN)-γ and tumour necrosis factor-alpha (TNF-α) and peritoneal lavage fluid levels of KC, MIP-2 and TNF-α increased significantly 1 h after LPS. Only KC and MIP-2 levels increased 1 h after LTA. LPS-treated (10 μg/ml) J774 cells released MIP-2, IL-10, IFN-γ and TNF-α but not KC (24 h), whereas cells treated with 10 μg/ml LTA released only MIP-2. LPS-stimulated human monocytes released IL-10 and IL-8 (24 h); by contrast, LTA-treated cells released only IL-8. LPS and LTA activated NF-κB and AP-1 in J774 cells. The protein synthesis inhibitor cycloheximide abolished LPS-induced IL-10 mRNA expression and increased LTA- and LPS-induced mRNA for MIP-2 in J774 cells. Conclusion LTA and LPS, at clinically relevant concentrations, induced differential cytokine/chemokine release in vitro and in vivo, via effects distal to activation of NF-κB/AP-1 that might include chromatin remodelling or mRNA stability. Electronic supplementary material The online version of this article (doi:10.1007/s00134-011-2444-5) contains supplementary material, which is available to authorized users.

Extracorporeal membrane oxygenation (ECMO) can support gas exchange in patients with severe acute respiratory distress syndrome (ARDS), but its role has remained controversial. ECMO was used to treat patients with ARDS during the 2009 influenza A(H1N1) pandemic.To compare the hospital mortality of patients with H1N1-related ARDS referred, accepted, and transferred for ECMO with matched patients who were not referred for ECMO.A cohort study in which ECMO-referred patients were defined as all patients with H1N1-related ARDS who were referred, accepted, and transferred to 1 of the 4 adult ECMO centers in the United Kingdom during the H1N1 pandemic in winter 2009-2010. The ECMO-referred patients and the non-ECMO-referred patients were matched using data from a concurrent, longitudinal cohort study (Swine Flu Triage study) of critically ill patients with suspected or confirmed H1N1. Detailed demographic, physiological, and comorbidity data were used in 3 different matching techniques (individual matching, propensity score matching, and GenMatch matching).Survival to hospital discharge analyzed according to the intention-to-treat principle.Of 80 ECMO-referred patients, 69 received ECMO (86.3%) and 22 died (27.5%) prior to discharge from the hospital. From a pool of 1756 patients, there were 59 matched pairs of ECMO-referred patients and non-ECMO-referred patients identified using individual matching, 75 matched pairs identified using propensity score matching, and 75 matched pairs identified using GenMatch matching. The hospital mortality rate was 23.7% for ECMO-referred patients vs 52.5% for non-ECMO-referred patients (relative risk [RR], 0.45 [95% CI, 0.26-0.79]; P = .006) when individual matching was used; 24.0% vs 46.7%, respectively (RR, 0.51 [95% CI, 0.31-0.81]; P = .008) when propensity score matching was used; and 24.0% vs 50.7%, respectively (RR, 0.47 [95% CI, 0.31-0.72]; P = .001) when GenMatch matching was used. The results were robust to sensitivity analyses, including amending the inclusion criteria and restricting the location where the non-ECMO-referred patients were treated.For patients with H1N1-related ARDS, referral and transfer to an ECMO center was associated with lower hospital mortality compared with matched non-ECMO-referred patients.

Introduction Critically ill patients with diabetes are at increased risk for the development of complications, but the impact of diabetes on mortality is unclear. We conducted a systematic review and meta-analysis to determine the effect of diabetes on mortality in critically ill patients, making a distinction between different ICU types. Methods We performed an electronic search of MEDLINE and Embase for studies published from May 2005 to May 2010 that reported the mortality of adult ICU patients. Two reviewers independently screened the resultant 3,220 publications for information regarding ICU, in-hospital or 30-day mortality of patients with or without diabetes. The number of deaths among patients with or without diabetes and/or mortality risk associated with diabetes was extracted. When only crude survival data were provided, odds ratios (ORs) and standard errors were calculated. Data were synthesized using inverse variance with ORs as the effect measure. A random effects model was used because of anticipated heterogeneity. Results We included 141 studies comprising 12,489,574 patients, including 2,705,624 deaths (21.7%). Of these patients, at least 2,327,178 (18.6%) had diabetes. Overall, no association between the presence of diabetes and mortality risk was found. Analysis by ICU type revealed a significant disadvantage for patients with diabetes for all mortality definitions when admitted to the surgical ICU (ICU mortality: OR [95% confidence interval] 1.48 [1.04 to 2.11]; in-hospital mortality: 1.59 [1.28 to 1.97]; 30-day mortality: 1.62 [1.13 to 2.34]). In medical and mixed ICUs, no effect of diabetes on all outcomes was found. Sensitivity analysis showed that the disadvantage in the diabetic surgical population was attributable to cardiac surgery patients (1.77 [1.45 to 2.16], P < 0.00001) and not to general surgery patients (1.21 [0.96 to 1.53], P = 0.11). Conclusions Our meta-analysis shows that diabetes is not associated with increased mortality risk in any ICU population except cardiac surgery patients.

The case histories are presented of three adults who had severe hypercapnic acidosis despite mechanical ventilation with what were considered to be injurious tidal volumes and airway pressures. The use of a percutaneously inserted arteriovenous extracorporeal carbon dioxide removal (AV-ECCO(2)R) device facilitated a dramatic reduction in the amount of ventilatory support required, achieving a "lung-protective" level. Two patients survived to hospital discharge. One patient died after it became apparent that her late-stage interstitial lung disease was unresponsive to immunosuppression. AV-ECCO(2)R may be a useful strategy in facilitating lung-protective ventilation.

The systemic inflammatory response syndrome (SIRS) is the leading cause of morbidity & mortality in the critically ill. It is associated with a 50% reduction in 5 year life expectancy. SIRS is defined as 2 of the following criteria: heart rate >90, respiratory rate >20 or pCO 2 38°C, white cell count 12 x10 9 /l. These criteria are used to stratify patients for specific therapies & in research to define interventional groups. Cardiac surgery is associated with systemic inflammation. The validity of the SIRS criteria have never been formally evaluated post cardiac surgery. We undertook to describe the incidence of SIRS post cardiac surgery & relate this to outcome. Methods: We retrospectively analysed prospectively collected data from 2764 consecutive admissions following cardiac surgery (coronary bypass grafting 1425, valve surgery 763, combined procedure 252, other 324). The number of criteria met simultaneously within 1 hour epochs was recorded for the entire admissions. Results: 96.4%, 57.9% & 12.2% of patients met at least 2, 3 or 4 criteria respectively within 24hrs of admission. The temperature criterion was least often fulfilled. ICU mortality was 2.67%. Length of stay exceeded 3 days in 18.5% of patients. The capacity of the criteria to predict mortality & prolonged ICU stay is presented in the table . Discussion: Nearly all patients fulfilled the standard 2 criteria definition of SIRS within 24hrs of admission. This definition does not adequately define the subgroup of patients with greater systemic inflammation, mortality or length of stay. Thus, some clinical manifestations of inflammation are very common following cardiac surgery, although not necessarily prognostic. By contrast, the presence of 3 or more criteria was more discriminatory of death & prolonged ICU stay. We propose that 3 or more SIRS criteria is a more appropriate threshold that defines those patients with clinically significant inflammation post cardiac surgery.

Use of inhaled nitric oxide for treatment of pulmonary hypertension in adult critical illness is limited by its mode of delivery and high costs, prompting evaluation of alternative therapies. We report the use of oral sildenafil in a patient with severe secondary pulmonary hypertension and right ventricular dysfunction. Following reduction in mean pulmonary artery pressure and pulmonary vascular resistance with inhaled nitric oxide, crossover to sildenafil therapy maintained control of pulmonary hypertension, facilitating discontinuation of respiratory and cardiovascular organ support. The relative pulmonary vascular specificity of oral sildenafil, and its low cost, makes it an attractive therapeutic alternative to inhaled nitric oxide, and warrants further study.

Lethal necrotizing fasciitis caused by Streptococcus pyogenes is characterized by a paucity of neutrophils at the site of infection. Interleukin (IL)-8, which is important for neutrophil transmigration and activation, can be degraded by S. pyogenes. Blood isolates of S. pyogenes were better able to degrade human IL-8 than throat isolates. Degradation of IL-8 was the result of a single specific cleavage between 59glutamine and 60arginine within the IL-8 C-terminal alpha helix. Cleaved IL-8 reduced neutrophil activation and migration. IL-8-cleaving activity was found in partially purified supernatant of a necrotizing fasciitis isolate, and this activity was associated with an approximately 150-kDa fraction containing S. pyogenes cell envelope proteinase (SpyCEP). IL-8-cleaving activity corresponded with the presence of SpyCEP in the supernatant. Cleavage of IL-8 by S. pyogenes represents an unprecedented mechanism of immune evasion, effectively preventing IL-8 C-terminus-mediated endothelial translocation and subsequent recruitment of neutrophils.

Introduction It is recognized that administration of insulin with glucose decreases catabolic response in sepsis. The aim of the present study was to compare the effects of two levels of insulinaemia on glucose metabolism and energy expenditure in septic patients and volunteers. Methods Glucose uptake, oxidation and storage, and energy expenditure were measured, using indirect calorimetry, in 20 stable septic patients and 10 volunteers in a two-step hyperinsulinaemic (serum insulin levels 250 and 1250 mIU/l), euglycaemic (blood glucose concentration 5 mmol/l) clamp. Differences between steps of the clamp (from serum insulin 1250 to 250 mIU/l) for all parameters were calculated for each individual, and compared between septic patients and volunteers using the Wilcoxon nonpaired test. Results Differences in glucose uptake and storage were significantly less in septic patients. The differences in glucose oxidation between the groups were not statistically significant. Baseline energy expenditure was significantly higher in septic patients, and there was no significant increase in either step of the clamp in this group; when comparing the two groups, the differences between steps were significantly greater in volunteers. Conclusion A hyperdynamic state of sepsis leads to a decrease in glucose uptake and storage in comparison with healthy volunteers. An increase in insulinaemia leads to an increase in all parameters of glucose metabolism, but the increases in glucose uptake and storage are significantly lower in septic patients. A high level of insulinaemia in sepsis increases glucose uptake and oxidation significantly, but not energy expenditure, in comparison with volunteers.

Expectations of modern healthcare are extremely high. Medicine can achieve wonders hardly dreamt of 50 years ago. Technology and the accelerated pace of change threaten to displace compassion. That old phrase which used to resonate when used by consultants on ward rounds, ‘lots of TLC, Sister’ is rarely heard now. Healthcare is expensive and every nation wrestles with its priorities and problems. The urge to measure is understandable and necessary and has led to positive results such as the marked reduction in waiting times for treatment in hospital within the NHS. And yet, much of what is really valuable to our patients is difficult to measure. Prompted by our Director of Nursing and supported by King's Fund we have embarked on the Schwartz Rounds.1 The Royal Brompton and Harefield are the third hospital Trust in the UK to do so after Cheltenham and Gloucester and the Royal Free Hospitals. As a postgraduate teaching institution, the Royal Brompton and Harefield NHS Foundation Trust aspires to care, at the highest level, for patients with heart and lung disease. We endeavour to manage difficult clinical problems that others cannot. In this process it is easy to get lost in the logistics of efficiency and innovation and to ignore the human relationships that develop between both staff and their patients and between different staff members. Ken Schwartz was a successful American lawyer in his early 40s when he was struck down with lung cancer. He was treated at the Brigham and Women's Hospital, Boston some 11 years ago. Despite all attempts at treatment he died 11 months after the initial diagnosis was made. He and his family had nothing but praise for the care he received at an internationally renowned centre. They realized also the importance of their relationships with the caregivers. Indeed, in an essay in the Boston Globe, Ken Schwartz wrote that ‘the smallest acts of kindness made the unbearable bearable’. The family set up a legacy to enable monthly meetings, Schwartz Rounds, to take place where individual staff members could feel free and safe to express and understand their feelings about the care of a particular patient. The Rounds aim to nurture the relationships between patients and all members of staff within an institution. Everyone is welcomed to the Schwartz Rounds – porters, catering staff, pharmacists, librarians, scientists, managers and administrators. It is not just for doctors, nurses and therapists. Many of us were brought up in an age when the metaphorical stiff upper lip still held sway. While we were allowed to have ‘feelings’ we were discouraged from ‘wearing them on our sleeve’. As busy practising physicians, anaesthetists and surgeons, we inevitably have taken on the treatment of extremely sick patients whose time in hospital, despite very high levels of effort, ended with the death of the patient. Delivering bad news to relatives and loved ones is never easy but is very important and, in a way, helps to lighten the load on oneself. In the past, we might slink away, sleep uneasily for the next few nights and be somewhat withdrawn with our friends, partners and spouses. Alternatively, we may have debriefed with colleagues over a drink after the work day had ended – a situation now less common with the loosening of work ties associated with the reduced hours necessitated by the European Working Time Directive. But, showing compassion towards oneself is crucial if we are to continue showing compassion towards patients and their families. By taking time to debrief as a team and discuss what the experience of caring for a critically-ill patient was like, we can guard against the long-term effects of the stress of such challenging situations.2 Schwartz Rounds are one-hour meetings held in the middle of the day, preceded by a buffet lunch, a principle laid down by Ken Schwartz himself. A story is told by three or four people, of whom only one is a doctor. Each person speaks for three to four minutes about the care of a particular patient. There is no formal presentation. The rest of the room are invited to join the discussion by a facilitator, who is a senior nurse, and the lead clinician, a senior doctor. The presentation and discussion are confidential, and strenuous efforts are made to ensure that we preserve the anonymity of the patient. The Rounds stop promptly after 60 minutes. We have noticed that many of the audience linger afterwards to continue the discussions in smaller groups. We take this as one indicator that these Rounds are helpful. Preliminary analysis of the evaluation forms also suggests that there is considerable enthusiasm for these sessions. A few hours of preparation are required in the weeks leading up to the round and we have found that a ‘dress rehearsal’ on the morning of the Round is very helpful. It helps to highlight the key issues and provides leads to the subsequent discussion. We are about to embark on a prospective study to assess the impact of these Rounds not only on the panel members but on the audience, the hospital at large, and the patients. Meetings of this type are an effective way of providing the care team with an outlet to share their feelings with each other. This can help staff to understand that they are supported, their feelings are mirrored by others and that they are not isolated. It helps them to continue providing quality care even in highly emotional cases. Moreover, several participants have remarked that the process of preparation for these sessions has helped them to achieve closure on a troubling experience that had been niggling in their consciousness for many months. Six months into our Schwartz Rounds we are learning fast and have been helped enormously by the skill of a professional psychologist who acts both as our coach and quality controller. In any meeting of medical people the overwhelming desire is to try to solve the problem and focus entirely on the patient. These Rounds are different. We seek to bring problems of care into the fresh air, a process which requires a great deal of courage on the part of the participants. This process is not sterile but leads those in a position of power in the hospital to re-think the way we organize ourselves and seek to find better solutions. The true heroes of our hospitals are not the nurses or the doctors but the patients. Most patients are just ordinary people thrust into extraordinary circumstances and part of what enables them to be courageous is the compassion of those caring for them. It behoves us then to care for ourselves so that we can better care for our patients.

The idea of employing cardiopulmonary bypass technology as a means of oxygenating (extracorporeal membrane oxygenation (ECMO)) or removing carbon dioxide (ECCO2R) in patients with acute respiratory failure (ARF) was first assessed in randomised controlled trials in the 1970s and 1980s.1 2 Poor rates of survival and major complications, particularly massive haemorrhage, led to most intensivists believing that ECMO was inappropriate in adults. A small number of centres worldwide—including that in Leicester, UK—continued to refine the use of ECMO in small numbers of adult patients whom it proved impossible to oxygenate by conventional means. Following the publication of their case series with improved results,3 Peek and colleagues embarked upon a randomised controlled trial of conventional ventilation or ECMO in patients with severe ARF (CESAR), the results of which have just been reported.4 Patients (n=766) were screened for inclusion over a 5-year period and those with potentially reversible severe ARF (defined as a Murray score >3 or …

Patient satisfaction data collation is a priority for the UK's Care Quality Commission. In the adult intensive care unit (AICU), patients are often sedated for prolonged periods. Family satisfaction data may be useful to gauge quality of service delivery. The Family Satisfaction-ICU (FS-ICU 34) questionnaire was developed and validated in the USA [1]. To our knowledge, we are the first group to use it in the UK.

Catheter-related bloodstream infection (CRBSI) accounts for 10% to 20% of hospital-acquired infections in the UK and is associated with both increased ICU stay and mortality. Rates of CRBSI may be modified by clinical care during insertion and utilisation of central venous catheters (CVCs) [1]. As such, the incidence of CRBSI has been proposed as a quality indicator. There is currently no consensus regarding the definition of CRBSI.

Systemic inflammatory response syndrome (SIRS) is the leading cause of morbidity and mortality in the critically ill. It is associated with a 50% reduction in 5-year life expectancy. SIRS is defined as two of the following criteria: heart rate >90 beats/min, respiratory rate >20 breaths/min or pCO2 38°C, white cell count 12 × 109/l. These criteria are used to stratify patients for specific therapies and in research to define interventional groups. Cardiac surgery is associated with systemic inflammation. We undertook to describe the incidence of SIRS post cardiac surgery and relate this to outcome.

International guidelines concerning the management of patients with sepsis, septic shock and multiple organ failure make no reference to the nature of the infecting organism. Indeed, most clinical signs of sepsis are nonspecific. In contrast, in vitro data suggest that there are mechanistic differences between bacterial, viral and fungal sepsis, and imply that pathogenetic differences may exist between subclasses such as Gram-negative and Gram-positive bacteria. These differences are reflected in different cytokine profiles and mortality rates associated with Gram-positive and Gram-negative sepsis in humans. They also suggest that putative anti-mediator therapies may act differently according to the nature of an infecting organism. Data from some clinical trials conducted in severe sepsis support this hypothesis. It is likely that potential new therapies targeting, for example, Toll-like receptor pathways will require knowledge of the infecting organism. The advent of new technologies that accelerate the identification of infectious agents and their antimicrobial sensitivities may allow better tailored anti-mediator therapies and administration of antibiotics with narrow spectra and known efficacy.

Background Little is known about the development of acute lung injury outside the intensive care unit. We set out to document the following: the association between predefined clinical conditions and the development of acute lung injury by using the American–European consensus definition; the frequency of lung injury development outside the intensive care unit; and the temporal relationship between antecedent clinical risk conditions, intensive care admission, and diagnosis of lung injury. Methods We conducted a 4-month prospective observational study in three Spanish teaching hospitals, enrolling consecutive patients who developed clinical conditions previously linked to lung injury, both inside and outside the intensive care unit. Patients were followed prospectively for outcomes, including the diagnosis of acute lung injury or acute respiratory distress syndrome. Results A total 815 patients were identified with at least one clinical insult; the most common were sepsis, pneumonia, and pancreatitis. Pulmonary risk conditions were observed in 30% of cases. Fifty-three patients (6.5%) developed acute lung injury; 33 of these (4.0%) met criteria for acute respiratory distress syndrome. Lung injury occurred most commonly in the setting of sepsis (46/53; 86.7%), but shock (21/59; 36%) and pneumonia (20/211; 9.5%) portended the highest proportional risk; this risk was higher in patients with increasing numbers of clinical risk conditions (2.2%, 14%, and 21% (P < 0.001) in patients with one, two, and three conditions, respectively). Median days (interquartile range) from risk condition to diagnosis of lung injury was shorter with pulmonary (0 (0 to 2)) versus extrapulmonary (3 (1 to 5)) (P = 0.029) risk conditions. Admission to the intensive care unit was provided to 9/20 (45%) patients with acute lung injury and to 29/33 (88%) of those with acute respiratory distress syndrome. Lung injury patients had higher mortality than others (acute lung injury 25.0%; acute respiratory distress syndrome 45.5%; others 10.3%; P < 0.001). Conclusion The time course from clinical insult to diagnosis of lung injury was rapid, but may be longer for extrapulmonary cases. Some patients with lung injury receive care and die outside the intensive care unit; this observation needs further study.

Introduction A single centre has reported that implementation of an intensive insulin protocol, aiming for tight glycaemic control (blood glucose 4.4 to 6.1 mmol/l), resulted in significant reduction in mortality in longer stay medical and surgical critically ill patients. Our aim was to determine the degree to which tight glycaemic control can be maintained using an intensive insulin therapy protocol with computerized decision support and to identify factors that may be associated with the degree of control. Methods At a general adult 22-bed intensive care unit, we implemented an intensive insulin therapy protocol in mechanically ventilated patients, aiming for a target glucose range of 4.4 to 6.1 mmol/l. The protocol was integrated into the computerized information management system by way of a decision support program. The time spent in each predefined blood glucose band was estimated, assuming a linear trend between measurements. Results Fifty consecutive patients were investigated, involving analysis of 7,209 blood glucose samples, over 9,214 hours. The target tight glycaemic control band (4.4 to 6.1 mmol/l) was achieved for a median of 23.1% of the time that patients were receiving intensive insulin therapy. Nearly half of the time (median 48.5%), blood glucose was within the band 6.2 to 7.99 mmol/l. Univariate analysis revealed that body mass index (BMI), Acute Physiology and Chronic Health Evaluation (APACHE) II score and previous diabetes each explained approximately 10% of the variability in tight glycaemic control. BMI and APACHE II score explained most (27%) of the variability in tight glycaemic control in the multivariate analysis, after adjusting for age and previous diabetes. Conclusion Use of the computerized decision supported intensive insulin therapy protocol did result in achievement of tight glycaemic control for a substantial percentage of each patient's stay, although it did deliver 'normoglycaemia' (4.4 to about 8 mmol/l) for nearly 75% of the time. Tight glycaemic control was difficult to achieve in critically ill patients using this protocol. More sophisticated methods such as continuous blood glucose monitoring with automated insulin and glucose infusion adjustment may be a more effective way to achieve tight glycaemic control. Glycaemia in patients with high BMI and APACHE II scores may be more difficult to control using intensive insulin therapy protocols. Trial registration number 05/Q0505/1.

Rusavy and colleagues recently endeavoured to dissect out the metabolic effects of insulin in patients with severe sepsis, in the setting of normoglycaemia. Twenty stable patients were studied 3–7 days after admission using a euglycaemic clamp at two supraphysiological insulin levels. Increased doses of exogenous insulin caused preferential use of glucose as a metabolic substrate, while total energy expenditure remained constant. Consequently, hyperinsulinaemia reduced tissue oxygen demand and catabolism of protein in patients with sepsis; the benefits of these effects are not proven. The effects of insulin at different time points in sepsis were not examined.

ContextHyperglycemia is common in critically ill patients, even in those without diabetes mellitus. Aggressive glycemic control may reduce mortality in this population. However, the relationship between mortality, the control of hyperglycemia, and the administration of exogenous insulin is unclear.ObjectiveTo determine whether blood glucose level or quantity of insulin administered is associated with reduced mortality in critically ill patients.Design, Setting, and PatientsSingle-center, prospective, observational study of 531 patients (median age, 64 years) newly admitted over the first 6 months of 2002 to an adult intensive care unit (ICU) in a UK national referral center for cardiorespiratory surgery and medicine.Main Outcome MeasuresThe primary end point was intensive care unit (ICU) mortality. Secondary end points were hospital mortality, ICU and hospital length of stay, and predicted threshold glucose level associated with risk of death.ResultsOf 531 patients admitted to the ICU, 523 underwent analysis of their glycemic control. Twenty-four–hour control of blood glucose levels was variable. Rates of ICU and hospital mortality were 5.2% and 5.7%, respectively; median lengths of stay were 1.8 (interquartile range, 0.9-3.7) days and 6 (interquartile range, 4.5-8.3) days, respectively. Multivariable logistic regression demonstrated that increased administration of insulin was positively and significantly associated with ICU mortality (odds ratio, 1.02 [95% confidence interval, 1.01-1.04] at a prevailing glucose level of 111-144 mg/dL [6.1-8.0 mmol/L] for a 1-IU/d increase), suggesting that mortality benefits are attributable to glycemic control rather than increased administration of insulin. Also, the regression models suggest that a mortality benefit accrues below a predicted threshold glucose level of 144 to 200 mg/dL (8.0-11.1 mmol/L), with a speculative upper limit of 145 mg/dL (8.0 mmol/L) for the target blood glucose level.ConclusionsIncreased insulin administration is positively associated with death in the ICU regardless of the prevailing blood glucose level. Thus, control of glucose levels rather than of absolute levels of exogenous insulin appear to account for the mortality benefit associated with intensive insulin therapy demonstrated by others.

Introduction Pulmonary vascular dysfunction, pulmonary hypertension (PH), and resulting right ventricular (RV) failure occur in many critical illnesses and may be associated with a worse prognosis. PH and RV failure may be difficult to manage: principles include maintenance of appropriate RV preload, augmentation of RV function, and reduction of RV afterload by lowering pulmonary vascular resistance (PVR). We therefore provide a detailed update on the management of PH and RV failure in adult critical care. Methods A systematic review was performed, based on a search of the literature from 1980 to 2010, by using prespecified search terms. Relevant studies were subjected to analysis based on the GRADE method. Results Clinical studies of intensive care management of pulmonary vascular dysfunction were identified, describing volume therapy, vasopressors, sympathetic inotropes, inodilators, levosimendan, pulmonary vasodilators, and mechanical devices. The following GRADE recommendations (evidence level) are made in patients with pulmonary vascular dysfunction: 1) A weak recommendation (very-low-quality evidence) is made that close monitoring of the RV is advised as volume loading may worsen RV performance; 2) A weak recommendation (low-quality evidence) is made that low-dose norepinephrine is an effective pressor in these patients; and that 3) low-dose vasopressin may be useful to manage patients with resistant vasodilatory shock. 4) A weak recommendation (low-moderate quality evidence) is made that low-dose dobutamine improves RV function in pulmonary vascular dysfunction. 5) A strong recommendation (moderate-quality evidence) is made that phosphodiesterase type III inhibitors reduce PVR and improve RV function, although hypotension is frequent. 6) A weak recommendation (low-quality evidence) is made that levosimendan may be useful for short-term improvements in RV performance. 7) A strong recommendation (moderate-quality evidence) is made that pulmonary vasodilators reduce PVR and improve RV function, notably in pulmonary vascular dysfunction after cardiac surgery, and that the side-effect profile is reduced by using inhaled rather than systemic agents. 8) A weak recommendation (very-low-quality evidence) is made that mechanical therapies may be useful rescue therapies in some settings of pulmonary vascular dysfunction awaiting definitive therapy. Conclusions This systematic review highlights that although some recommendations can be made to guide the critical care management of pulmonary vascular and right ventricular dysfunction, within the limitations of this review and the GRADE methodology, the quality of the evidence base is generally low, and further high-quality research is needed.