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Hyperglycaemia is common in hospitalized individuals, and is often caused by physiological stress associated with critical illness or major surgery. Insulin therapy is an established treatment for hyperglycaemia and acute hyperkalaemia, and has also been used for myocardial dysfunction resistant to inotropic support. Insulin is commonly used in both organ donors and transplant recipients for hyperglycaemia, but the underlying knowledge base supporting its use remains limited. Insulin therapy plays an important yet poorly understood role in both organ donation and transplantation. Tight glycaemic control has been extensively studied in critical care over the past 15 years; however, this has not yet translated into the field of transplantation, where patients are more unwell and where improved outcomes remain an ongoing challenge. Insulin therapy and optimization of glycaemic control represent important areas for future hypothesis-driven research into organ donation and transplantation, such as amelioration of ischaemia-reperfusion injury, rejection and infection.

Background Ventilator-associated pneumonia (VAP) is associated with significant healthcare cost, morbidity, and mortality, but can be difficult to identify, resulting in over-diagnosis and excessive use of broad-spectrum antimicrobial therapy. In addition, some organisms commonly cultured from the airways of critically ill patients, in particular Candida species, are of unknown clinical significance. Methods A prospective cohort study was conducted across five intensive care units in the North-West of England. Participants were enrolled within 24 hours of commencing antimicrobial therapy for suspected VAP. Laboratory-confirmed VAP was defined by quantitative culture of a known pneumonia-causing pathogen above predetermined growth thresholds. Univariate logistic regression was used to determine the impact of laboratory-confirmed VAP, APACHE II, culture of Staphylococcus aureus, and culture of Candida species on 30-day mortality. Results The prevalence of laboratory-confirmed VAP was 43/96 (44%), and the median number of antimicrobials prescribed for VAP was 1 (range: 1-4). Candida species were identified in 32/96 patients (33%). The overall 30-day mortality was 22/96 (26%). None of the variables analysed were associated with 30-day mortality, except for culture of Candida species, which was associated with survival (odds ratio 0.26, 95% CI 0.07 to 0.98; p= 0.047). Conclusions Ventilator-associated pneumonia was confirmed in under half the patients commenced on antimicrobial therapy for suspected VAP, which highlights the urgent need for improved diagnostic strategies. In our clinical practice, Candida species are not treated as pathogenic in VAP, and in this study, growth of Candida species was not associated with excess 30-day mortality.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability.

Background Trainee research collaboratives (TRCs) have pioneered high quality, prospective ‘snap-shot’ surgical cohort studies in the UK. Outcomes After Kidney injury in Surgery (OAKS) was the first TRC cohort study to attempt to collect one-year follow-up data. The aims of this study were to evaluate one-year follow-up and data completion rates, and to identify factors associated with improved follow-up rates. Methods In this multicentre study, patients undergoing major gastrointestinal surgery were prospectively identified and followed up at one-year following surgery for six clinical outcomes. The primary outcome for this report was the follow-up rate for mortality at 1 year. The secondary outcome was the data completeness rate in those patients who were followed-up. An electronic survey was disseminated to investigators to identify strategies associated with improved follow-up. Results Of the 173 centres that collected baseline data, 126 centres registered to participate in one-year follow-up. Overall 62.3% (3482/5585) of patients were followed-up at 1 year; in centres registered to collect one-year outcomes, the follow-up rate was 82.6% (3482/4213). There were no differences in sex, comorbidity, operative urgency, or 7-day postoperative AKI rate between patients who were lost to follow-up and those who were successfully followed-up. In centres registered to collect one-year follow-up outcomes, overall data completeness was 83.1%, with 57.9% (73/126) of centres having ≥95% data completeness. Factors associated with increased likelihood of achieving ≥95% data completeness were total number of patients to be followed-up (77.4% in centres with 60 patients, p = 0.030), and central versus local storage of patient identifiers (72.5% vs 48.0%, respectively, p = 0.006). Conclusions TRC methodology can be used to follow-up patients identified in prospective cohort studies at one-year. Follow-up rates are maximized by central storage of patient identifiers.

Background: Ventilator-associated pneumonia is the most common intensive care unit (ICU)-acquired infection, yet accurate diagnosis remains difficult, leading to overuse of antibiotics. Low concentrations of IL-1β and IL-8 in bronchoalveolar lavage fluid have been validated as effective markers for exclusion of ventilator-associated pneumonia. The VAPrapid2 trial aimed to determine whether measurement of bronchoalveolar lavage fluid IL-1β and IL-8 could effectively and safely improve antibiotic stewardship in patients with clinically suspected ventilator-associated pneumonia.Methods: VAPrapid2 was a multicentre, randomised controlled trial in patients admitted to 24 ICUs from 17 National Health Service hospital trusts across England, Scotland, and Northern Ireland. Patients were screened for eligibility and included if they were 18 years or older, intubated and mechanically ventilated for at least 48 h, and had suspected ventilator-associated pneumonia. Patients were randomly assigned (1:1) to biomarker-guided recommendation on antibiotics (intervention group) or routine use of antibiotics (control group) using a web-based randomisation service hosted by Newcastle Clinical Trials Unit. Patients were randomised using randomly permuted blocks of size four and six and stratified by site, with allocation concealment. Clinicians were masked to patient assignment for an initial period until biomarker results were reported. Bronchoalveolar lavage was done in all patients, with concentrations of IL-1β and IL-8 rapidly determined in bronchoalveolar lavage fluid from patients randomised to the biomarker-based antibiotic recommendation group. If concentrations were below a previously validated cutoff, clinicians were advised that ventilator-associated pneumonia was unlikely and to consider discontinuing antibiotics. Patients in the routine use of antibiotics group received antibiotics according to usual practice at sites. Microbiology was done on bronchoalveolar lavage fluid from all patients and ventilator-associated pneumonia was confirmed by at least 104 colony forming units per mL of bronchoalveolar lavage fluid. The primary outcome was the distribution of antibiotic-free days in the 7 days following bronchoalveolar lavage. Data were analysed on an intention-to-treat basis, with an additional per-protocol analysis that excluded patients randomly assigned to the intervention group who defaulted to routine use of antibiotics because of failure to return an adequate biomarker result. An embedded process evaluation assessed factors influencing trial adoption, recruitment, and decision making. This study is registered with ISRCTN, ISRCTN65937227, and ClinicalTrials.gov, NCT01972425.Findings: Between Nov 6, 2013, and Sept 13, 2016, 360 patients were screened for inclusion in the study. 146 patients were ineligible, leaving 214 who were recruited to the study. Four patients were excluded before randomisation, meaning that 210 patients were randomly assigned to biomarker-guided recommendation on antibiotics (n=104) or routine use of antibiotics (n=106). One patient in the biomarker-guided recommendation group was withdrawn by the clinical team before bronchoscopy and so was excluded from the intention-to-treat analysis. We found no significant difference in the primary outcome of the distribution of antibiotic-free days in the 7 days following bronchoalveolar lavage in the intention-to-treat analysis (p=0·58). Bronchoalveolar lavage was associated with a small and transient increase in oxygen requirements. Established prescribing practices, reluctance for bronchoalveolar lavage, and dependence on a chain of trial-related procedures emerged as factors that impaired trial processes.Interpretation: Antibiotic use remains high in patients with suspected ventilator-associated pneumonia. Antibiotic stewardship was not improved by a rapid, highly sensitive rule-out test. Prescribing culture, rather than poor test performance, might explain this absence of effect.Funding: UK Department of Health and the Wellcome Trust.

Acidosis is a common feature of patients referred to critical care from the emergency department. We present the case of a 49-year-old female with multi-organ dysfunction syndrome (MODS) and an arterial pH of 6.685 on arrival to the emergency department. This case is unique as the patient was in circulatory shock with MODS from rhabdomyolysis on arrival and had not suffered a cardiac arrest. We believe this to be the first reported case of full recovery from such an extreme metabolic disturbance in this context, and discuss the relevance of profound acidosis to early clinical decision-making.

This study aimed to determine the impact of preoperative exposure to intravenous contrast for CT and the risk of developing postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery.This prospective, multicentre cohort study included adults undergoing gastrointestinal resection, stoma reversal or liver resection. Both elective and emergency procedures were included. Preoperative exposure to intravenous contrast was defined as exposure to contrast administered for the purposes of CT up to 7 days before surgery. The primary endpoint was the rate of AKI within 7 days. Propensity score-matched models were adjusted for patient, disease and operative variables. In a sensitivity analysis, a propensity score-matched model explored the association between preoperative exposure to contrast and AKI in the first 48 h after surgery.A total of 5378 patients were included across 173 centres. Overall, 1249 patients (23·2 per cent) received intravenous contrast. The overall rate of AKI within 7 days of surgery was 13·4 per cent (718 of 5378). In the propensity score-matched model, preoperative exposure to contrast was not associated with AKI within 7 days (odds ratio (OR) 0·95, 95 per cent c.i. 0·73 to 1·21; P = 0·669). The sensitivity analysis showed no association between preoperative contrast administration and AKI within 48 h after operation (OR 1·09, 0·84 to 1·41; P = 0·498).There was no association between preoperative intravenous contrast administered for CT up to 7 days before surgery and postoperative AKI. Risk of contrast-induced nephropathy should not be used as a reason to avoid contrast-enhanced CT.El objetivo de este estudio fue determinar el impacto de la exposición preoperatoria al contraste intravenoso para la tomografía computarizada (TC) y el riesgo de desarrollar insuficiencia renal aguda (IRA) postoperatoria en pacientes sometidos a cirugía gastrointestinal mayor. MÉTODOS: Este estudio de cohorte prospectivo y multicéntrico incluyó adultos sometidos a una resección gastrointestinal, cierre de estoma o resección hepática. Se incluyeron tanto procedimientos electivos como urgentes. La exposición al contraste intravenoso preoperatorio se definió como la administración de contraste para la realización de una TC durante los 7 días previos a la cirugía. El criterio de valoración principal fue la tasa de IRA a los 7 días. Se utilizaron modelos de puntuación de propensión emparejados (propensity score matched, PSM) ajustados por paciente, enfermedad y variables operatorias. Los resultados del modelo se presentan como razón de oportunidades (odds ratio, OR) e i.c. del 95%. En un análisis de sensibilidad, se examinó la asociación entre la exposición preoperatoria al contraste y la IRA en las primeras 48 horas después de la cirugía mediante un modelo de PSM.Se incluyeron un total de 5.378 pacientes de 173 centros. Globalmente, el 23,2% (n = 1.249) de los pacientes recibieron medios de contraste intravenosos. La tasa global de IRA postoperatoria a los 7 días fue del 13,4% (718/5.378). En el modelo de puntuación de propensión emparejado, la exposición preoperatoria al contraste no se asoció con IRA a los 7 días (OR 0,95; i.c. del 95%: 0,73-1,21; P = 0,669). En el análisis de sensibilidad no se observó una asociación entre la administración de contraste preoperatorio y la IRA postoperatoria a las 48 horas (OR 1,09; i.c. del 95% 0,84-1,41; P = 0,498). CONCLUSIÓN: No hubo asociación entre la administración preoperatoria de contraste intravenoso para tomografías computarizadas durante los 7 días previos a la cirugía y la IRA postoperatoria. El riesgo de nefropatía inducida por el contraste no debe usarse de manera rutinaria como una razón para evitar la práctica de un TC con contraste.

The peri‐operative use of angiotensin‐converting enzyme inhibitors or angiotensin‐2 receptor blockers is thought to be associated with an increased risk of postoperative acute kidney injury. To reduce this risk, these agents are commonly withheld during the peri‐operative period. This study aimed to investigate if withholding angiotensin‐converting enzyme inhibitors or angiotensin‐2 receptor blockers peri‐operatively reduces the risk of acute kidney injury following major non‐cardiac surgery. Patients undergoing elective major surgery on the gastrointestinal tract and/or the liver were eligible for inclusion in this prospective study. The primary outcome was the development of acute kidney injury within seven days of operation. Adjusted multi‐level models were used to account for centre‐level effects and propensity score matching was used to reduce the effects of selection bias between treatment groups. A total of 949 patients were included from 160 centres across the UK and Republic of Ireland. From this population, 573 (60.4%) patients had their angiotensin‐converting enzyme inhibitors or angiotensin‐2 receptor blockers withheld during the peri‐operative period. One hundred and seventy‐five (18.4%) patients developed acute kidney injury; there was no difference in the incidence of acute kidney injury between patients who had their angiotensin‐converting enzyme inhibitors or angiotensin‐2 receptor blockers continued or withheld (107 (18.7%) vs. 68 (18.1%), respectively; p = 0.914). Following propensity matching, withholding angiotensin‐converting enzyme inhibitors or angiotensin‐2 receptor blockers did not demonstrate a protective effect against the development of postoperative acute kidney injury (OR (95%CI) 0.89 (0.58–1.34); p = 0.567).

The kidneys play a central role in the homeostasis of fluid, electrolyte and acid–base balance, whilst ensuring the efficient excretion of water-soluble waste products. They also have ancillary functions such as the production of erythropoietin, their crucial contribution to vitamin D metabolism and their neuro-hormonal influence over blood pressure. When kidneys fail a host of pathophysiological changes ensue resulting in both acute and chronic disease, which carry significant risk to patients and burden on healthcare resources. Acute kidney injury (AKI), chronic kidney disease (CKD) and acute-on-chronic kidney failure are increasingly common clinical entities, presenting significant challenges to the perioperative physician. The presence of renal disease is an independent risk factor for increased morbidity, mortality and length of hospital and intensive care stay. This article focuses on the clinical anaesthetic assessment of the renal patient prior to surgery.

Background Frailty is a state of vulnerability to poor resolution of homeostasis after a stressor event and is strongly associated with adverse outcomes. Therefore, the assessment of frailty may be an essential part of evaluation in any healthcare encounter that might result in an escalation of care. The purpose of the study was to assess the frequency and association of frailty with clinical outcomes in patients subject to rapid response team (RRT) review. Methods In this multi-national prospective observational cohort study, centres with existing RRTs collected data over a 7-day period, with follow up of all patients at 24 h following their RRT call and at hospital discharge or 30 days following the event trigger (whichever came sooner). Investigators also collected data on the triggers and interventions provided and a bedside assessment on the level of patients’ frailty using a clinical frailty scale. Results Amongst 1133 patients, 40% were screened as frail, which was associated with older age (p

Purpose: The purpose of the study is to understand what clinicians believe defines fluid bolus therapy (FBT) and the expected response to such intervention. Methods: We asked intensive care specialists in 30 countries to participate in an electronic questionnaire of their practice, definition, and expectations of FBT. Results: We obtained 3138 responses. Despite much variation, more than 80% of respondents felt that more than 250 mL of either colloid or crystalloid fluid given over less than 30 minutes defined FBT, with crystalloids most acceptable. The most acceptable crystalloid and colloid for use as FBT were 0.9% saline and 4% albumin solution, respectively. Most respondents believed that one or more of the following physiological changes indicates a response to FBT: a mean arterial pressure increase greater than 10 mm Hg, a heart rate decrease greater than 10 beats per minute, an increase in urinary output by more than 10 mL/h, an increase in central venous oxygen saturation greater than 4%, or a lactate decrease greater than 1 mmol/L. Conclusions: Despite wide variability between individuals and countries, clear majority views emerged to describe practice, define FBT, and identify a response to it. Further investigation is now required to describe actual FBT practice and to identify the magnitude and duration of the physiological response to FBT and its relationship to patient-centered outcomes., Facultad de Ciencias Médicas

The study was developed to characterize short-term outcomes of deteriorating ward patients triggering a Rapid Response Team (RRT), and describe variability between hospitals or groups thereof.We performed an international prospective study of Rapid Response Team (RRT) activity over a 7-day period in February 2014. Investigators at 51 acute hospitals across Australia, Denmark, the Netherlands, USA and United Kingdom collected data on all patients triggering RRT review concerning the nature, trigger and immediate outcome of RRT review. Further follow-up at 24h following RRT review focused on patient orientated outcomes including need for admission to critical care, change in limitations of therapy and all cause mortality.We studied 1188 RRT activations. Derangement of vital signs as measured by the National Early Warning Score (NEWS) was more common in non-UK hospitals (p=0.03). Twenty four hour mortality after RRT review was 10.1% (120/1188). Urgent transfer to ICU or the operating theatre occurred in 24% (284/1188) and 3% (40/1188) of events, respectively. Patients in the UK were less likely to be admitted to ICU (31% vs. 22%; p=0.017) and their median (IQR) time to ICU admission was longer [4.4 (2.0-11.8) vs. 1.5 (0.8-4.4)h; p0.001]. RRT involvement lead to new limitations in care in 28% of the patients not transferring to the ICU; in the UK such limitations were instituted in 21% of patients while this occurred in 40% of non-UK patients (p0.001).Among patients triggering RRT review, 1 in 10 died within 24h; 1 in 4 required ICU admission, and 1 in 4 had new limitations in therapy implemented. We provide a template for an international comparison of outcomes at RRT level.

There is widespread concern regarding excess mortality for patients admitted to hospital out of hours. We introduced an electronic track and trigger system (Patientrack) with automated alerts in a large university teaching hospital between 2010 and 2012. The system computes the patient's early warning score and alerts medical staff via a pager. It is operational 24 hours a day, 7 days a week and could be an effective tool to reduce variations in mortality throughout the working week.

We read with interest the systematic review by Karvellas and colleagues on early versus late renal replacement therapy (RRT) in critically ill patients with acute kidney injury (AKI) [1]. The authors rightly cite enormous heterogeneity between the 15 studies reviewed as a key concern. We would like to focus on the varied approach and lack of consensus in defining early and late initiation of RRT, as all of the 15 studies quote different definitions in their methods. Even those utilising similar markers and criteria for AKI - for example, the RIFLE criteria [2] (two studies) or blood urea and nitrogen (four studies) - utilised and interpreted them in very different ways when distinguishing early and late initiation of RRT. None of the studies reviewed used the Acute Kidney Injury Network (AKIN) criteria [3]. Having applied the AKIN criteria to data from our 20-bed critical care unit for all patients receiving RRT in 2009 (n = 158), we also failed to show RRT initiated at an early stage of AKI to be of benefit in terms of critical care or hospital survival. Figure ​Figure11 shows a higher rate of hospital mortality in patients with AKIN stage 1 AKI (P = 0.01). Patient characteristics including age, sex and Acute Physiology and Chronic Health Evaluation scores were similar across all groups. In view of our experience and Karvellas and colleagues' conclusions, surely the matter of greatest urgency prior to any multicentre trial is establishing a satisfactory definition for early and late initiation of RRT. Figure 1 Hospital survival based on acute kidney injury staging. Histogram for hospital survival based on acute kidney injury (AKI) staging according to Acute Kidney Injury Network criteria [3] (n = 143). RRT, renal replacement therapy.