Neuro Resus

According to a quote variably attributed to Niels Bohr, Yogi Berra, Albert Einstein, Mark Twain and others 'prediction is difficult; especially about the future'. Nevertheless, in an era of evidence-based medicine, one might surmise that the future of management of GI bleeding in the ICU will be informed by large-scale high quality RCTs. There are a number of such trials on the horizon that give us a pretty good idea of what the future holds. Based on my best-guess of what these trials will show I predict that in the future we will: 1. Use more TXA in patients with GI bleeding. 2. Use less stress ulcer prophylaxis. The Haemorrhage ALleviation with Tranexamic acid (TXA) – InTestinal system trial (HALT-IT) is a pragmatic trial that will compare TXA to placebo in 8000 participants with clinically significant gastrointestinal bleeding. The rationale for this trial is that decreasing fibrinolysis with TXA will increase clot stability, improve haemostasis, and reduce rebleeding, leading to reduced mortality for patients presenting with GI bleeds. Additional information about the role of TXA will come from a second trial, the EXARHOSE trial, which will investigate the safety and efficacy of TXA in cirrhotic patients with acute upper GI bleeding. There are two large-scale RCTs comparing proton pump inhibitors to placebo coming soon. The first is the SUP-ICU trial, which is being run by the Scandinavian Critical Care Trials Group. This trial will enrol adult patients with one or more risk factors for upper GI bleeding and has a primary end point of day 90 mortality. The second is the REVISE trial which includes patients who are mechanically ventilated in ICU and expected to be ventilated the day after tomorrow. REVISE has a primary end point of 'clinically significant GI bleeding'. Together SUP-ICU and REVISE have a combined sample size of over 8000 participants and will help us to better understand the effects of PPI use on mortality risk, GI bleeding risk, VAP risk, and C. diff infection risk. The results of these trials will be complemented by the PIC-UP trial which will investigate the role of stress ulcer prophylaxis in PICU patients and the PEPTIC trial which compares PPIs and H2RBs in mechanically ventilated adults.

Peptic ulcer bleeding (PUB) carries a 10% risk of death within 30 days and accounts for 36–46% of emergency upper gastrointestinal bleedings (UGIBs). The annual incidence of hospitalization due to PUB is 19–57 per 100,000 persons. Most of these patients undergo esophago-gastro-duodenoscopy (EGD), estimated to 2000 patients in Denmark alone every year. The poor prognosis in PUB is partly due to the clinical condition itself, and partly due to the high prevalence of medical comorbidities. Hence, optimizing pre-, intra-, and post-endoscopic patient management are likely to be important in order to minimize the risk of death and improve outcome. Although duodenal ulcer (DU) and gastric ulcer (GU) seem to be identical diseases with a considerable overlap in both risk-factor profile and clinical manifestations, ulcer site could potentially affect outcome. However, the prognostic importance of ulcer site has not been extensively evaluated, and existing knowledge is ambiguous. Two systematic reviews of predictors of re-bleeding after endoscopic treatment reported that posterior DUs and ulcers on the lesser gastric curvature more often were associated with haemostatic failure. A recent cohort study reported that bleeding DU was associated with poorer outcome than bleeding GU in terms of mortality, need for surgery and readmission. However, another large cohort from Hong Kong did not find that DU site was associated with increased mortality. Limited data exist on the prognostic importance of ulcer site in patients with PPU. In a nationwide cohort study comprising more than 24,000 Danish patients with complicated PUD, a significantly higher 30- and 90-d all-cause mortality rates were found, and more re-interventions in patients with bleeding DU compared with patients with bleeding GU, suggesting that ulcer site is an important predictor for poor outcome in patients with PUB. In patients with PPU, no significant association was seen between ulcer site and mortality or re-intervention. Finally, the proportion of GU increased slightly over time. Critically ill patients in the intensive care unit (ICU) are at risk of clinically important gastrointestinal bleeding, and acid suppressants are frequently used prophylactically. However, stress ulcer prophylaxis may increase the risk of serious adverse events and, additionally, the quantity and quality of evidence supporting the use of stress ulcer prophylaxis is low. The aims of some recent trial have been to assess the benefits and harms of stress ulcer prophylaxis with a proton pump inhibitor in adult patients in the ICU. It has been hypothesized that stress ulcer prophylaxis reduces the rate of gastrointestinal bleeding, but increases rates of nosocomial infections and myocardial ischaemia. The overall effect on mortality seems to be unpredictable.

At this year's CICM ASM in Hobart, Tasmania, there will be the second CICM trainee symposium. This is a day of lectures and discussions targeted specifically at CICM ICU trainees and immediately precedes the CICM ASM meeting itself. More details are here.

Acute liver failure - what tomorrow might bring? by Professor Julia Wendon

Because of widespread recognition that surgical quality varies widely, there is growing demand from patients, providers, and payers for better measures of surgical outcomes. Risk-adjusted mortality rates are a simple and reliable measure of surgical quality and have been used to good effect in cardiac surgery. One way to improve outcomes measurement in non-cardiac surgery is to combine several operations together when assessing hospital mortality rates. While previous studies show relatively weak relationships between outcomes for different medical diagnoses, there is some reason to believe these relationships may be stronger in surgery. Many high-risk operations are dependent on the same hospital-level resources, staffing, and processes of care. Findings suggest that procedure-specific mortality is strongly related to a hospital's mortality with other operations. In some cases, mortality with other operations is a better predictor than other proxy measures of quality, including hospital volume. The main result, that hospitals good at one operation tend to be good at others, has important implications for measuring the quality of non-cardiac surgery. Structural characteristics important to all high-risk operations include intensivist staffing of critical care units, high nurse to patient ratios, and the presence of high-volume, specialty trained surgeons.

They also depend on many of the same processes of care. Shared processes of care related to patient outcomes include preoperative cardiac evaluation, appropriate use of perioperative antibiotics, beta blockers, and venous thromboembolism prophylaxis, and postoperative pain management. Three specific major GI surgical procedures will be discussed. Still the primary method of treating patients with esophageal cancer has been surgery. However, the traditional open esophagectomy (OE) procedure has high complication rates resulting in significant morbidity and mortality. Various studies showed in-hospital mortality between 1.2 and 8.8% , even as high as 29%. Minimally invasive oesophagectomy (MIO), which was first described in the 1990s, was attributed to be superior in reducing postoperative outcomes, without compromising oncological outcomes and avoiding thoracotomy and laparotomy. The basis of minimally invasive techniques in esophageal surgery is to maintain the therapy effectiveness and quality of traditional operations, while reducing perioperative injury. Nevertheless, the real benefits of minimally invasive approach for esophagectomy are still controversial. A number of meta-analyses and even randomized controlled trials demonstrated MIO to be superior in reducing risk of postoperative outcomes, but their results are not very consistent, especially on the issue of in-hospital mortality

The second is major hepatectomy which is increasingly used in patients with colorectal liver metastases (CRCLM) and cholangiocarcinoma and the recent figures for postoperative morbidity and mortality suggest wide safety margins. The limits of resection are, however, continuously tested and extended hepatectomy is used to remove larger and larger proportions of liver parenchyma.

In a patient with a normal liver, a small future liver remnant [FLR] may be enough to support a normal functional recovery, whereas in a patient with a diseased liver (e.g., a cirrhotic liver or liver damaged by very extensive chemotherapy), a larger FLR is presumably mandatory to ensure adequate postoperative liver function. Certainly volume and liver disease are not the only determinates of outcome, but careful assessment of liver volume can be used as an accurate measure to reduce the risk of life threatening complications, liver failure and death after major hepatectomies. Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has rendered great attention since its introduction. Although showing promising results with unprecedented growth of FLR, both in time and size, the technique has also been subjected to criticism, mainly because of high morbidity and mortality rates. A recent review of the literature shows that the majority of the serious complications affect patients subjected to concomitant biliary surgery, while patients with colorectal liver metastases (CRLM) undergoing ALPPS seem to be less prone to develop high-grade complications.

Finally many studies have shown that resection of pancreatic tumor with venous resection have equal morbidity/mortality compared to when no venous resection is done, at least in experienced hands. The case for arterial reconstructions is not that unanimous but several authors have shown case series that this is a feasible option for longer survival in the right patient, as long as the margin is clear of tumor involvement. The prognosis is worse compared to resections without the necessity to reconstruct the SMA, the celiac trunk or hepatic artery. There is also heterogeneity in the literature regarding the definition of borderline resectability and locally advanced (incurable) pancreatic cancer. Another aspect is that former CT generations seem to slightly overestimate vascular involvement of the tumor but remain accurate regarding the retroperitoneal fat tissue infiltration.

That the gastrointestinal tract exerts an important, but unseen role in the pathogenesis of human disease has been a recurring theme over recorded human history. The Egyptians believed that a factor from the gut known as "ukhedu", or "something disgusting", was a factor in disease. At the turn of the century, and based on the ideas of Elie Metchnikoff, the gut was held responsible for the process of aging, and multiple innovative approaches were tried to arrest the passage of time. Following World War II, the gut was proposed to contain a factor (later shown to be endotoxin) that contributed to the hemodynamic arrangements of shock, and 30 years ago, we and others proposed that the gut was the motor of multiple organ failure. Today the focus of studies of the gut in critical illness is on the microbiome, and the way in which illness alters it. Each of these paradigms has generated new pathologic and therapeutic insights. The human GI tract contains a remarkable number and diversity of microorganisms in intimate proximity to a complex immune network in the gut wall, the liver, and the spleen. It also contains 25 grams of endotoxin – enough to kill 6 million people. Acute critical illness results in striking changes in this flora, reducing the diversity, and increasing the concentrations of many of the species that predominate in ICU-acquired infections. These organisms can invade normally sterile tissues through aspiration or translocation across an intact gut wall. The flora can be altered not only in its composition, but also in the inherent virulence of its constituents, changes that are induced by interactions with the local intestinal environment. A normal flora is essential to the normal development and maturation of the metabolic and immunologic function of the gut. Conversely, an altered flora can contribute to systemic alterations in immune responsiveness, perhaps through interactions with Kupffer cells in the liver. Moreover endotoxin from Gram-negative bacteria can be absorbed following trauma or other states associated with altered splanchnic perfusion. The spectrum of interventions based on a knowledge of the role of the gut in critical illness is broad. Simple interventions such as early feeding to maintain mucosal integrity are widely used. The impact of other gut-directed measures such as stress ulcer prophylaxis is undergoing re-evaluation. Selective digestive tract decontamination (SDD) has been shown to reduce both rates of nosocomial infection and mortality following ICU admission, but is not widely used for reasons that are not entirely clear. The converse approach – selective colonization either with probiotics or even fecal transplants – is also showing evidence of clinical efficacy. The gut is one of the most complex, yet one of the most elusive organs of the body. As the locus of the most important interactions between the human and microbial worlds, it remains a source of continuing discovery in critical illness.

Resilience and Sustainable Work Practices by Dr Bronwyn Avard

Landing a consultant job, requires a different mind set than any job interview you have had prior. As well as your brand new, hard won, consultoid clinical skills, you will now have to interact with HR and Administration. This talk addresses tricks and tips for the interview process. Hints on what to say, and more importantly ...what not to say..

Clearing the C-Spine

The top 10 trials of the recent past are an interesting bunch highlighting some of the best and worst of evidence-based medicine. While they might not be all you need to know, they are some of what you need to know. Some are practice changing, some introduce new treatment paradigms that may change the way we practice in the near future. Sepsis trials, oxygen therapy in various forms, miracle cures, delirium-o-lysis, levosimendan, angiotensin-II, tranexamic acid, and decompressive craniectomy all feature. Anyone who doesn't think that the literature is interesting is bonkers.