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Over the past few years, chloride has joined the league of essential electrolytes for critically ill patients. Dyschloremia can occur secondary to various etiologic factors before and during patient admission in the intensive care unit. Some cases are disease-related; others, treatment-related. Chloride abnormalities were shown in animal models to have adverse effects on arterial blood pressure, renal blood flow, and inflammatory markers, which have led to several clinical investigations. Hyperchloremia was studied in several settings and correlated to different outcomes, including death and acute kidney injury. Baseline hypochloremia, to a much lesser extent, has been studied and associated with similar outcomes. The chloride content of resuscitation fluids was also a subject of clinical research. In this review, we describe the effect of dyschloremia on outcomes in critically ill patients. We review the major studies assessing the chloride content of resuscitation fluids in the critically ill patient.

Acute upper gastrointestinal haemorrhage due to peptic ulcer bleeding remains an important cause of emergency presentation and hospital admission. Despite advances in many aspects of management, peptic ulcer bleeding is still associated with significant morbidity, mortality, and healthcare costs. Comprehensive international guidelines have been published, but advances as well as controversies continue to evolve. Important recent advances include the evidence supporting a more restrictive transfusion strategy aiming for a target haemoglobin of 70–90 g/l. Comparative studies have confirmed that the Glasgow–Blatchford score remains the most useful score for predicting the need for intervention as well as for identifying the lowest-risk patients suitable for outpatient management. New scores, including the AIMS65 and Progetto Nazionale Emorragia Digestiva score, may be more accurate in predicting mortality. Pre-endoscopy erythromycin appears to improve outcomes and is probably underused. High-dose oral proton pump inhibition (PPI) for 11 days after PPI infusion is advantageous in those with a Rockall score of 6 or more. Oral is as effective as parenteral iron at restoring haemoglobin levels after a peptic ulcer bleed and both are superior to placebo in this respect. Within endoscopic techniques, haemostatic powders and over-the-scope clips can be used when other methods have failed. A disposable Doppler probe appears to provide more accurate determination of both rebleeding risk and the success of endoscopic therapy than purely visual guidance. Non- Helicobacter pylori, non-aspirin/non-steroidal anti-inflammatory drug ulcers contribute an increasing percentage of bleeding peptic ulcers and are associated with a poor prognosis and high rebleeding rate. The optimal management of these ulcers remains to be determined.

Although there have been advances made in the diagnosis and management of pediatric acute liver failure, there is still no consensus regarding the definition or standardized evaluation, and an inability to predict outcomes, specifically irreversible brain injury, in many patients exists. Much of the research surrounding pediatric acute liver failure in the last several years has centered on the development of predictive scoring systems to enhance diagnosis and treatment decisions. In this article, we will discuss our current understanding of liver failure and updated management strategies in children with acute liver failure.

Acute Kidney Injury (AKI), an abrupt deterioration in kidney function, is defined by changes in urine output or serum creatinine. AKI is common (affecting up to 20% of acute hospital admissions in the United Kingdom), associated with significant morbidity and mortality, and expensive (excess costs to the National Health Service in England alone may exceed £1 billion per year). NHS England has mandated the implementation of an automated algorithm to detect AKI based on changes in serum creatinine, and to alert clinicians. It is uncertain, however, whether ‘alerting’ alone improves care quality. We have thus developed a digitally-enabled care pathway as a clinical service to inpatients in the Royal Free Hospital (RFH), a large London hospital. This pathway incorporates a mobile software application - the “Streams-AKI” app, developed by DeepMind Health - that applies the NHS AKI algorithm to routinely collected serum creatinine data in hospital inpatients. Streams-AKI alerts clinicians to potential AKI cases, furnishing them with a trend view of kidney function alongside other relevant data, in real-time, on a mobile device. A clinical response team comprising nephrologists and critical care nurses responds to these AKI alerts by reviewing individual patients and administering interventions according to existing clinical practice guidelines. We propose a mixed methods service evaluation of the implementation of this care pathway. This evaluation will assess how the care pathway meets the health and care needs of service users (RFH inpatients), in terms of clinical outcome, processes of care, and NHS costs. It will also seek to assess acceptance of the pathway by members of the response team and wider hospital community. All analyses will be undertaken by the service evaluation team from UCL (Department of Applied Health Research) and St George’s, University of London (Population Health Research Institute).

Acute Kidney Injury (AKI), an abrupt deterioration in kidney function, is defined by changes in urine output or serum creatinine. AKI is common (affecting up to 20% of acute hospital admissions in the United Kingdom), associated with significant morbidity and mortality, and expensive (excess costs to the National Health Service in England alone may exceed £1 billion per year). NHS England has mandated the implementation of an automated algorithm to detect AKI based on changes in serum creatinine, and to alert clinicians. It is uncertain, however, whether ‘alerting’ alone improves care quality. We have thus developed a digitally-enabled care pathway as a clinical service to inpatients in the Royal Free Hospital (RFH), a large London hospital. This pathway incorporates a mobile software application - the “Streams-AKI” app, developed by DeepMind Health - that applies the NHS AKI algorithm to routinely collected serum creatinine data in hospital inpatients. Streams-AKI alerts clinicians to potential AKI cases, furnishing them with a trend view of kidney function alongside other relevant data, in real-time, on a mobile device. A clinical response team comprising nephrologists and critical care nurses responds to these AKI alerts by reviewing individual patients and administering interventions according to existing clinical practice guidelines. We propose a mixed methods service evaluation of the implementation of this care pathway. This evaluation will assess how the care pathway meets the health and care needs of service users (RFH inpatients), in terms of clinical outcome, processes of care, and NHS costs. It will also seek to assess acceptance of the pathway by members of the response team and wider hospital community. All analyses will be undertaken by the service evaluation team from UCL (Department of Applied Health Research) and St George’s, University of London (Population Health Research Institute).

Perioperative myocardial ischemia and infarction are the leading causes of morbidity and mortality following anesthesia and surgery. The discovery of endogenous cardioprotective mechanisms has led to testing of new methods to protect the human heart. These approaches have included ischemic pre-conditioning, per-conditioning, post-conditioning, and remote conditioning of the myocardium. Pre-conditioning and per-conditioning include brief and repetitive periods of sub-lethal ischemia before and during prolonged ischemia, respectively; and post-conditioning is applied at the onset of reperfusion. Remote ischemic conditioning involves transient, repetitive, non-lethal ischemia and reperfusion in one organ or tissue (remote from the heart) that renders myocardium more resistant to lethal ischemia/reperfusion injury. In healthy, young hearts, many conditioning maneuvers can significantly increase the resistance of the heart against ischemia/reperfusion injury. The large multicenter clinical trials with ischemic remote conditioning have not been proven successful in cardiac surgery thus far. The lack of clinical success is due to underlying risk factors that interfere with remote ischemic conditioning and the use of cardioprotective agents that have activated the endogenous cardioprotective mechanisms prior to remote ischemic conditioning. Future preclinical research using remote ischemic conditioning will need to be conducted using comorbid models.

Nephrotoxic medication exposure is nearly ubiquitous in hospitalized patients and represents one of the most common causes of acute kidney injury (AKI) in the hospitalized setting. Although provision of medications that are nephrotoxic has led to improved outcomes in terms of treatment of underlying illness, unnecessary nephrotoxic medication exposure can be viewed as a potentially modifiable adverse safety event if AKI can be prevented. The advancements in electronic health record development, standardization of AKI definitions, and the ability to identify AKI risk and development in near real time provide opportunities to reduce harm from nephrotoxicity.

Critically ill patients are often hemodynamically unstable (or at risk of becoming unstable) owing to hypovolemia, cardiac dysfunction, or alterations of vasomotor function, leading to organ dysfunction, deterioration into multi-organ failure, and eventually death. With hemodynamic monitoring, we aim to guide our medical management so as to prevent or treat organ failure and improve the outcomes of our patients. Therapeutic measures may include fluid resuscitation, vasopressors, or inotropic agents. Both resuscitation and de-resuscitation phases can be guided using hemodynamic monitoring. This monitoring itself includes several different techniques, each with its own advantages and disadvantages, and may range from invasive to less- and even non-invasive techniques, calibrated or non-calibrated. This article will discuss the indications and basics of monitoring, further elaborating on the different techniques of monitoring.

An evaluation of a recent study by Niemann CU, Feiner J, Swain S et al. Therapeutic Hypothermia in Deceased Organ Donors and Kidney-Graft Function. New England Journal of Medicine 2015; 373 (5):405-414. PubMed PMID: 26222557. ClinicalTrials.gov number, NCT01680744

Acute kidney injury is strongly associated with increased mortality and other adverse outcomes. Medical researchers have intensively investigated novel biomarkers to predict short- and long-term outcomes of acute kidney injury in many patient care settings, such as cardiac surgery, intensive care units, heart failure, and transplant. Future research should focus on leveraging this relationship to improve enrollment for clinical trials of acute kidney injury.

Acute kidney injury (AKI) is one of the most relevant complications after major surgery and is a predictor of mortality. In Western countries, patients at risk of developing AKI are mainly those undergoing cardiovascular surgical procedures. In this category of patients, AKI depends on a multifactorial etiology, including low ejection fraction, use of contrast media, hemodynamic instability, cardiopulmonary bypass, and bleeding. Despite a growing body of literature, the treatment of renal failure remains mainly supportive (e.g. hemodynamic stability, fluid management, and avoidance of further damage); therefore, the management of patients at risk of AKI should aim at prevention of renal damage. Thus, the present narrative review analyzes the pathophysiology underlying AKI (specifically in high-risk patients), the preoperative risk factors that predispose to renal damage, early biomarkers related to AKI, and the strategies employed for perioperative renal protection. The most recent scientific evidence has been considered, and whenever conflicting data were encountered possible suggestions are provided.

During the last few years, due to medical and surgical evolution, patients with increasingly severe diseases causing multiorgan dysfunction are frequently admitted to intensive care units. Therapeutic options, when organ failure occurs, are frequently nonspecific and mostly directed towards supporting vital function. In these scenarios, the kidneys are almost always involved and, therefore, renal replacement therapies have become a common routine practice in critically ill patients with acute kidney injury. Recent technological improvement has led to the production of safe, versatile and efficient dialysis machines. In addition, emerging evidence may allow better individualization of treatment with tailored prescription depending on the patients’ clinical picture (e.g. sepsis, fluid overload, pediatric). The aim of the present review is to give a general overview of current practice in renal replacement therapies for critically ill patients. The main clinical aspects, including dose prescription, modality of dialysis delivery, anticoagulation strategies and timing will be addressed. In addition, some technical issues on physical principles governing blood purification, filters characteristics, and vascular access, will be covered. Finally, a section on current standard nomenclature of renal replacement therapy is devoted to clarify the “Tower of Babel” of critical care nephrology.

A common indication for laparoscopic mesenteric lymph node biopsy is to provide a tissue diagnosis in the absence of palpable peripheral nodes via a minimally invasive approach. There are no reports to date of ischaemia to the appendix as a complication of this procedure. We report the case of a 34-year-old lady who underwent a mesenteric biopsy for a lesion found incidentally on CT to investigate longstanding abdominal pain, and 2 days later required an appendicectomy for ischaemic appendicitis.

This article will review the recent advances in managing acute pancreatitis. Supportive care has long been the standard of treatment for this disease despite extensive, but ultimately unsuccessful, efforts to develop disease-specific pharmacologic therapies. The primary interventions center on aggressive fluid resuscitation, initiation of early enteral nutrition, targeted antibiotic therapy, and the management of complications. In this article, we will detail treatment of acute pancreatitis with a focus on intravenous fluid resuscitation, enteral feeding, and the current evidence behind the use of antibiotics and other pharmacologic therapies.

Necrotizing enterocolitis is a devastating intestinal disease that affects ~5% of preterm neonates. Despite advancements in neonatal care, mortality remains high (30–50%) and controversy still persists with regards to the most appropriate management of neonates with necrotizing enterocolitis. Herein, we review some controversial aspects regarding the epidemiology, imaging, medical and surgical management of necrotizing enterocolitis and we describe new emerging strategies for prevention and treatment.

An evaluation of a recent study by MacLaren R, Reynolds PM, Allen RR et al: Histamine-2 receptor antagonists vs proton pump inhibitors on gastrointestinal tract hemorrhage and infectious complications in the intensive care unit. JAMA Intern Med 2014, 174:564-574.

Introduction: The aim of this study was to assess the outcomes of early vascular release in robot-assisted laparoscopic partial nephrectomy (RAPN) to reduce warm ischaemia time (WIT) and minimise renal dysfunction. RAPN is increasingly utilised in the management of small renal masses. To this end it is imperative that WIT is kept to a minimum to maintain renal function. Methods: RAPN was performed via a four-arm robotic transperitoneal approach. The renal artery and vein were individually clamped with robotic vascular bulldog clamps to allow cold scissor excision of the tumour. The cut surface was then sutured with one or two running 3-0 V-Loc TM sutures, following which the vascular clamps were released. Specific bleeding vessels were then selectively oversewn and the collecting system repaired. Renorrhaphy was then completed using a running horizontal mattress 0-0 V-Loc TM suture. Results: A total of 16 patients underwent RAPN with a median WIT of 15 minutes (range: 8-25), operative time 230 minutes (range: 180-280) and blood loss of 100 mL (range: 50-1000). There were no transfusions, secondary haemorrhages or urine leaks. There was one focal positive margin in a central 5.5 cm pT3a renal cell carcinomas (RCC). Long-term estimated glomerular filtration rate (eGFR) was not significantly different to pre-operative values. Conclusion: In this patient series, early vascular release effectively minimised WIT and maintained renal function without compromising perioperative safety.

Introduction: The aim of this study was to assess the outcomes of early vascular release in robot-assisted laparoscopic partial nephrectomy (RAPN) to reduce warm ischaemia time (WIT) and minimise renal dysfunction. RAPN is increasingly utilised in the management of small renal masses. To this end it is imperative that WIT is kept to a minimum to maintain renal function. Methods: RAPN was performed via a four-arm robotic transperitoneal approach. The renal artery and vein were individually clamped with robotic vascular bulldog clamps to allow cold scissor excision of the tumour. The cut surface was then sutured with one or two running 3-0 V-LocTM sutures, following which the vascular clamps were released. Specific bleeding vessels were then selectively oversewn and the collecting system repaired. Renorrhaphy was then completed using a running horizontal mattress 0-0 V-LocTM suture. Results: A total of 16 patients underwent RAPN with a median WIT of 15 minutes (range: 8-25), operative time 230 minutes (range: 180-280) and blood loss of 100 mL (range: 50-1000). There were no transfusions, secondary haemorrhages or urine leaks. There was one focal positive margin in a central 5.5 cm pT3a renal cell carcinomas (RCC). Long-term estimated glomerular filtration rate (eGFR) was not significantly different to pre-operative values. Conclusion: In this patient series, early vascular release effectively minimised WIT and maintained renal function without compromising perioperative safety.

We have utilized the persistent elevation of fractional excretion (FE) of urate, > 10%, to differentiate cerebral/renal salt wasting (RSW) from the syndrome of inappropriate antidiuretic hormone secretion (SIADH), in which a normalization of FEurate occurs after correction of hyponatremia. Previous studies suggest as well that an elevated FEurate with normonatremia, without pre-existing hyponatremia, is also consistent with RSW, including studies demonstrating induction of RSW in rats infused with plasma from normonatremic neurosurgical and Alzheimer’s disease patients. The present studies were designed to test whether precipitates from the urine of normonatremic neurosurgical patients, with either normal or elevated FEurate, and patients with SIADH, display natriuretic activity. Methods: Ammonium sulfate precipitates from the urine of 6 RSW and 5 non-RSW Control patients were dialyzed (10 kDa cutoff) to remove the ammonium sulfate, lyophilized, and the reconstituted precipitate was tested for its effect on transcellular transport of 22Na across LLC-PK1 cells grown to confluency in transwells. Results: Precipitates from 5 of the 6 patients with elevated FEurate and normonatremia significantly inhibited the in vitro transcellular transport of 22Na above a concentration of 3 μg protein/ml, by 10-25%, versus to vehicle alone, and by 15-40% at concentrations of 5-20 μg/ml as compared to precipitates from 4 of the 5 non-RSW patients with either normal FEurate and normonatremia (2 patients) or with SIADH (2 patients). Conclusion: These studies provide further evidence that an elevated FEurate with normonatremia is highly consistent with RSW. Evidence in the urine of natriuretic activity suggests significant renal excretion of the natriuretic factor. The potentially large source of the natriuretic factor that this could afford, coupled with small analytical sample sizes required by the in-vitro bioassay used here, should facilitate future experimental analysis and allow the natriuretic factor to be investigated as a potential biomarker for RSW.

We have utilized the persistent elevation of fractional excretion (FE) of urate, > 10%, to differentiate cerebral/renal salt wasting (RSW) from the syndrome of inappropriate antidiuretic hormone secretion (SIADH), in which a normalization of FEurate occurs after correction of hyponatremia. Previous studies suggest as well that an elevated FEurate with normonatremia, without pre-existing hyponatremia, is also consistent with RSW, including studies demonstrating induction of RSW in rats infused with plasma from normonatremic neurosurgical and Alzheimer’s disease patients. The present studies were designed to test whether precipitates from the urine of normonatremic neurosurgical patients, with either normal or elevated FEurate, and patients with SIADH, display natriuretic activity. Methods: Ammonium sulfate precipitates from the urine of 6 RSW and 5 non-RSW Control patients were dialyzed (10 kDa cutoff) to remove the ammonium sulfate, lyophilized, and the reconstituted precipitate was tested for its effect on transcellular transport of 22Na across LLC-PK1 cells grown to confluency in transwells. Results: Precipitates from 5 of the 6 patients with elevated FEurate and normonatremia significantly inhibited the in vitro transcellular transport of 22Na above a concentration of 3 μg protein/ml, by 10-25%, versus to vehicle alone, and by 15-40% at concentrations of 5-20 μg/ml as compared to precipitates from 4 of the 5 non-RSW patients with either normal FEurate and normonatremia (2 patients) or with SIADH (2 patients). Conclusion: These studies provide further evidence that an elevated FEurate with normonatremia is highly consistent with RSW. Evidence in the urine of natriuretic activity suggests significant renal excretion of the natriuretic factor. The potentially large source of the natriuretic factor that this could afford, coupled with small analytical sample sizes required by the in-vitro bioassay used here, should facilitate future experimental analysis and allow the natriuretic factor to be investigated as a potential biomarker for RSW.

Transcatheter aortic valve replacement (TAVR) is rapidly gaining popularity as a technique to surgically manage aortic stenosis (AS) in high risk patients. TAVR is significantly less invasive than the traditional approach to aortic valve replacement via median sternotomy. Patients undergoing TAVR often suffer from multiple comorbidities, and their postoperative course may be complicated by a unique set of complications that may become evident in the intensive care unit (ICU). In this article, we review the common complications of TAVR that may be observed in the ICU, and different strategies for their management.

We have utilized the persistent elevation of fractional excretion (FE) of urate, > 10%, to differentiate cerebral/renal salt wasting (RSW) from the syndrome of inappropriate antidiuretic hormone secretion (SIADH), in which a normalization of FEurate occurs after correction of hyponatremia. Previous studies suggest as well that an elevated FEurate with normonatremia, without pre-existing hyponatremia, is also consistent with RSW, including studies demonstrating induction of RSW in rats infused with plasma from normonatremic neurosurgical and Alzheimer’s disease patients. The present studies were designed to test whether precipitates from the urine of normonatremic neurosurgical patients, with either normal or elevated FEurate, and patients with SIADH, display natriuretic activity. Methods: Ammonium sulfate precipitates from the urine of 6 RSW and 5 non-RSW Control patients were dialyzed (10 kDa cutoff) to remove the ammonium sulfate, lyophilized, and the reconstituted precipitate was tested for its effect on transcellular transport of 22Na across LLC-PK1 cells grown to confluency in transwells. Results: Precipitates from 5 of the 6 patients with elevated FEurate and normonatremia significantly inhibited the in vitro transcellular transport of 22Na above a concentration of 3 μg protein/ml, by 10-25%, versus to vehicle alone, and by 15-40% at concentrations of 5-20 μg/ml as compared to precipitates from 4 of the 5 non-RSW patients with either normal FEurate and normonatremia (2 patients) or with SIADH (2 patients). Conclusion: These studies provide further evidence that an elevated FEurate with normonatremia is highly consistent with RSW. Evidence in the urine of natriuretic activity suggests significant renal excretion of the natriuretic factor. The potentially large source of the natriuretic factor that this could afford, coupled with small analytical sample sizes required by the in-vitro bioassay used here, should facilitate future experimental analysis and allow the natriuretic factor to be investigated as a potential biomarker for RSW.

Transcatheter aortic valve replacement (TAVR) is rapidly gaining popularity as a technique to surgically manage aortic stenosis (AS) in high risk patients. TAVR is significantly less invasive than the traditional approach to aortic valve replacement via median sternotomy. Patients undergoing TAVR often suffer from multiple comorbidities, and their postoperative course may be complicated by a unique set of complications that may become evident in the intensive care unit (ICU). In this article, we review the common complications of TAVR that may be observed in the ICU, and different strategies for their management.