bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnosis and management of variceal bleeding in the critically ill
Authors: Blisard Deanna , Al-Khafaji Ali
Published: April 2016

Cirrhosis is the most common cause of portal hypertension, which subsequently leads to development of gastroesophageal varices (GEV). Generally, presence of GEV correlates with the severity of cirrhosis and variceal haemorrhage can develop when hepatic venous pressure gradient exceeds 10–12 mmHg. The gold standard for diagnosis and often treatment of GEV is oesophagogastroduodenoscopy (OGD). Management of GEV is divided into primary prophylaxis, acute haemorrhage control, and secondary prophylaxis. Primary prophylaxis includes surveillance OGD and endoscopic intervention based on the size of the varices. Management of acute variceal haemorrhage includes resuscitation and endoscopic interventions. Basic resuscitative measures to maintain haemodynamic stability, vasoconstricting agents to decrease portal pressure, and the use of prophylactic antibiotics. Endoscopic intervention includes any of variceal band ligation, variceal sclerotherapy, and variceal obturation. Radiological or surgical portosystemic shunting markedly reduces portal pressure and are clinically effective therapy for patients who fail endoscopic or pharmacological therapy. Balloon tamponade is effective in temporarily controlling oesophageal variceal haemorrhage in over 80% of patients. Its use should be restricted to patients with uncontrollable bleeding, where more definitive therapy is planned within 24 hours. Secondary prophylaxis includes endoscopy plus pharmacological therapy of non-selective β‎−blockers.
Vomiting and large nasogastric aspirates in the critically ill
Authors: Gan Tong J. , Lemm John T.
Published: April 2016

A wide range of conditions can cause nausea and vomiting, making it a common occurrence in the critically ill. A deeper understanding of the pathophysiology of vomiting has led to the emergence of effective anti-emetics, each targeting a specific neurotransmitter in the emetic pathway. Serotonin antagonists are the first line anti-emetic of choice for most cases of nausea and vomiting due to their efficacy and favourable side effect profile. Large nasogastric aspirates are commonly encountered in the critically ill, and must be managed aggressively in order to prevent delays in enteral nutrition. Management of large gastric aspirates involves gastric drainage, prokinetic agents, and if necessary, post-pyloric feeding.
Ischaemic bowel in the critically ill
Authors: Peppelenbosch A. G. , Poeze Martijn
Published: April 2016

Intestinal ischaemia is caused by occlusion of the visceral arteries, thrombosis of the mesenteric veins, or by (low-flow) non-occlusive mesenteric ischaemia (NOMI). Each condition has a specific diagnostic and therapeutic work-up and prognostic significance. The incidence of acute mesenteric infarction is as low as 0.63 cases/100,000 person years, but overall mortality rates remains high at 74%. In general, a high index of suspicion is necessary and should be followed by administering therapeutic low molecular weight heparin or systemic heparin infusion. In these patients resuscitation and organ support are essential, but should not delay diagnostic work-up, including CT-angiography. With arterial occlusion, revascularization should be performed if indicated, preferentially using endovascular techniques prior to laparotomy. For venous occlusion, thrombolytic therapy directly into the superior mesenteric artery or venous thrombectomy can be performed, followed by laparotomy. The treatment of NOMI is to treat the underlying cause.
Acute acalculous cholecystitis in the critically ill
Authors: Ho Vanessa P. , Barie Philip S.
Published: April 2016

Acute acalculous cholecystitis (AAC) may occur in surgical or injured, critically-ill, and systemically-ill patients, with diabetes mellitus, malignant disease, abdominal vasculitis, congestive heart failure, cholesterol embolization, shock, and cardiac arrest. Children may also be affected, especially following a viral illness. The pathogenesis of AAC is complex and multifactorial. Ischaemia/reperfusion injury and the associated pro-inflammatory response and oxidative tissue stress, appear to be the central mechanisms, but bile stasis, opioid therapy, positive-pressure ventilation, and parenteral nutrition may all contribute to development of the disease. Ultrasound of the gallbladder is most accurate for the diagnosis of AAC in the critically-ill patient. Computed tomography is probably of comparable accuracy, but carries both advantages and disadvantages. Percutaneous cholecystostomy is now the treatment of choice, controlling AAC in about 85% of patients, despite the known high prevalence of gallbladder infarction (~50%) and perforation (~10%). Rapid improvement may be expected when AAC is diagnosed correctly and cholecystostomy is performed timely. The mortality (historically ~30%) of percutaneous and open cholecystostomy are similar, reflecting the severity of illness, but improved resuscitation and critical care may portend a decreased risk of death.
Pathophysiology and causes of jaundice in the critically ill
Authors: Padmakumar Anand D. , Bellamy Mark C.
Published: April 2016

Critically-ill patients develop jaundice for a variety of reasons. A good understanding of bilirubin metabolism can help the clinician to diagnose and treat jaundice. Intensive care unit (ICU) physicians commonly encounter elevated serum bilirubin in severely-ill patients, which can be associated with increased morbidity and mortality. A complex interaction of enzymatic pathways leads to safe excretion of bilirubin. This fine homeostasis is often disturbed and leads jaundice, which can be broadly classified into three main categories—prehepatic, hepatic, and post-hepatic. Common examples include sepsis, cardiac failure, drug toxicity, hepatic ischaemia, gall stone disease, etc. Management strategies directed towards the underlying causes aim to improve outcome. The aetiology can be often multifactorial and difficult to treat. This chapter provides a brief overview of bilirubin metabolism and aetiopathogenesis of jaundice. We also provide key recommendations to develop a systematic diagnostic approach, provide guidance on ordering appropriate investigations and on interpreting their results.
Management of jaundice in the critically ill
Authors: Padmakumar Anand D. , Bellamy Mark C.
Published: April 2016

There are many challenges that face intensivists identifying causes of jaundice in intensive care unit (ICU) patients. There is often an inevitable delay in correctly recognizing the aetiology, which can impact on initiating therapy. Despite appropriate institution of therapy in the form of fluids, vasoactive agents, mechanical ventilation, and nutrition, there is a possibility of inadvertently worsening hepatic injury due to various pathophysiological mechanisms discussed previously. This chapter aims to provide principles of management of the acutely-jaundiced ICU patient, focusing upon strategies to prevent hepatic injury, then reviewing therapeutic strategies for the management of liver injury per se. Specific treatment strategies are matched to aetiological categories. Definitive management should not delay initial resuscitation measures that can prevent secondary injury to vital organs. Some novel therapies are also discussed that might play a key role in future patient management.
Pathophysiology and causes of acute hepatic failure
Authors: Patel Sameer , Wendon Julia
Published: April 2016

Acute liver failure (ALF) is a rare, life-threatening clinical syndrome, resulting in loss of hepatic metabolic and immunological function, in a person with no prior history of liver disease. Mortality can still exceed 50%. ALF is characterized by hepatic encephalopathy (HE) and coagulopathy, occurring within days or weeks. Establishing aetiology is essential for treatment, prognostication, and liver transplantation consideration. Viral hepatitis and drug-induced liver failure are the two commonest causes worldwide. Aetiology and time of onset of encephalopathy determines prognosis. Disease progression can rapidly result in multi-organ failure. Ammonia has been postulated in the development of HE, cerebral oedema and intracranial hypertension. Coagulopathy can be highly variable, with some patients prothrombotic, or exhibiting balanced coagulation disorders. Systemic inflammatory response syndrome (SIRS) and associated infection are frequently observed. Significant haemodynamic changes are common while renal failure is an independent risk factor for mortality. Respiratory failure is less common. Deranged homeostasis results in severe hypoglycaemia, and metabolic disturbance.
The effect of acute hepatic failure on drug handling in the critically ill
Authors: Kortgen Andreas , Bauer Michael
Published: April 2016

Impaired hepatic function is a common event in intensive care unit patients and as the liver plays a central role in drug metabolism and excretion this may lead to profound changes in pharmacokinetics. Underlying mechanisms are altered enzyme function of phase I and phase II metabolism, altered transporter protein function together with cholestasis and hepatic perfusion disorders. Moreover, multidrug therapy may lead to induction and inhibition of these enzymes and transporter proteins. In addition, changes in plasma protein binding and volumes of distribution of drugs are common. Altogether, these changes may not only lead to sometimes unpredictable plasma levels of xenobiotics, but also to drug-induced liver injury when hepatocellular accumulation of noxious substances occurs. Concomitant renal dysfunction may further complicate this situation. Pharmacodynamic alterations might also occur. In conclusion, the clinician must carefully evaluate medication given to patients with hepatic failure. Therapeutic drug monitoring should be performed wherever available to guide therapy.
Normal physiology of nutrition
Authors: Blaser Annika Reintam , Deane Adam M.
Published: April 2016

Energy is derived from three major categories of macronutrient—carbohydrate, lipid, and protein. While energy requirements to maintain stable weight can be estimated, it is uncertain if meeting these energy requirements improves outcomes in the critically ill. In health, excess energy is stored via non-oxidative metabolism and during periods of inadequate energy delivery catabolism of storage products occurs. Both storing and using the stores cost energy, each may require up to quarter of energy contained in stored nutrient. Excess carbohydrate stored as glycogen is easily available, albeit in a limited amount. Storage of lipid is the largest energy repository, but requires complex metabolism and is limited by low oxidative capacity. Protein catabolism normally contributes less than 5% of energy requirements, but during periods of inadequate energy delivery or increased catabolism there is a marked increase in endogenous protein breakdown.
Peritoneal dialysis in the critically ill
Authors: Sirota Jeffrey C. , Teitelbaum Isaac
Published: April 2016

Peritoneal dialysis, the first modality of renal replacement therapy used in patients with acute kidney injury, has now largely been supplanted by haemofiltration and haemodialysis. However, as acute kidney injury becomes more common and the need for renal replacement therapy increases, the technical advantages of peritoneal dialysis have made it an increasingly attractive option in acute settings, particularly in resource-deprived areas where haemodialysis is not available. Peritoneal modality can offer distinct advantages over haemodialytic techniques in patients with certain concomitant conditions. A variety of infectious, mechanical, pulmonary, and metabolic complications are possible with peritoneal dialysis, but the incidence of these is low in the acute setting. While not yet studied in robust comparative trials against the various haemodialytic modalities, there is some emerging evidence that peritoneal dialysis can provide adequate renal replacement therapy in acute settings, and acute peritoneal dialysis should be considered when haemodialysis is not available or its attendant complications are undesired.
Normal anatomy and physiology of the brain
Authors: Ferioli Simona , Shutter Lori
Published: April 2016

An understanding of the normal anatomy of the brain is essential to the diagnosis of a number of conditions that may be encountered in patients in the intensive care unit (ICU). Common structural cerebral conditions causing patients to be admitted to the ICU include cerebral trauma (traumatic brain injury), cerebrovascular accidents (both ischaemic and haemorrhagic), and infections. Cerebral conditions with a structural basis occurring after admission to the ICU are not as common as functional abnormalities, such as delirium, and peripheral complications, such as critical illness neuropathy and myopathy. An understanding of brain physiology, in particular factors that control or influence intracranial pressure (ICP) and cerebral blood flow (CBF) underpin much of the theory behind the management of acute brain injuries and syndromes.
Imaging the central nervous system in the critically ill
Authors: Bodart Olivier , Laureys Steven
Published: April 2016

Imaging techniques play a major role in managing patients with acute severe neurological signs. Initial evaluation of patients with traumatic brain injuries is best performed with a computed tomography (CT) scan, both for its ability to demonstrate most of the significant lesions and for logistical reasons. Magnetic resonance imaging (MRI) is able to provide more subtle information, as well as prognosis indicators, but is impractical until the patient’s condition has been stabilized. MRI has the same advantages for assessing anoxic brain injuries. In strokes, MRI has become the technique of choice, as it is able to highlight new lesions among older ones, and can identify ischaemic lesions only a few minutes after the event. At the same time MRI can identify or exclude contraindications for intravenous thrombolysis. Subarachnoid haemorrhages are best initially assessed with CT followed by a digital suppression angiogram to identify arterial aneurysms or arteriovenous malformations. In spine imaging, CT scan works the best in indicating traumatic bone lesions, while MRI is unsurpassed in examining the spinal cord and ligamentous injuries, and can provide prognostic indicators of the expected functional outcome.
Causes and epidemiology of agitation, confusion, and delirium in the ICU
Authors: Vasilevskis Eduard E. , Ely E. Wesley
Published: April 2016

Confusion is a non-specific, non-diagnostic term to describe a patient with disorientation, impaired memory, or abnormal thought process. Agitation describes an increased level of psychomotor activity, and anxious or aggressive behaviour. Many agitated patients may also be delirious, yet they only represent a minority of all delirious patients. ICU delirium is an acute cognitive disorder of both consciousness and content of thought. The hallmark of ICU delirium is a fluctuating mental status, inattention, and an altered level of consciousness. Delirium is the end product of a sequence of insults and injury that lead to a common measurable manifestation of end-organ brain injury. It does not have a single aetiology, but often has multiple different and potentially interacting aetiologies. Both non-modifiable and modifiable risk factors play important roles in the development of delirium. Importantly, the new onset of delirium should prompt the physician to investigate the underlying cause. Cognitive impairment and age are among the most important non-modifiable risk factors, whereas administration of benzodiazepines is the greatest. The alpha-2 adrenoceptor agonist dexmedetomidine shows promise as a sedative reducing the risk for delirium when compared with benzodiazepines.
Causes and diagnosis of unconsciousness
Authors: Stevens Robert D. , Kornbluth Joshua
Published: April 2016

Changes in consciousness are seen in a range of physiological and pathological settings including sleep, anaesthesia, brain lesions, metabolic disturbances, and complex partial or generalized seizures. In neurobiological terms, consciousness may be viewed as having an arousal dimension and an awareness dimension phenotypically expressed as the capacity to respond to self or environmental stimuli. Loss of consciousness is associated with lesions that disrupt neuronal systems in the brainstem and diencephalon that mediate arousal or thalamocortical or corticocortical systems that mediate awareness. As there are many causes of unconsciousness, a timely and focused history and neurologic examination are critical to defining the differential diagnosis.
Diagnosis and assessment of stroke
Authors: Delcourt Candice , Anderson Craig
Published: April 2016

Approximately 20 million strokes occur in the world each year and over one-quarter of these are fatal. This makes stroke the second most common cause of death, after ischaemic heart disease, and strokes are responsible for 6 million deaths (almost 10% of all deaths) annually. Stroke has major consequences in terms of residual physical disability, depression, dementia, epilepsy, and carer burden. Moreover, around 20% of survivors experience a further stroke or serious vascular event within a few years of the index event. Ischaemic stroke contributes the greatest share of the impact of stroke, with a rate of approximately 1 in 1000 person-years and accounting for between 60% (in Asia) and 90% (in Western ‘white’ populations) of all strokes around the world. Diagnosis and assessment are essentially clinical and confirmed by CT or MRI scanning. Prognostication is difficult in the early phase of haemorrhagic stroke and in ischaemic stroke is affected by the availability and timely use of treatments to recanalize the occluded vessel.
Management of parenchymal haemorrhage
Authors: Delcourt Candice , Anderson Craig
Published: April 2016

Parenchymal intracerebral haemorrhage (ICH) affects several million people in the world each year, most of whom reside in developing countries. ICH accounts for 10-40% of strokes and is the least treatable form of stroke with a 30-day mortality of 30-55%, with half of these deaths occurring within the first few days of onset. . High blood pressure is both a causal and prognostic factor for ICH, with early control of hypertension being the only medical treatment which may improve recovery and the level of residual functioning. The role of surgery remains controversial. Management is largely supportive and aimed at reducing further brain injury and preventing complications.
Management of non-traumatic subarachnoid haemorrhage in the critically ill
Authors: Rao Chethan P. Venkatasubba , Suarez Jose Ignacio
Published: April 2016

Non-traumatic subarachnoid haemorrhage (ntSAH) is a complex disease affecting multiple systems and the hospital course of affected patients can be variable. ntSAH is associated with high morbidity and mortality, with the causes of early deaths being either rebleeding or hydrocephalus. The risk of rebleeding is reduced by immediate control of arterial blood pressure and early securing of ruptured aneurysms by either endovascular coiling or surgical clipping. Ongoing management focuses on prevention, detection, and management of delayed neurological deficits. Current recommendations include prophylactic use of nimodipine, maintenance of hypertension and euvolaemia or hypervolaemia, and endovascular treatment of vasospasm that fails to respond to medical therapy. Systemic complications following ntSAH include myocardial injury, acute lung injury, venous and pulmonary thromboembolism, fluid and electrolyte abnormalities, and severe sepsis. Each of these complications should be treated on its merits. Due to the complexity of management patients with ntSAH should be treated in a critical care environment by a collaborative team of neurosurgeons, neuroradiologists, neurologists and intensivists.
Pathophysiology, causes, and management of non-traumatic spinal injury
Authors: Flower Oliver , Partlin Matthew Mac
Published: April 2016

Non-traumatic spinal cord injury (NTSCI) is at least as common as traumatic spinal cord injury (TSCI). It affects both sexes equally and an older population than TSCI. It is a devastating condition with immense functional implications for the individuals involved. There is a wide spectrum of aetiologies with varying pathophysiology and knowledge of these is important to avoid delay in diagnosis and time-critical treatment. The most common causes described in case series in developed countries are degenerative disc disease, canal stenosis, tumours, vascular diseases and inflammatory conditions. History and examination may help direct investigations, but magnetic resonance imaging is usually required. Management of NTSCI focuses on diagnosing and treating the precipitating cause, supportive management, and preventing complications. The outcomes of non-traumatic spinal cord injury are similar to those of traumatic spinal cord injury and depend on the grade and level of injury, pre-morbid status, and concurrent co-morbidities.
Diagnosis, assessment, and management of tetanus, rabies, and botulism
Authors: Lipman Jeffrey , Boots Robert J.
Published: April 2016

Tetanus, rabies and botulism are all infections characterized by the production of a neurotoxin, and generally do not give rise to a systemic inflammatory response. Typically tetanus result from the infection of wounds by the ubiquitious soil-borne bacteria Clostridium tetanii, botulism is most commonly due to toxin produced in food contaminated with Clostridium botulinum. Rabies usually results from an animal bite infected with the rabies virus of the Lyssavirus group. Neurological involvement by all three infections is characterized by paralysis and autonomic instability with tetanus also being associated with muscular rigidity. Importantly, the autonomic dysfunction of tetanus can be severe and may necessitate prolonged treatment in an intensive care unit (ICU). Active immunization can prevent or minimize the symptoms of tetanus and rabies, while passive immunization may slow symptom progression in botulism. Intensive care support is often required to manage respiratory failure and autonomic dysfunction. Rabies is typically fatal in the absence of prior immunization.
Diagnosis, assessment, and management of Guillain–Barré syndrome
Authors: Brealey David , Hirsch Nicholas
Published: April 2016

The Guillain–Barré Syndrome describes a spectrum of acute inflammatory polyneuropathies and is the commonest cause of acute flaccid paralysis within the western world. The pathophysiology is complex and poorly understood, but appears to be an immune-mediated destruction of either the myelin sheath and/or the axons, predominantly of motor nerves. The clinical presentation is classically a rapid, ascending, flaccid paralysis, with minimal sensory deficit. This may ascend to involve respiratory or bulbar muscle function. These patients need careful monitoring and, if deteriorating, should be electively intubated and ventilated. Autonomic instability and sensory disturbance, including pain, is common. Treatment of the underlying condition relies upon immunomodulation with either intravenous immunoglobulin or plasma exchange. Supportive care is aimed at maintaining a safe airway, ventilatory support, and managing the complications of autonomic dysfunction and prolonged immobility. Mortality rates range up to 20%, but are significantly better in specialist neuromedical units. Survivors are often left with significant disability.
Diagnosis, assessment, and management of hyperthermic crises
Authors: Thornton Kevin , Gropper Michael
Published: April 2016

Malignant hyperthermia, the neuroleptic malignant syndrome (NMS), and the serotonin syndrome are the principal disorders associated with life-threatening hyperthermia in the intensive care unit. While each is a clinically unique entity, all can progress to multisystem organ dysfunction with acidosis, shock, and death. MH usually results from exposure to halogenated volatile anaesthetics and/or succinylcholine and symptoms of increased CO2 production and respiratory acidosis progress rapidly without prompt intervention, including the administration of dantrolene. NMS is a syndrome of rigidity and altered mental status seen most commonly in patients being treated with antipsychotic medications. The serotonin syndrome is seen in patients treated with serotonergic agents including selective serotonin reuptake or monoamine oxidase inhibitors and tricyclic antidepressants. The salient clinical finding is clonus, but agitation, altered mental status and autonomic dysfunction are common. Recognizing the non-specific features of these syndromes presents a challenge as they are life-threatening if not treated promptly and correctly with specific therapies.
Disorders of sodium in the critically ill
Authors: Corwin Howard L. , McIlwaine John K.
Published: April 2016

Disorders of plasma sodium concentration, hyponatraemia and hypernatraemia, are among the most common clinical problems observed in the critically ill. These disorders are often asymptomatic, although in some patients they may result in symptoms ranging in severity from minor to life threatening. Treatment of is primarily dependent on symptoms, although the acuteness of the disorder is also a consideration. The approach to the treatment of these disorders in individual patients involves balancing the risk of treatment versus the risk the disorder itself. More severe symptoms tend to occur with acute presentations, while too rapid correction can lead to complications.
Disorders of potassium in the critically ill
Authors: Frise Matthew C. , Salmon Jonathan B.
Published: April 2016

Plasma potassium levels are maintained in health between 3.5 and 5.0 mmol/L, and reflect total body potassium only in stable states at normal pH. Most true hyperkalaemia results from renal insufficiency. The goals of therapy are myocardial protection and return of plasma potassium to a safe level. Measures are commonly initiated above 5.5 mmol/L; above 6.5 mmol/L, aggressive measures should be adopted and calcium salts given if there are cardiac dysrhythmias or QRS-broadening. Glucose-insulin infusions and beta-2-agonists promote potassium shifts into cells. Diuretics and sodium bicarbonate may be helpful, but persistent hyperkalaemia is an indication for renal replacement therapy. Hypokalaemia may lead to dangerous arrhythmias, skeletal muscle weakness, ileus, and reduced vascular smooth muscle contractility. Rapid replacement should only be undertaken for severe hypokalaemia or in the context of arrhythmias. Once the extracellular deficit is corrected, there will usually be a continuing need for potassium supplementation to replenish intracellular stores.
Disorders of calcium in the critically ill
Authors: Rosengart Matthew R.
Published: April 2016

Calcium is vitally important for normal cellular signalling and function. However, its toxicity necessitates that intracellular calcium concentration [Ca2+] be tightly regulated and compartmentalized. Evolutionary pressures have yielded several regulatory mechanisms to maintain intracellular and extracellular ionized calcium concentrations compatible with life. During periods of critical illness these process are commonly overwhelmed, and disorders of calcium homeostasis are highly prevalent among intensive care unit (ICU) patients. Indeed, hypocalcaemia occurs in up to 88% of critically-ill ICU patients suffering from trauma, sepsis, and burns. Contemporary evidence suggests that although hypocalcaemia may be associated with ICU mortality, it is not in the causal pathway. A systematic review concluded there are no data to support the routine parenteral administration of calcium in the management of asymptomatic critical illness-related hypocalcaemia. Asymptomatic hypocalcaemia of critical illness does not necessitate replacement. However, acute, symptomatic hypocalcaemia necessitates parenteral supplementation to prevent tetany, seizures, and cardiac arrhythmias
Pathophysiology, causes, and management of metabolic alkalosis in the critically ill
Authors: Brimioulle Serge
Published: April 2016

Metabolic alkalosis occurs in up 51% of abnormal acid-base samples in the hospital. It is characterized by a primary increase in bicarbonate concentration and is always associated with chloride depletion. In critically-ill patients, it is most often generated by diuretic administration, digestive losses, alkali administration, or rapid correction of hypercapnia. Even after all causal factor are removed, it can be maintained by blood volume depletion and potassium depletion. Metabolic alkalosis results in hypercapnia, hypoxaemia, cardiac arrhythmias, altered consciousness, and neuromuscular hyperexcitability. It is first treated by removing the causal factors, whenever possible. Maintaining factors must be reversed by sodium chloride and/or potassium chloride administration. Acetazolamide and renal replacement therapy, when given for specific indications, can also correct the alkalosis. Lysine and arginine chloride are no longer used. If metabolic alkalosis is severe or when other treatments are contraindicated or ineffective, hydrochloric acid infusion is useful. Dilute hydrochloric acid can be infused safely, provided adequate precautions are taken to prevent extravascular leakage, vessel damage, and tissue necrosis.
Pathophysiology of glucose control
Authors: Madl Ulrike
Published: April 2016

Hyperglycaemia is a frequent phenomenon in critically-ill patients, associated with increased morbidity and mortality. Hyperglycaemia results in cellular glucose overload and toxic adverse effects of glycolysis and oxidative phosphorylation, especially in tissues with insulin-independent glucose uptake, and acute hyperglycaemia can exert a variety of negative effects. It is the main side effect of intensive insulin therapy. Both severe and moderate hypoglycaemia are independent risk factors of mortality in critically-ill patients. Prolonged hypoglycaemia induces neuronal damage, but may also have adverse cardiovascular effects. Several risk factors predispose critically-ill patients to hypoglycaemic events. Rapid glucose fluctuations may induce oxidative stress and lead to vascular damage. Glucose complexity is a marker of endogenous glucose regulation. Association between hyperglycaemia and outcome is weaker in diabetic critically-ill patients than in non-diabetic patients. Pre-admission glucose control in diabetic critically-ill patients plays a role in the response to glucose control and mortality.
Glycaemic control in critical illness
Authors: Finfer Simon
Published: April 2016

Hyperglycaemia is a near universal occurrence in critically-ill patients. In the last 10 years, control of blood glucose has been one of the most intensively studied areas of critical care medicine. It has become clear that control of blood glucose has the potential to affect both morbidity and mortality, and considerable uncertainty remains over many aspects of blood glucose management. Both hyperglycaemia and hypoglycaemia are associated with increased mortality and should be avoided wherever possible. Wide fluctuations in blood glucose concentration (referred to as increased glucose variability) are also associated with increased mortality, but may indicate more severe illness. Increased interest in blood glucose management has demonstrated that point-of-care glucose meters designed for ambulatory use by patient with diabetes are not sufficiently accurate for use in critically-ill patients. More accurate analysers should be used in the intensive care unit and management guided by computerized. Future developments may see the introduction of accurate continuous or near continuous blood glucose analysers, but safe and effective closed loop control of blood glucose remains an elusive goal.
Pathophysiology and management of thyroid disorders in the critically ill
Authors: O’Dwyer Michael , Watson David
Published: April 2016

Although overt thyroid disease as a primary admission diagnosis to an intensive care unit is uncommon, failure to recognize and adequately manage this condition can have fatal consequences. Hyperthyroidism is usually manifested by signs and symptoms of an exaggerated sympathomimetic response. In its most severe forms, a thyroid storm will necessitate a multimodal treatment. Although robust evidence is lacking, radiographic contrast dyes containing iodine are becoming popular as a first-line treatment. Hypothyroidism can similarly present as a diagnostic dilemma, particularly in the elderly. Management is difficult with little consensus as to the optimal pharmacological approach. Treatment should be individually tailored, while remaining vigilant for the unwanted side effect of treatment with thyroid hormones. In contrast, sick euthyroid syndrome is commonly observed in the critically ill. A sound understanding of the action of thyroid hormones in health and in the critically ill will benefit clinicians in recognizing these disorders and also in guiding their management in an area where significant variability remains in therapeutic approaches.
Apheresis in the ICU
Authors: Sternbach Marion
Published: April 2016

This chapter describes therapeutic plasma exchange, as well as cytapheresis for hyperleukocytosis and essential thrombocythemia, as well as harvesting haematological stem cells (HSC) for transplantation. Instrumentation and techniques are mostly density centrifugation, much less column adsorption for antibodies or membrane filtration for noxious molecules. Pathophysiology of apheresis is dealt with in great detail with emphasis on prevention and treatment of side effects, much more critical in the intensive care unit (ICU) setting. Main manifestations are: hypocalcaemia due to chelation by anticoagulants, hypo- and less hypervolaemia, allergic reactions to sedimenting and volume replacement starches or plasma, depletion of coagulation factors, vitamin K, immunoglobulins, lymphocytes with long lifespan and platelets. Wash-out of drugs for comorbid or underlying conditions occurs inadvertently. Main indications for plasma exchange are thrombotic thrombocytopenic purpura (TTP)/haemolytic uraemic syndrome (HUS) with plasma or cryo-poor supernatant (based on RCT), hyperviscosity syndromes, post-transfusion purpura (PTP) and auto-immune haemolytic anaemia (AIHA), where all other treatments have failed. In cold agglutinin disease, cryoglobulinaemia, coagulation factor inhibitors and ABO incompatible HSC transplants, plasmapheresis has proven useful. Myeloma with renal failure does not seem to benefit significantly from plasma exchange (randomized controlled trials proven).
Pathophysiology of disordered coagulation
Authors: Stanworth Simon , McKechnie Stuart
Published: April 2016

Imbalances in the regulation of haemostasis may manifest as bleeding (depletion of pro-coagulant factors) or thrombosis (deficiency of anti-coagulants). Disordered haemostasis is common in critically-ill patients and may result from infection, trauma, haemorrhage, inflammation, organ dysfunction (notably renal and liver dysfunction), or drug therapy. Complex patterns of coagulopathy where both bleeding and prothrombotic tendencies co-exist are well recognized in critical illness. The limitations of standard laboratory coagulation tests to predict bleeding risk, including activated partial thromboplastin time and prothrombin time, are well recognized. These assays were developed for diagnosis of inherited bleeding disorders or for monitoring of anticoagulant therapy. This has led to increased interest in global haemostatic tests, such as viscoelastic and thrombin generation tests. Thromboembolism is an important cause of morbidity and mortality in critically-ill patients. While inherited causes of bleeding appear to be often related to single gene abnormalities, thrombotic tendencies appear to reflect more complex interactions between inherited and acquired factors. Many interactions exist between coagulation pathways and inflammation. Systemic inflammation triggers widespread activation of coagulation, with pro-inflammatory cytokines activating pro-coagulant pathways and downregulating anticoagulant pathways. A net result of this interaction between inflammatory and coagulation pathways in sepsis is thrombin generation, intravascular fibrin deposition and a consumptive coagulopathy.
Pathophysiology and management of neutropenia in the critically ill
Authors: Champigneulle Benoit , Pène Frédéric
Published: April 2016

Neutropenia is defined by an absolute neutrophil count <500 per mm3. Chemotherapy-induced myelosuppression represents the main mechanism accounting for neutropenia, although various bone marrow disorders might also result in impaired granulopoiesis. Neutropenia, especially when profound and prolonged, is a major risk factor for severe bacterial and fungal infections. Early initiation of empirical broad-spectrum antibiotic therapy represents the cornerstone of the treatment of febrile neutropenia. A number of infected neutropenic patients may exhibit organ failures, such as acute respiratory failures and/or severe sepsis requiring intensive care unit (ICU) admission. This chapter discusses the particularities in the management of neutropenic patients in the ICU, including outcome and criteria for ICU admission, management of antimicrobials with respect to the current epidemiological trends, and other measures specific to this subgroup of patients.
Sickle crisis in the critically ill
Authors: Jain Shilpa , Gladwin Mark T.
Published: April 2016

Sickle cell disease crises are precipitated by an acute occlusion of microvessels, which can lead to end organ ischaemia reperfusion injury and acute haemolysis. Acute fat emboli syndrome, acute lung injury (the acute chest syndrome), acute pulmonary hypertension, and cor pulmonale, haemorrhagic and occlusive stroke, and systemic infection represent the most common life-threatening complications observed in current ICU practice. General principles of management in all patients admitted to the critical care unit are hydration, antibiotics, pain control, and maintenance of oxygenation and ventilation. Red blood cell transfusion therapy is the treatment of choice for most complications of sickle cell disease requiring intensive care management. Transfusion of sickle negative, leukoreduced red blood cells, phenotypically matched for Rhesus and Kell antigens is the minimum standard of care in sickle cell disease patients as they have a high incidence of red blood cell alloimmunization.
Principles and prevention of pressure sores in the ICU
Authors: Crawford Laura , Kleinpell Ruth
Published: April 2016

A pressure ulcer, defined by the National Pressure Advisory Panel and European Pressure Ulcer Advisory Panels as localized injury to the skin or tissue as the result of pressure or pressure in combination with shear, can be an adverse complication of a hospital stay, especially for acute and critically-ill patients. Factors that can contribute to pressure ulcer development include the intensity and duration of pressure, tissue tolerance, shear, and friction. Common anatomical sites for pressure ulcers development are over bony prominences. The National Pressure Advisory Panel and European Pressure Ulcer Advisory Panels define pressure ulcers in six stages according to the degree of tissue damage present in the wound. A risk assessment should be performed to identify the vulnerability of pressure ulcer development and provide guidance for the implementation of preventative interventions. For the critically-ill patient, several specific measures are advocated for preventing pressure ulcers.
Novel biomarkers of infection in the critically ill
Authors: Huang David T. , Sen Ayan
Published: April 2016

Over 25% of all annual deaths in the world are due to infection. Early diagnosis and risk stratification facilitate timely and specific treatment, but are complicated by the highly variable and non-specific nature of the signs and symptoms of sepsis. There is a lack of a ‘gold standard’ for the diagnosis of infection or sepsis, prognosis of severe infections, and sepsis. There are several biomarkers that have been investigated in literature like white blood count, C-reactive protein, procalcitonin, sTREM1, etc., with equivocal results. White blood count and C-reactive protein are elevated in states of inflammation without infection and sepsis. Therefore, they have low specificities for diagnosis of infection. The future is promising with development of high sensitivity assays, molecular strategies, and a ‘panel approach’, all of which need to be investigated in well-designed future studies. At present, there is insufficient evidence for the routine use of novel biomarkers in infection and sepsis.
Healthcare worker screening for nosocomial pathogens
Authors: Van Buynder Paul , Brodkin Elizabeth
Published: April 2016

Health care organizations and their staff have a responsibility to prevent occupationally-acquired infections and avoid transmitting disease to patients. As well as being a known source of nosocomial infections, health care workers (HCWs) are at risk themselves of becoming infected in the workplace. Regulatory authorities in many countries advise or mandate screening for key blood-borne pathogens (BBPs) in settings where transmission between patients and staff is possible. Staff infected with a BBP are restricted from performing certain procedures. In addition to screening for BBP, health care organizations require a tuberculosis infection control programme. Routine screening of health care workers for other organisms such as MRSA is usually not indicated. Health care organizations should have robust policies to immunize health care workers against Hepatitis B and respiratory diseases. Many organizations now make immunization against key respiratory diseases a pre-requisite for employment as a key infection control patient safety strategy.
Environmental decontamination and isolation strategies in the ICU
Authors: Slater Leigh Ann , Lipsett Pamela A.
Published: April 2016

Potential avenues for infection transmission range from the initial hospital construction itself to unit and room layout, design materials, disinfection materials and methods, isolation equipment, and staff ratios and training. Better understanding of these avenues for transmission will suggest the means to decrease the burden of environmental contamination. There is a limited evidence base for many currently employed cleaning and isolation techniques. Many are simply intuitive or based on non-controlled observations, and rigorous studies may be prohibitively expensive. In addition, reduced colonization does not always translate to reduced infection rates. This chapter will provide a brief overview of the current understanding of the environment of care and its impact on infection control practices.
Antimicrobial selection policies in the ICU
Authors: Paterson David L. , Hayashi Yoshiro
Published: April 2016

Antibiotic selection is a crucial drug choice in critically-ill patients. Optimization of empiric antibiotic choice can be gained by knowledge of the site of infection and the probable causative organisms at that site. This should be linked with knowledge of the local epidemiology of antibiotic resistance in the actual intensive care unit housing the patient. Initial empiric antimicrobial choice may need to be broad in order to cover potential antibiotic-resistant pathogens. However, it is important to be prudent in antibiotic strategy since the selection of multiple-resistant organisms by excessively broad or prolonged antibiotic therapy may affect not just the patient undergoing antibiotic therapy, but also other future patients. Selection of appropriate antibiotic regimens can be facilitated by the use of technology such as MALDI-TOF for rapid bacterial identification. Consultation with infectious disease physicians or specialist pharmacists may also be warranted in order to optimize antibiotic dosing, duration of infusion and frequency of administration, so as to meet pharmacodynamics targets linked to improved patient outcome.
Drug-induced depression of immunity in the critically ill
Authors: McCulloh Russell J. , Opal Steven M.
Published: April 2016

Immunosuppressive drugs are among the fastest-growing category of drugs in medicine today, both in terms of new medication development and in terms of use. Glucocorticoids, calcineurin inhibitors, and biological agents, among others, are used in a variety of diseases. . Although often of great benefit to patients, immunosuppressive agents also pose significant long-term risks for opportunistic infection. These drugs can also blunt normal host responses to infection, and patients receiving immunosuppressive medications are at high risk for severe illness, sepsis, and death from opportunistic infections. Knowledge of immunosuppressive agents, their mechanisms of action, effects on the immune system, and commonly-associated infectious complications plays an instrumental role in guiding appropriate diagnostic and treatment plans for immunosuppressed patients. This chapter reviews the most commonly-used immunosuppressive agents today, and provides the reader with the specific effects these medications can have on a patient’s immune system and the potential infectious agents of concern associated with their prolonged use.
HIV in the critically ill
Authors: Hull Mark , Reynolds Steven C.
Published: April 2016

It has been over 30 years since the recognition of the acquired immune deficiency syndrome (AIDS), linked to infection with human immunodeficiency virus (HIV). Opportunistic infections arise in the setting of decreases in the CD4+ T-lymphocyte count. Advances in the safety, and effectiveness of combination antiretroviral therapy (cART) have led to substantial improvements in life-expectancy for individuals accessing successful therapy. As such individuals are likely to be admitted to the intensive care unit (ICU) for conditions un-related to HIV, although presentations due to opportunistic infections and malignancies must be considered in those with previously undiagnosed infection or in those patients non-adherent to cART.. Individuals receiving cART must undergo careful evaluation for potential drug–drug interactions with other medications. Treatment interruption of cART is not generally advised due to risk of rebound viraemia and potential development of resistance.. Immune reconstitution inflammatory syndrome may be considered in those with recent cART initiation.
Diagnosis and management of viral haemorrhagic fevers in the ICU
Authors: Mesquita Emersom C. , Bozza Fernando A.
Published: April 2016

In a globalized scenario where widespread international travel allows viral agents to migrate from endemic to non-endemic areas, health care providers and critical care specialists must be able to readily recognize a suspected case of viral haemorrhagic fever (VHF). Early suspicion is pivotal for improving patient outcome and to ensure that appropriate biosafety measures be applied. VHFs are acute febrile illnesses marked by coagulation disorders and organ specific syndromes. VHFs represent a great medical challenge because diseases are associated with a high mortality rate and many VHFs have the potential for person-to-person transmission (Filoviruses, Arenavioruses, and Bunyaviroses). Dengue is the most frequent haemorrhagic viral disease and re-emergent infection in the world and, due to its public health relevance, severe dengue will receive special attention in this chapter. The diagnosis of VHFs is made by detecting specific antibodies, viral antigens (ELISA) and viral nucleic acid (RT-PCR) on blood samples. Supportive care is the cornerstone in the treatment of VHFs. Ribavirin should be started as soon as a case of VHF is suspected and discontinued if a diagnosis of Filovirus or Flavivirus infection is established. Adjunctive antimicrobial therapy is usually implemented to treat co-existing or secondary infections. Antimalarial treatment should also be initiated if a malaria test (thick blood films) is not quickly available and/or reliable and patients travel history is compatible. It is always recommended to apply appropriate biosafety measures and notify local infection control unit and state and national authorities.