bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnosis, assessment, and management of myasthenia gravis and paramyasthenic syndromes
Authors: Reddy Ugan , Hirsch Nicholas
Published: April 2016

Diseases that affect the neuromuscular junction (NMJ) interfere with normal nerve transmission and cause weakness of voluntary muscles. The two most commonly encountered are acquired myasthenia gravis (MG) and the Lambert–Eaton myasthenic syndrome (LEMS). Acquired MG is an autoimmune disease in which antibodies are directed towards receptors at the NMJ. In 85% of patients, IgG antibodies against the postsynaptic acetylcholine receptor (AChR) are found (seropositive MG). The thymus gland appears to be involved in the production of these which cause an increase rate of degradation of AChR resulting in a decreased receptor density resulting in a reduced postsynaptic end-plate potential following motor nerve stimulation and leading to muscle weakness. Although all voluntary muscles can be affected, ocular, bulbar, respiratory, and proximal limb weakness predominates. In the majority of seronegative patients, an antibody directed towards a NMJ protein called muscle specific tyrosine kinase (MUSK) is found. Anti-MUSK MG is characterized by severe bulbar and respiratory muscle weakness. Diagnosis of MG requires a high degree of clinical suspicion coupled with pharmacological and electrophysiological testing, and detection of the various causative antibodies. Treatment of MG involves enhancing neuromuscular transmission with long-acting anticholinesterase agents and immunosuppression. Acute exacerbations are treated with either plasma exchange or intravenous immunoglobulin. Myasthenic crisis is associated with severe muscle weakness that necessitates tracheal intubation and mechanical ventilation. LEMS is an autoimmune disease in which IgG antibodies are directed towards the pre-synaptic voltage-gated calcium channels at the NMJ. It is often associated with malignant disease (usually small cell carcinoma of the lung). Autonomic dysfunction is prominent and patients show abnormal responses to neuromuscular blocking drugs.
Diagnosis, assessment, and management of ICU-acquired weakness
Authors: Hart Nicholas , Sharshar Tarek
Published: April 2016

Intensive care unit-acquired weakness (ICU-AW) is the term applied to generalized skeletal muscle weakness developed as a result of critical illness. This condition adversely affects up to three-quarters of patients admitted to the intensive care unit and it is associated with risk factors such as illness severity and duration of mechanical ventilation. Using detailed electrophysiological tests and histological muscle sampling, ICU-AW can be classified as a neuropathy, myopathy, or a neuromyopathy. However, this detailed approach is generally only required when there is diagnostic uncertainty and a simple test to diagnose ICU-AW utilizing manual muscle testing and the Medical Research Council (MRC) sumscore are more commonly employed. Nonetheless, short- and long-term outcomes associated with developing ICU-AW using MRC sumscore, have been reported. Intervention exercise therapy and rehabilitation strategies are required to minimize the effects of developing of skeletal muscle wasting.
Normal physiology of the endocrine system
Authors: Baudouin Simon , Ball Steve
Published: April 2016

The endocrine system describes an array of chemical signals (hormones). Working in concert with the nervous system, the endocrine system forms a complex neurohumoral network, communicating changes in the environment to facilitate adaptive responses and serving to integrate those responses in a coherent, coordinated manner. The endocrine system has inherent rhythmicity, which has important implications for the integration and coordination of metabolism, and how we measure endocrine signals in clinical settings. At a cellular level, hormone action is mediated through a series of discrete, but interacting signal transduction pathways. This chapter outlines a functional design approach to endocrinology; providing a framework covering the principles of hormone regulation and hormone action—critical for understanding the role of the endocrine system in physiology and pathophysiology.
Disorders of phosphate in the critically ill
Authors: Geerse Daniël A. , Schultz Marcus J.
Published: April 2016

Phosphorus plays an important role in many cellular processes and hypophosphataemia can result from a number of causes. Critically-ill patients are at increased risk for developing hypophosphataemia due to the presence of multiple causal factors. Hypophosphataemia may lead to a multitude of symptoms and frequent monitoring of serum phosphate is advised in critically-ill patients is recommended and should be corrected in patients with associated symptoms. It is uncertain whether correction in apparently asymptomatic patients affects outcome, although treatment is generally recommended for severe hypophosphataemia. Multiple strategies of intravenous phosphate administration have been described, but it is unknown which strategy is superior. Hyperphosphataemia is most often caused by renal insufficiency, but can also be caused by increased intake or release from damaged cells. Symptoms are mainly associated with subsequent hypocalcaemia and correction of hyperphosphataemia can be achieved by minimizing the intake of phosphate, increasing renal phosphate excretion, and renal replacement therapy.
Pathophysiology and causes of metabolic acidosis in the critically ill
Authors: Neligan Patrick J. , Deutschman Clifford S.
Published: April 2016

Critical illness is typically characterized by changes in the balance of water and electrolytes in the extracellular space, resulting in the accumulation of anionic compounds that manifests as metabolic acidosis. Metabolic acidosis manifests with tachypnoea, tachycardia, vasodilatation, headache and a variety of other non-specific symptoms and signs. It is caused by a reduction in the strong ion difference (SID) or an increase in weak acid concentration (albumin or phosphate). Increased SID results from hyperchloraemia, haemodilution or accumulation of metabolic by-products. A reduction in SID results in a corresponding reduction is serum bicarbonate. There is a corresponding increase in alveolar ventilation and reduced PaCO2. Lactic acidosis results from increased lactate production or reduced clearance. Ketoacidosis is associated with reduced intracellular glucose availability for metabolism, and is associated with insulin deficiency and starvation. Hyperchloraemic acidosis is associated with excessive administration of isotonic saline solution, renal tubular acidosis and ureteric re-implantation. Renal acidosis is associated with hyperchloraemia, hyperphosphataemia, and the accumulation of medley nitrogenous waste products.
Management of metabolic acidosis in the critically ill
Authors: Neligan Patrick J. , Deutschman Clifford S.
Published: April 2016

Metabolic acidosis (MA) commonly complicates critical illness, usually manifesting as a fall in arterial pH (<7.4) accompanied by a concomitant fall in serum bicarbonate concentration. Acidosis caused by unmeasured anions (UMA), can be distinguished from Hyperchloraemic acidosis by demonstrating a widening of the anion gap (AG). AG should be corrected for albumin and lactate. The base deficit (BD) calculates degree of metabolic acidosis and represents the amount of strong cation required to restore the pH to 7.4. Neither the AG nor the BD specify the cause of acidosis, and are unhelpful in the setting of mixed disorders. The base deficit gap (BDG) is used to calculate the effect of free water, sodium, chloride and albumin on the BD. It is the difference between BDcalc and BDmeasured (on a blood gas) and represents UMA. The strong ion gap more robustly calculates the amount of UMA than AG or BDG, and may be more accurate at predicting outcomes in the emergency room. Lactic acidosis is due to hypovolaemia until otherwise proven. In the majority of cases aggressive fluid resuscitation is warranted. In the presence of normal tissue blood flow regional hypoperfusion, poisoning or exogenous catecholamines should be considered. Ketoacidosis is due to intracellular glucose deficiency, caused by hypoinsulinaemia or starvation. The former is treated with isotonic crystalloid and insulin. Renal acidosis is treated with renal replacement therapy or recovery of renal function.
Management of diabetic emergencies in the critically ill
Authors: Mesotten Dieter , Van Cromphaut Sophie
Published: April 2016

The three major diabetic emergencies comprise diabetic ketoacidosis (DKA), hyperglycaemic hyperosmolar state (HHS), and prolonged hypoglycaemia. These complications are preventable, treatable, and rather infrequently lead to prolonged intensive care (ICU) admission. Hyperglycaemic crises, whether DKA in type 1 diabetics, or HHS in type 2 diabetics, are characterized by moderate to severe hypovolaemia, electrolyte disturbances and a potentially life-threatening trigger. Hence, airway–breathing–circulation securement, diagnosis, and treatment of the underlying condition, as well as fluid resuscitation are the cornerstones of the acute management of DKA and HHS. Currently, a continuous, low (physiological) dose insulin scheme intravenously with omission of the priming bolus is advocated to avoid hypoglycaemia. An evidence-based treatment protocol, and reliable blood glucose and electrolyte measurements are compulsory to safely manage these crises until resolution of ketoacidosis or the hyperosmolar state. Profound hypoglycaemia should be suspected in every coma patient with an indistinct history or on a known regimen of insulin or sulphonylurea/meglitinide. This condition warrants immediate and sufficiently long administration of glucose orally or intravenously, as well as repeated monitoring of blood glucose levels. Alternatively, the counter-regulatory hormone glucagon may be injected intramuscularly in the emergency setting.
Pathophysiology and management of adrenal disorders in the critically ill
Authors: Venkatesh Bala , Cohen Jeremy
Published: April 2016

The existence of the syndromes of relative adrenal insufficiency, or critical illness corticosteroid insufficiency, are debatable. In sepsis, there are alterations in plasma cortisol profiles, and corticotropin responsiveness with marked variability in responses between patients. It is probable that the spectrum of plasma and tissue glucocorticoid changes may represent a ‘sick euadrenal state’ analogous to the sick euthyroid state and may not reflect adrenocortical insufficiency. Treatment of acute adrenal crisis should not be delayed for the results of adrenal testing, and should consist of immediate supportive measures, fluid resuscitation, and high-dose intravenous glucocorticoid therapy. Admission to intensive care with a primary diagnosis of hyperadrenalism is uncommon. Patients usually present uncontrolled hypertension, electrolyte abnormalities or encephalopathy.
Pathophysiology and management of pituitary disorders in the critically ill
Authors: Debaveye Yves , Van den Berghe Greet
Published: April 2016

The pituitary gland plays a predominant role in the endocrine system. Consequently, patients with pituitary diseases or after pituitary surgery present unique challenges to the intensivist. Failure of the anterior pituitary gland to secrete one or more pituitary hormones results in a clinical syndrome known as hypopituitarism. While hypopituitarism is mostly encountered in patients in whom the diagnosis has already been made, acute exacerbation of an undiagnosed insufficiency may occasionally occur. Acute decompensated patients with suspected hypopituitarism should be admitted to an intensive care unit for haemodynamic stabilization, replacement of missing hormones, and identification and treatment of the causative stressor. Prompt administration of hydrocortisone is the single most important acute medical intervention in hypopituitaric patients. Failure of the posterior pituitary to secrete antidiuretic hormone results in diabetes insipidus (DI). DI is characterized by excess volumes of severely diluted urine, which can lead to hyperosmolality and hypernatraemia as many critically-ill patients do not have free access to oral fluids due to obtundation or sedation. Management of DI includes the correction of free water deficit and the reduction of polyuria with desmopressin. The post-operative care following pituitary surgery focuses on vigilant observation for neurosurgical complications (visual loss, meningitis, and cerebrospinal fluid leakage) and monitoring of neuroendocrinological perturbations (hypopituitarism and disorders of water balance, such as DI and SIADH). SIADH presents with hyponatremia, hypo-osmolality, and inappropriately concentrated urine in a setting of euvolaemia and can be managed in most cases by fluid restriction. Potential disruption of the pituitary-adrenal function is covered with peri-operative glucocorticoids.
Pathophysiology and management of functional endocrine tumours in the critically ill
Authors: Nikravan Sara , Mihm Frederick
Published: April 2016

Thyroid hormones act on most tissues via nuclear T3 receptors. Thyroid hormones stimulate oxygen consumption and heat production, influence cell growth and maturation (central nervous system, bone), and modulate metabolism (carbohydrates, lipids, proteins, drugs). Treatment for presumed thyroid disease frequently has to be initiated before the results of diagnostic tests are available. Treatment of hyperthyroidism should result in the reduction of serum thyroid hormone levels and their action on peripheral tissues with concurrent treatment of the precipitating event. In severe hypothyroidism the choice of thyroid hormone (thyroxine or tri-iodothyronine), optimal dosing, and the route of administration remain controversial
Coagulation monitoring
Authors: Kuiper Gerhardus J. A. J. M. , ten Cate Hugo
Published: April 2016

Haemostasis is a dynamic process to stop bleeding after vessel wall damage. Platelets form a platelet plug via activation, adherence, and aggregation processes. The coagulation proteins are activated one-by-one, cascading towards fibrin polymerization, a process controlled by thrombin generation. Fibrinolysis is the process responsible for fibrin mesh degradation, which is also controlled by thrombin. Besides procoagulant proteins, anticoagulant proteins maintain a balance in the haemostatic system. Measuring platelet count and function can be done as part of the monitoring of haemostasis, while coagulation times are measured to assess the coagulation proteins. Degradation products of fibrin and lysis times give information about fibrinolysis. Point-of-care monitoring provides simple, rapid bedside testing for platelets and for whole blood using viscoelasticity properties. In trauma-induced coagulopathy (TIC) platelet counts and coagulation times are still common practice to evaluate haemostasis, but point-of-care measurements are being used more and more. Medication interfering with haemostasis is frequently used in intensive care unit patients. Each (group of) drug(s) has its own monitoring tests either based on classical or novel techniques.
Disseminated intravascular coagulation in the critically ill
Authors: Levi Marcel , Schultz Marcus J.
Published: April 2016

Disseminated intravascular coagulation (DIC) is a syndrome characterized by systemic intravascular activation of coagulation, leading to widespread deposition of fibrin in the circulation. In patients with DIC, a variety of altered coagulation parameters may be detectable, such as thrombocytopenia, prolonged global coagulation times, reduced levels of coagulation inhibitors, or high levels of fibrin split products. There is not a single test, however, that is sufficiently accurate to establish or reject a diagnosis of DIC. Nevertheless, a combination of widely available tests may be helpful in making the diagnosis of DIC and can also be helpful in guiding the selection of DIC patients that require specific, often expensive, interventions in the coagulation system. Recent knowledge on important pathogenetic mechanisms that may lead to DIC has resulted in novel preventive and therapeutic approaches to patients with DIC. Strategies aimed at the inhibition of coagulation activation may theoretically be justified and have been found beneficial in experimental and clinical studies. These strategies comprise inhibition of tissue factor-mediated activation of coagulation or restoration of physiological anticoagulant pathways.
Prevention and management of thrombosis in the critically ill
Authors: Chan Chee M. , Shorr Andrew F.
Published: April 2016

Venous thromboembolism (VTE) represents a significant challenge in the care of critically-ill patients. Because of a combination of factors including comorbidities, their acute illness, and medical interventions, patients in the intensive care unit (ICU) face a heightened risk for VTE. In addition, because of their impaired physiological reserves, critically-ill subjects will not tolerate events, such as pulmonary emboli (PEs), well. A number of recent studies better describe the epidemiology and outcomes related to VTE acquired in the ICU. New research also explores optimal approaches for VTE prevention and better defines the risk for bleeding associated with pharmacological preventive options. This chapter reviews the epidemiology of, outcomes related to, and preventive strategies for VTE in the ICU. It also discusses diagnostic options in addition to focusing on selected populations at very high risk for VTE in the ICU, namely trauma patients and those who have suffered a stroke.
Thrombocytopenia in the critically ill
Authors: Kothari Jaimal , Scully Marie
Published: April 2016

Thrombocytopenia is an extremely common finding in patients in intensive care. This can lead to serious morbidity and mortality from bleeding, and also uncertainty with regards to how to assess this risk in the wider context of the underlying pathology, which may be multifactorial, when specific blood products should be transfused, and the associated risks of carrying out interventional procedures. Haemodilution, platelet consumption, increased platelet destruction, reduced production, and increased sequestration are the main mechanisms that account for thrombocytopenia, and in the ICU setting there is typically an interplay of more than one of these that accounts for the counts seen. Sepsis and disseminated intravascular coagulation are the most common causes of thrombocytopenia in the ICU, with significant overlap between the pathologies. Less common causes in an intensive care unit setting include heparin-induced thrombocytopenia (HIT) and thrombotic thromobocytopenic purpura (TTP). The evidence base surrounding platelet thresholds remains poor and is an active area of research. Anticoagulation in the context of thrombocytopenia is problematic and requires a patient-specific approach.
Pathophysiology and management of anaemia in the critically ill
Authors: Walsh Timothy
Published: April 2016

Anaemia is prevalent among the critically ill, with a multifactorial aetiology including haemodilution, iatrogenic blood loss, a reduced red cell lifespan, and especially decreased erythropoiesis. Acute inflammation probably has a major contribution to critical illness-induced anaemia, resulting in reduced iron absorption, sequestration of iron resulting in functional iron deficiency, relative erythropoietin deficiency, and impaired marrow red cell maturation. Anaemia during critical illness resembles the anaemia of chronic inflammatory disease, and probably results from similar pathophysiological processes. Current evidence does not support pharmacological manipulation of this process with iron or erythropoietin. Management should focus on minimization of blood loss and evidence-based use of red cells to maintain haemoglobin level.
Vasculitis in the critically ill
Authors: Keogh Karina A.
Published: April 2016

The vasculitic syndromes are a heterogeneous group of rare disorders characterized by degrees of inflammation and necrosis of blood vessels with a wide variety of clinical manifestations. Intensive care treatment is most commonly required for vasculitis involving small blood vessels, including capillaries. Involvement of these vessels in the lung causes alveolar haemorrhage, which may lead to respiratory failure. In the kidneys it may cause glomerulonephritis leading to renal failure. Severe cardiac, neurological, and gastrointestinal manifestions can also be seen. Non-vasculitic manifestations may also be present, such as pulmonary nodules secondary to granulomatous inflammation in granulomatosis with polyangiitis. Diagnosis is based primarily on history and physical exam in conjunction with radiographic and serological testing. Intensive care unit admission is typically secondary to end organ damage due to inflammation, or because of side effects from the cytotoxic therapies, particularly infection. Treatment of vasculitis includes supportive management in conjunction with immunosuppression. Standard treatment of severe disease consists of corticosteroids and cytotoxic drugs.
Microbiological surveillance in the critically ill
Authors: Wilson A. P. R.
Published: April 2016

Patients in the ICU are at high risk of acquiring multiresistant pathogens. Surveillance quickly identifies outbreaks and promotes antimicrobial stewardship. Catheter-related bacteraemia is often used as a performance measure and intervention using a package of preventative measures can be very successful. Ventilator-associated pneumonia in contrast can be difficult to define accurately. Water sources should be monitored. Pseudomonas aeruginosa may become established in taps and cause invasive infections especially in neonates. Screening of nasal swabs for MRSA followed by topical suppression has been effective in reducing spread during ICU admission. With rising prevalence of multiresistant Gram-negative species, screening of faeces or rectal swabs may become necessary. Acinetobacter is very disruptive if it causes an outbreak and it can be difficult to control. Screening is one method of limiting its’ spread. National surveillance networks are increasing and may be mandatory as they appear to be successful in controlling nosocomial infection.
Oral, nasopharyngeal, and gut decontamination in the ICU
Authors: Oostdijk Evelien , Bonten Marc
Published: April 2016

Many infections are caused by enteric bacilli, presumably from endogenous origin. Selective decontamination of the digestive tract (SDD) was developed to selectively eliminate the aerobic Gram-negative bacilli from the digestive tract, leaving the anaerobic flora unaffected. As an alternative to SDD, investigators have evaluated the effects of selective oropharyngeal decontamination (SOpD) alone. Most detailed data on the effects of SDD and SOpD in ICU-patients come from two studies performed in Dutch ICUs. The Dutch studies provide strong evidence that SDD and SOpD reduce ICUmortality, ICU-acquired bacteraemia with Gram-negative bacteria, and systemic antibiotic use. Although successful application has been reported from several solitary ICUs across Europe, it is currently unknown to what extent these effects can be achieved in settings with different bacterial ecology. More studies are needed on the use of SDD or SOpD as a measure to control outbreaks with multidrug resistant bacteria.
Diagnosis and management of malaria in the ICU
Authors: Whitty Christopher J. M.
Published: April 2016

Falciparum malaria is the commonest life-threatening imported tropical infection. The most important critical care intervention is rapid high-dose antimalarial treatment with artesunate, or if that is not available quinine. The common complications of malaria are different in children and adults. Cerebral malaria may occur in both, for which there is no specific therapy. Renal failure and acute lung injury are much more common in adults, and may occur late in the course of the disease, even after parasites have cleared. In children acidosis, anaemia and Gram-negative sepsis are more common. Renal and respiratory support may be needed in adults. Malaria alone seldom causes shock and if patients are shocked, co-existing Gram-negative sepsis should be considered. In children there is evidence that bolus hydration increases mortality. Most patients make a full recovery even after prolonged periods of unconsciousness.
Pathophysiology of septic shock
Authors: Litell John M. , Shapiro Nathan I.
Published: April 2016

The pathophysiology of sepsis is the result of a dysregulated host response to infection. Interactions between conserved pathogenic signals and host recognition systems initiate a systemic reaction to local infection. Pro- and anti-inflammatory intermediates and associated coagulatory abnormalities lead to altered macrovascular, microvascular, and mitochondrial function. Uncorrected, these processes yield similar patterns of failure in multiple organ systems. Mortality increases with successive organ failures. Although commonly thought to be a manifestation of impaired renal circulation, septic acute kidney injury may be due primarily to non-haemodynamic factors. Pulmonary parenchymal dysfunction in sepsis also contributes to failures in other organ systems. Sepsis involves complex alterations in myocardial function, vascular tone, and capillary integrity, which are mediated by elevated concentrations of inflammatory cytokines, inducible nitric oxide, and reactive oxygen species, among others. Gut hypomotility and translocation of enteric flora likely contribute to a persistent inflammatory response. This perpetuates the pathophysiological pattern of sepsis, and can lead to the delayed onset of these features in patients with other types of critical illness. The neurological manifestations of sepsis include acquired delirium, which is also probably due to circulatory and inflammatory abnormalities, as well as alterations in cerebral amino acid metabolism. Critical illness-related corticosteroid insufficiency and derangements in glucose metabolism are among the endocrine abnormalities commonly seen in septic patients. Restoration of homeostasis requires early haemodynamic resuscitation and aggressive infectious source control.
The host response to trauma and burns in the critically ill
Authors: Bittner Edward A. , Fagan Shawn P.
Published: April 2016

Following severe traumatic injury, patients enter a state of immune dysregulation consisting of both exaggerated inflammation and immune suppression. Traditionally, the host response has been viewed as an early systemic inflammatory response syndrome (SIRS) followed temporally by a compensatory anti-inflammatory or immune-suppressive response syndrome (CARS). While this paradigm has been widely accepted across both medical and scientific fields, recent advances have challenged this concept. The Glue grant investigators recently characterized both the initial inflammatory response to injury and the dynamic evolving recovery process. They found: (1) severe injury produces a rapid (< 12 hours) genomic reprioritization in which 80% of the leukocyte transcriptome is altered; (2) similarities in gene expression patterns between different injuries reveal an apparently fundamental response to severe inflammatory stress, which is far more common than different; (3) alterations in the expression of classical inflammatory and anti-inflammatory as well as adaptive immunity genes occur simultaneously, not sequentially after severe injury; (4) the temporal nature of the current SIRS/CARS paradigm is not supported at the level of the leukocyte transcriptome. Complications are not associated with genomic evidence of a ‘second hit’ and differ only in the magnitude and duration of this genomic reprioritization. Furthermore, the delayed clinical recovery with organ injury is not associated with dramatic qualitative differences in the leukocyte transcriptome. Finally, poor correlation between human and rodent inflammatory genomic responses will alter how the host response is studied in the future.
Host–pathogen interactions in the critically ill
Authors: Geri Guillaume , Mira Jean-Paul
Published: April 2016

Infection by a pathogenic micro-organism triggers a coordinated activation of both innate and adaptive immune responses. The innate immune response quickly triggers an antimicrobial response that will initiate development of a pathogen-specific, long-lasting adaptive immune response. Accurate recognition of microbial-associated molecular patterns by pattern-recognition receptors (PRRs) is the cornerstone of this immediate response. Most studied PRRs are Toll-like receptors (TLRs) and their kinase signalling cascades that activate nuclear transcription factors, and induce gene expression and cytokine production. Deficiencies or genetic variability in these different signalling pathways may lead to recurrent pyogenic infections and severe invasive diseases. After initial contact between the host and pathogen, numerous factors mediate the inflammatory response, as pro-inflammatory cytokines and chemokines. Apart from host genetic variability, pathogen diversity also influences the phenotypic features of various infectious diseases. Genomic analysis may assist in the development of targeted therapies or new therapeutic strategies based on both patient and microorganism genotype.
Neural and endocrine function in the immune response to critical illness
Authors: Ackland Gareth L.
Published: April 2016

The neurohormonal physiological response to various stressors is pivotal for maintaining homeostasis. However, the advent of modern critical care has distorted evolutionary biology by generating the entirely new (patho)physiological entity of critical illness. By extending the biological features of the ‘fight or flight’ response beyond the acute phase, distinct neurohormonal, and immune profiles have become increasingly apparent. Both direct and off-target effects of neurohormonal control on immune function are implicated in the disruption of bidirectional links between neurohormones and immune effectors that limit organ dysfunction. Iatrogenic factors introduced by critical care therapy may exacerbate neurohormonal dysregulation, further distorting the biology of the ‘fight or flight’ response. Neural mechanisms underlying this newly-characterized clinical syndrome remain poorly understood. Furthermore, the same neurohormonal responses are chronically dysregulated in pre-existing comorbidities diseases associated with an increased risk of sepsis, multi-organ failure and critical illness. Off-target local immune effects may explain the failure of clinical trials aimed at altering systemic neurohormonal physiology. Recent laboratory and translational human clinical studies, particularly in diseases characterized by chronic neurohormonal dysregulation, have provided new insights into the possibility of therapeutic interventions that could minimize the pathophysiological features of critical illness.
Immunomodulation strategies in the critically ill
Authors: Maddux Aline B. , Bernard Gordon R.
Published: April 2016

Severe sepsis is a hyperimmune response to an infectious stimulus resulting in a surge of cytokines and mediators of inflammation. High circulating levels of pro-inflammatory cytokines lead to shock, multiple organ failure, and death in septic patients. It has been recognized that patients with sepsis progress into a state of immune paralysis characterized by immune cell apoptosis and high levels of anti-inflammatory cytokines… Anti-inflammatory cytokines suppress production of pro-inflammatory cytokines and inhibit monocytes from presenting antigens to other immune cells. Immune paralysis probably leads to the patient’s inability to clear infections resulting in the delayed mortality observed in some septic patients. Beneficial therapies for sepsis are limited to the mechanical eradication of the source of infection, antibiotics, the judicious use of fluids to support organ perfusion, and oxygen supplementation. Strategies to counteract the hyper- and hypo-immune phases of sepsis have been tried thus far with only minimal success.
Management of β‎-blocker and calcium channel blocker poisoning
Authors: Isbister Geoffrey , Page Colin
Published: April 2016

β‎-blocker and calcium channel-blockers can cause life-threatening toxicity due to cardiogenic shock. Both β‎-blockers and calcium channel-blockers are heterogenous groups of drugs and particular drugs, such as propranolol, diltiazem, and verapamil are far more toxic than the others in their class. The most important investigations in β‎-blocker and calcium channel-blocker overdose are an electrocardiogram, blood glucose measurement, and electrolytes. Like most overdoses, supportive treatment is the most important, with emphasis on the primary pathophysiology. Early decontamination should be considered based on the severity of the poisoning. Treatment of β‎-blockers and calcium channel-blockers poisoning, using absolute blood pressure as an endpoint can be misleading and measuring cardiac output can be more informative in gauging response to treatment. There are no specific antidotes, although β‎-agonists may be effective in β‎-blocker overdose and calcium has been shown to be effective in calcium channel-blocker overdose. The choice of inotropes and/or vasopressors will differ for β‎-blockers and calcium channel-blockers. These include isoprenaline, high dose insulin euglycaemia, phosphodiesterase inhibitors, and other catecholaminergic inotropes for β‎-blocker poisoning and adrenaline, high dose insulin euglycaemia and vasopressors for calcium channel-blocker poisoning.
Management of pesticide and agricultural chemical poisoning
Authors: Hulse Elspeth J. , Eddleston Michael
Published: April 2016

Poisoning with agricultural chemicals is common in rural Asia-Pacific with up to 300,000 annual deaths from pesticide self-poisoning. The pharmacokinetics and pharmacodynamics of pesticides can vary markedly depending on the chemicals ingested, the pesticide’s lipid solubility, enzyme reactivation, co-ingested toxicants, and extent of decontamination and organ dysfunction. Diagnosis and management is based on clinical signs and standard investigations. Staff should wear standard universal precaution attire for examining and treating patients; nosocomial poisoning is rare. Management of poisonings should include careful airway intervention and administration of oxygen, except in suspected paraquat poisoning. Organophosphorus insecticide poisoning causes a cholinergic crisis with excess airway secretions and acute respiratory failure. Patients should be treated with intravenous atropine and observed for the neuromuscular disorder ‘intermediate syndrome’, which can cause further paralysis and respiratory failure after 24 hours. Few antidotes exist for other agricultural chemical poisonings with the mainstay of treatment being supportive standard ICU care.
Management of radiation poisoning
Authors: Choon Francis Chin Kuok , Haur Phua Dong
Published: April 2016

In radiation poisoning, a distinction between exposure and contamination should be made. Decontamination by removing clothes, washing of skin, and removal of debris can remove up to 90% of external contaminated radiation. Treatment of acute life-threatening injuries takes priority over treatment of radiation poisoning. Triage of severely exposed patients can give an indication of dose and severity of the radiation dose absorbed. Survival is related to dose absorbed. Identification of the radiation source should be made by the radiation characteristics to determine the shielding necessary for protection of hospital staff and the antidote required. Early gastric lavage and specific antidotes for ingested radiation poisoning should be used with caution. Death is mainly due to infection and haemorrhage. Acute radiation syndrome (ARS) is a manifestation of haematopoietic, gastrointestinal, cardiovascular, central nervous system, and cutaneous syndromes. Those receiving whole body doses of 1–5 Gy may recover easily with appropriate medical management; those with doses of 6–10 Gy may survive with intensive management; and those with doses of >10 Gy seldom survive. Treatment of ARS is supportive with the use of antibiotics, colony-stimulating factors, blood products, and stem cell transplants. Protection of the staff is by reducing time exposed, increasing distance from source and proper shielding. Psychological counselling should be available to patient or staff if required.
A systematic approach to the injured patient
Authors: Burlew Clay Cothren , Moore Ernest E.
Published: April 2016

Trauma remains the most common cause of death for all individuals between the ages of 1 and 44 years, and is the third most common cause of death regardless of age. It is also the leading cause of years of productive life lost. However, death rate underestimates the magnitude of the societal toll. Organized trauma systems have improved mortality by providing timely and expert care to severely-injured patients. Patient management consists of rapid primary survey, which should focus on the identification and simultaneous treatment of immediately life-threatening injuries. A classical ABC (airway, breathing, circulation) approach is recommended and is best carried out by a trained and practiced trauma team. The primary survey is followed by a more detailed examination, the secondary survey, which consists of a head-to-toe examination to identify all specific injuries. The secondary survey should be followed by investigation and definitive care.
Pathophysiology and management of thoracic injury
Authors: Bauzá Graciela , Nubi Ayodeji
Published: April 2016

Mechanism, patient presentation, and physical exam are key elements to accurate and prompt diagnosis of thoracic injury. A high proportion of poly-trauma victims suffer thoracic injury which is associated with mortality of with 25-50%. Initial management is guided by ATLS principles of Airway, Breathing, and Circulation. The FAST (focused assessment with sonography for trauma) exam plays a key role in the initial evaluation of thoracic trauma. Most injuries to the thoracic cavity may be managed non-operatively or with bedside procedures with the caveat that patients with thoracic injury require close attention and monitoring in the ICU for potential deterioration. A high index of suspicion is paramount to successful patient care. When operative intervention is required it is often emergent.
Pathophysiology and management of abdominal injury
Authors: Johnson Steven B.
Published: April 2016

Abdominal injuries are common following blunt and penetrating trauma. They can result in a spectrum of severity from benign to potentially life-threatening conditions. Soon after injury, haemorrhage is the predominant concern, and leading cause of morbidity and mortality. Active haemorrhage resulting in shock requires emergent operative intervention and aggressive haemostatic resuscitation. However haemodynamically-stable patients benefit from non-operative management of solid organ injuries with or without angiographic embolization. Sepsis usually occurs as a result of intra-abdominal infections from missed bowel perforations or anastomotic leaks. Sterile systemic hyperinflammatory conditions can result from major hepatic necrosis or pancreatic injuries, and closely mimic infectious conditions. Damage control surgery is a valuable adjunct to the operative management of major abdominal trauma. This concept recognizes that the time and procedures required to perform definitive operative repair may be detrimental when physiological derangements are excessive. By limiting operations to controlling haemorrhage and enteric contamination, further deterioration, and the ‘vicious bloody cycle of trauma’ can be avoided. The operative and critical care management of patients with abdominal trauma should be closely integrated to correct physiological derangements with rapid stabilization and reversal of hypoperfusion. Abdominal compartment syndrome, characterized by intra-abdominal hypertension and resultant remote organ dysfunction, is a risk in patients undergoing high-volume fluid resuscitation. Emergent decompressive laparotomy is indicated in patients with abdominal compartment syndrome and results in rapid reversal of physiological compromise. Paramount to optimal management of abdominal injuries is the close integration of operative and critical care approaches.
Assessment and management of combat trauma
Authors: Aberle Sara J. , Jenkins Donald H.
Published: April 2016

Lessons from the management of combat trauma are applicable in both the military and civilian sectors. While there are additional challenges in the combat arena, preparing for the various injury patterns commonly encountered from combat-related injury and their management is imperative for medical personnel deployed to a combat zone. Combat-related mortality continues to show haemorrhage as a major cause of death, with most deaths occurring prior to arrival at a medical treatment. For fatalities that are judged to be potentially survivable, missed or delayed life-saving interventions, delayed evacuation, and inadequate haemorrhage control are all contributory factors. To target these areas, medical training and organizational efforts have been focused on improving haemorrhage control, remote resuscitation, and logistical systems. Further study should be aimed at reducing the known contributing factors and developments focused on prehospital management. Treating patients with modern resuscitative and supportive techniques is the hallmark of high-quality injury management, regardless of the mechanism of injury or the setting.
Assessment and management of ballistic trauma
Authors: Hooper Timothy , Lockey David
Published: April 2016

The severity of ballistic trauma is dependent upon multiple factors including bullet type, velocity, tissue type penetrated, and energy transfer. Patient management needs a considered approach with careful assessment, appropriate imaging and directed treatment of the wounds found. Triage, treatment and transport form the framework of effective prehospital care. In the emergency department a rapid primary survey is essential to reveal any injuries that need immediate intervention. The decision to operate and nature of surgery is determined by the patient’s suspected injuries, physiological condition and expertise available with some patients benefiting from damage control resuscitation and surgery. Indications for intensive care admission include the need for ongoing organ support, cardiovascular instability, and injuries that require close observation. Attention should be paid to cardiovascular status, coagulation, nutrition, thromboprophylaxis, infective issues, and management of specific injuries. Patients may require protracted hospital stays and extensive reconstructive surgery. The psychological and social impact of these injuries should not be underestimated.
Epidemiology and pathophysiology of traumatic brain injury
Authors: Aisiku Imoigele , Robertson Claudia S.
Published: April 2016

Although medical management of traumatic brain injury (TBI) may have improved in developed countries, TBI is still a major cause of mortality and morbidity. The demographics are skewed towards the younger patient population, and affects males more than females, but in general follow a bimodal distribution with peaks affecting young adults and the elderly. As a result, the loss of functional years is devastating. Pathology due to brain trauma is a complex two-hit phenomenon, frequently divided into ‘primary’ and ‘secondary’ injury. Hypoxia, ischaemia, and inflammation all play a role, and the importance of each component varies between patients and in an individual patient over time. The initial injury may increase intracranial pressure and reduce cerebral perfusion due to the presence of mass lesions or diffuse brain swelling. Further secondary insults, such as hypotension, reduced cerebral perfusion pressure, hypoxia, or fever may exacerbate swelling and inflammation, and further compromise cerebral perfusion. Although there are currently no specific effective treatments for TBI, an improved understanding of the pathophysiology may eventually lead to treatments that will reduce mortality and improve long-term functional outcome.
Management of traumatic brain injury
Authors: Gibson Alistair A. , Andrews Peter J. D.
Published: April 2016

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide and although young male adults are at particular risk, it affects all ages. TBI often occurs in the presence of significant extracranial injuries and immediate management focuses on the ABCs—airway with cervical spine control, breathing, and circulation. Best outcomes are achieved by management in centres that can offer comprehensive neurological critical care and appropriate management for extracranial injuries. If patients require transfer from an admitting hospital to a specialist centre, the transfer must be carried out by an appropriately skilled and equipped transport team. The focus of specific TBI management is on the avoidance of secondary injury to the brain. The principles of management are to avoid hypotension and hypoxia, control intracranial pressure and maintain cerebral perfusion pressure above 60 mmHg. Management of increased intracranial pressure is generally by a stepwise approach starting with sedation and analgesia, lung protective mechanical ventilation to normocarbia in a 30° head-up position, maintenance of oxygenation, and blood pressure. Additional measures include paralysis with a neuromuscular blocking agent, CSF drainage via an external ventricular drain, osmolar therapy with mannitol or hypertonic saline, and moderate hypothermia. Refractory intracranial hypertension may be treated surgically with decompressive craniectomy or medically with high dose barbiturate sedation. General supportive measures include provision of adequate nutrition preferably by the enteral route, thromboembolism prophylaxis, skin and bowel care, and management of all extracranial injuries.
Pathophysiology and assessment of burns
Authors: Paro John A. M. , Gurtner Geoffrey C.
Published: April 2016

Burn injury represents a complex clinical entity with significant associated morbidity and remains the second leading cause of trauma-related death. An understanding of the local and systemic pathophysiology of burns has led to significant improvements in mortality. Thermal insult results in coagulative necrosis of the skin and the depth or degree of injury is classified according to the skin layers involved. First-degree burns involve only epidermis and heal quickly with no scar. Second-degree burns are further classified into superficial partial thickness or deep partial thickness depending on the level of dermal involvement. Damage in a third-degree burn extends to subcutaneous fat. There is a substantial hypermetabolic response to severe burn, resulting in significant catabolism and untoward effects on the immune, gastrointestinal, and renal systems. Accurate assessment of the extent of burn injury is critical for prognosis and initiation of resuscitation. Burn size, measured in total body surface area, can be quickly estimated using the rule of nines or palmar method. A more detailed sizing system is recommended once the patient has been triaged. Appropriate diagnosis of burn depth will be important for later management. First-degree burns are erythematous and painful, like a sunburn; third-degree burns are leathery and insensate. Differentiating between second-degree burn types remains difficult. There are a number of formalized criteria during assessment that should prompt transfer to a burn centre.