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SECTION 7 Nutrition Part 7.1 Physiology 950 Part 7.2 Nutritional failure 960 PART 7.1 Physiology 201 Normal physiology of nutrition 951 Annika Reintam Blaser and Adam M. Deane 202 The metabolic and nutritional response to critical illness 956 Linda-Jayne Mottram and Gavin G. Lavery CHAPTER 201 Normal physiology of nutrition Annika Reintam Blaser and Adam M. Deane Key points ◆ Ingested carbohydrate, glycogenolysis, and gluconeogenesis are essential for function of brain and anaerobic tissues that depend on glucose as their main energy source ◆ Fat is the most energy-rich nutrient, but most of ingested lipids will be stored in adipose tissue because the oxidative capacity for lipids is low ◆ During periods of inadequate energy delivery, ingested or endogenous proteins are diverted into glucose metabolism, and this provides a rationale to deliver more protein during these periods ◆ Basic metabolic rate (BMR) is the largest component of total daily energy requirements, even in the case of very high physical activity or acute illness ◆ Daily energy requirements range from 1800 to 2800 kcal/ day or 25 to 30 kcal/kg body weight (BW)/day roughly— carbohydrates should provide 55–60%, lipids 25–30%, and proteins 10–15% Body composition Water (approximately 60% in adult males and 50% in females [1]), protein, minerals, and fat are the main components of human body Essential fat is contained in bone marrow, the heart, lungs, liver, spleen, kidneys, intestines, muscles, and central nervous system Fat located in adipose tissue is called storage fat The two-component model distinguishes between fat and fat-free mass (FFM), while the three-component model further divides FFM into body cell mass and extracellular mass [2] Lean body mass is an indirect estimation of the weight of bones, muscles, ligaments, and internal organs, which can be calculated using various equations [3] Direct methods of assessing body composition, such as skinfolds, bioelectrical impedance analysis, and hydrostatic weighing are not routinely used in the critically ill While being underweight is associated with poorer outcomes in the critically ill, obesity does not appear to be harmful (and may be beneficial) [4] Estimation of the ideal body weight [5]is often inaccurate, but the range may be useful and can be calculated (Broca’s index): (Height (cm) − 100) ± 15% for women or 10% for men [eqn 1] Clinical examination and laboratory tests General clinical examination of skin, hair, eyes, gums, tongue, bones, muscles, and thyroid gland tends only to reveal signs in cases of marked malnutrition or vitamin/mineral deficiencies Laboratory tests such as blood haemoglobin, total lymphocyte count, glucose, serum albumin, prealbumin, transferrin, total protein measurements, and calculation of nitrogen balance have limitations, but have been used Nitrogen balance is considered the most dynamic nutritional indicator Essential nutrients: substrate and energy metabolism Essential nutrients are substances that are not synthesized (or are synthesized in too small amounts) within the body and must, therefore, be ingested or administered They include essential fatty acids, essential amino acids, vitamins, and dietary minerals Energy Energy is derived from three major categories of macronutrient— protein, carbohydrate, and lipids—and is released by breaking down carbon–carbon bonds created in plants via photosynthesis Energy requirements to maintain stable weight can be estimated, using calculations or measured using calorimetry Oxidative (burning for energy) and non-oxidative (storage, synthesis) substrate metabolism occur to a different extent according to the type of macronutrient and state of energy stores [2] Respiratory quotient (RQ) is used to describe oxidative substrate metabolism Estimation of nutritional status Carbohydrates Body mass index (BMI) = weight (kg)/height (m) and provides a rough estimation of nutritional status [2] A limitation of BMI is that the calculation does not distinguish between muscle and fat mass A BMI of 18.5–24.9 kg/m2 is considered ‘normal’ regardless of age or population [1] BMI has a U-shape relation to morbidity and mortality [2] In persons >60 years old being slightly heavier (BMI 26–27) is associated with the longer life expectancy [2] Carbohydrates are compounds comprised of carbon, hydrogen, and oxygen Depending on the composition of these molecules, carbohydrates are divided into mono-, di-, oligo-, and polysaccharides While carbohydrates are non-essential nutrients, they comprise a substantial proportion of calories (4.1 kcal/g) in a normal diet [1] In plants, carbohydrate is stored as starch, whereas in animals it is stored as glycogen Table 201.1 Nutritional requirements in adults Nutrient Role Daily needs Deficiency Abnormalities in ICU Macronutrients Energy, structure, all functions No absolute daily requirements exist Starvation Carbohydrates Major energy source, energy storage and transport, structure 55–60% of calories, max g/kg BW at rest Hypoglycaemia, ketoacidosis Hyperglycaemia (insulin resistance, counter-regulatory hormones) Lipids Energy storage, cell membrane structure, signalling molecules 25–30% of calories Malabsorption of fat-soluble vitamins Hyperlipidaemia with excessive parenteral nutrition and propofol Proteins Enzymes, structure, signalling, immune response 10–15% of calories 0.8 g/kg BW Kwashiorkor, cachexia Protein energy wasting occurs frequently Vitamin Role RDA Deficiency In ICU A (retinol) Retinal pigment Male 1000 µg female 800 µg Night blindness, follicular hyperkeratosis B1 (thiamine) Coenzyme in decarboxylation of pyruvate and alpha-keto acids Male 1.5 mg, female 1.1 mg Beriberi, Wernicke’s encephalopathy Threshold for thiamine administration should be low B2 (riboflavin) Coenzyme for oxidative enzymes Male 1.7 mg, female 1.3 mg Mouth ulcers, normocytic anaemia B3 (niacin) also vitamin PP or nicotinic acid Coenzyme, precursor for NAD and NADP Male 19 mg, female 15 mg Pellagra, neurological symptoms B6 (pyridoxine) Coenzyme in synthesis of amino acids, haeme, neurotransmitters Male 2.0 mg, female 1.6 mg Muscle weakness, depression, anaemia B12 (cobalamin) coenzyme (deoxyribonucleotids), formation of erythrocytes, myelin µg Neurological symptoms With pernicious anaemia (lack of intrinsic factor) C (ascorbic acid) Cofactor in collagen synthesis 60 mg Scurvy Antioxidant effect, cave oxalosis D (1,25-cholecalciferol) Ca2+ absorption and metabolism 5–10 µg Rickets E (alpha-tocopherol) Antioxidant Male 10 mg, female mg Peripheral neuropathy Antioxidant effect K Clotting, synthesis of prothrombin, factors VII,IX,X Male 70–80 µg female 60–65 µg Coagulopathy Biotin (also vitamin B7 or H, or coenzyme R) Cofactor for several carboxylase enzymes; cell growth 30–100 µg Neurological symptoms, alopecia, conjunctivitis, dermatitis Folate (vitamin B9) Necessary for synthesis of DNA, haemopoesis Male 200 µg female 180 µg (pregnancy 400) Megaloblastic anaemia, peripheral neuropathy, neural tube defects Panthothenic acid (vitamin B5) Synthesis of CoA Carbohydrate, and fat metabolism 4–7 mg Gastrointestinal and neurological symptoms Mineral Role RDA Deficiency In ICU Calcium Bone, intracellular signalling 800–1200 mg Osteoporosis, arrhythmia hypertension Chromium Cofactor 50–200 µg Impaired glucose tolerance, peripheral neuropathy Deficiency reported during long-term parenteral nutrition Copper Cofactor (oxidative phosphorylation, neurotransmitter synthesis etc.) 1.5–3 mg Myelodysplasia, anaemia, leucopenia, neurological symptoms Deficiency after gastric bypass Reduce replacement in liver failure Iron Haemoglobin and cytochromes Male 10 mg, female 15 mg Microcytic anaemia, mucosal atrophy (continued) Chapter 201 normal physiology of nutrition Table 201.1 Continued Nutrient Role Daily needs Deficiency Abnormalities in ICU Iodine Thyroid hormones 150 µg Goitre, hypothyroidism Magnesium Complex with ATP Male 350 mg, female 280 mg Muscle weakness, GI, and cardiac symptoms Deficiency common and associated with major adverse outcomes Manganese Antioxidant 2–5 mg Reduces replacement in liver failure Molybdenum Cofactor 75–250 µg Liver dysfunction Phosphorus Major component of the skeleton, nucleic acids, and ATP 800–1000 mg Potentially catastrophic reduction during refeeding syndrome Potassium Membrane potential At least 3510 mg (conditional recommendation by WHO) Arrhythmias Often life-threatening hyper- or hypo-K, narrow therapeutic/normal range Selenium Antioxidant Male 70 µg, female 55 µg Cardiomyopathy Antioxidant effect Zinc Antioxidant, cofactor Male 15 mg, female 12 mg Skin lesions, loss of appetite Antioxidant effect RDA, Recommended daily allowance Adapted from a table published in Medical Physiology, Second Edition, Boron WF and Boulpaep EL, Copyright Elsevier 2012 As an energy source, glucose is oxidized to CO2 and water: C 6H12O6 + 6O2 + 32ADP + 32P − > CO2 + 6H2O ( + 32ATP + heat RQ = 6CO2 / 6O2 = 1.0 ) [eqn 2] At rest, the maximum oxidative capacity is approximately g glucose/ kg BW/day [2] If the glucose intake is greater non-oxidative metabolism occurs, resulting in glycogenesis (glycogen store is limited to 200–500 g; storing consumes about 6% of energy stored in glucose) and, after reaching the limit, in lipogenesis (storing costs 23% of energy) [6] As an isolated energy source blood glucose covers energy needs for about 30 minutes, whereas glycogen would last for approximately one day [2] Glycogen is stored in hydrated form, making it less energy-efficient, but easily available Hepatic or muscle glycogenolysis occurs rapidly in response to hypoglycaemia or anaerobic demands Gluconeogenesis is the synthesis of glucose from non-hexose precursors (lactate, pyruvate, intermediates of the citric acid cycle, 18 of 20 amino acids and glycerol) [1] Leucin and lysine together with fatty acids are not gluconeogenic, but ketogenic Their breakdown-product is acetyl coenzyme A (CoA), which cannot generate pyruvate or oxalo-acetate Gluconeogenesis is essential for the brain and anaerobic tissues (blood cells, bone marrow, renal medulla) that depend on glucose as their main energy source [1], but is energy-expensive, consuming 24% of energy contained in amino acids (AA) [6] Lipids Lipids are hydrophobic compounds that are soluble in organic solvents such as acetone Lipids contain 9.4 kcal/g of energy and can be ingested as triglycerides, sterol esters or phospholipids [1] To generate energy, fatty acids are oxidized to CO2 and water C15H31COOH ( palmitic acid ) + 23O2 + 106ADP + 106P −> 16CO2 + 16H2O ( + 106ATP + heat RQ = 16CO2 /23O2 = 0.70 ) [eqn 3] In resting humans the oxidative capacity for lipids is 0.7 g/kg BW/ day [2] Greater amounts of ingested lipid will be stored as triglycerides in fat tissue Fat constitutes approximately 20% of body weight, and the standard triglyceride store has the capacity to cover the body’s energy requirements for about 2 months Ketone bodies are produced when accelerated oxidation of fatty acids leads to incomplete breakdown, producing acetyl CoA faster than the citric acid cycle can utilize it [1] Ketone bodies (acetoacetate, β-hydroxybutyrate, and acetone) may serve as an alternative energy resource, e.g during starvation up to 50% of brain energy demands might be met via ketone bodies [2] Protein Nitrogen differentiates protein from carbohydrates and fats The major source of endogenous protein is muscle, which is converted into energy via complex metabolic pathways When AA, either endogenous proteins or ingested, are metabolized to CO2 and water, 4.3 kcal/g of energy can be released [1] Protein metabolism in cells additionally results in the production of energy-containing metabolites (urea, ureic acid, and creatinine) The RQ for protein oxidation is 0.80–0.85 [1] Protein stores are about 14% of body weight, but only half of it is available as an energy source, lasting for 10 days approximately In health, protein catabolism contributes less than 5% of energy requirements, but this increases to 15% during starvation The body constantly breaks down proteins to AAs and synthesizes other proteins according to the current needs of the body (protein turnover) Nine out of 20 AAs are essential—the body cannot synthesize them at sufficient rates for long-term survival and they must be ingested to replace the proteins oxidized during daily turnover Excess protein is converted to glycogen or triacylglycerols [1] To maintain nitrogen balance in an average adult individual, ingestion of 0.6–0.8 g/kg BW/day of protein is needed [2] However, during periods of inadequate energy delivery greater amounts of protein are diverted into glucose metabolism and, in catabolic states, there is a marked increase in endogenous protein breakdown Accordingly, more protein either ingested or administered may be beneficial during these periods [7] 953 954 Section 7 nutrition: physiology Nitrogen (N) balance is the sum of protein degradation and protein synthesis, reflecting the changes in protein stores where: N Balance = N int ake − N losses, N intake = protein intake ( g/day ) /6.25, and N losses = urinary urea N ( UUN ) , g/day, determined from a 24-hour urine collection) + g miscellaneous other N losses from skin, mucosa and with faeces [eqn 4] N balance is used to estimate current protein requirements Positive or negative N balances indicate anabolic or catabolic states respectively As in patients with renal replacement therapy (RRT) measurement of UUN is not applicable; the total nitrogen appearance (TNA) is used to express nitrogen losses [8]: urea nitrogen loss + TNA in a patient with RRT = oss during RRT ( g ) AA nitrogen lo change in interdialytic blood urea + × nitrogen BUN g/L total body water L ( )( ) ( ) [eqn 5] Protein energy wasting [9]due to inadequate protein intake and high catabolism is thought to occur frequently in the critically ill While preventing or limiting protein deficiency in this group is often proposed as beneficial, it is not yet established that such an approach improves outcomes Other Other essential nutrients include inorganic elements like calcium, potassium, iodine, iron, trace elements (dietary minerals that are needed in very small quantities) and vitamins, which are necessary for normal functioning of the body The role, recommended daily allowances and signs of deficiency of these essential vitamins and minerals are presented in Table 201.1 Vitamins Vitamins are divided into water-soluble (B,C) and fat-soluble (A, D, E and K) groups Bonds between fat-soluble vitamins with proteins are broken by the acidity of gastric juice and proteolysis Assimilation of fat-soluble vitamins relies on lipid absorption and their deficiency occurs in various fat malabsorption states Thiamine (B1) with its phosphorylated derivatives plays a fundamental role in energy metabolism and is used in the biosynthesis of the neurotransmitters Its best-characterized derivate thiamine pyrophosphate is a coenzyme in the catabolism of sugars and amino acids Thiamine derivatives and thiamine-dependent enzymes are present in all cells of the body, but the nervous system and the heart are particularly sensitive to its deficiency Thiamine deficiency may occur because of concomitant chronic disease or alcoholism and can lead to severe neurological impairment and contribute to increased mortality [10] Vitamin K is pivotal for synthesis of coagulation factors VII, IX, X, protein C and protein S in liver, acting as a co-factor for carboxylation Its deficiency occurs with fat malabsorption, but also during severe bleeding (disseminated intravascular coagulation) Previous treatment with vitamin K antagonists, blocking carboxylation of prothrombin (factor II), factors VII, IX and X, and making their complexes with Ca2+ and therefore usage for coagulation impossible, is common in hospitalized patients Supplementation of vitamins E and C has been proposed as having beneficial antioxidant effects in the critically ill [11] This has yet to be established and particularly in patients with renal failure excessive vitamin C may lead to oxalosis Minerals Calcium is necessary for the structure (calcium phosphate in bones), signalling, and enzymatic processes (co-enzyme for clotting factors, pre-synaptic release of acetylcholine) in the body Magnesium is essential for energy in every cell type in organism, as ATP, the main source of energy in cells, must be bound to a magnesium ion in order to be biologically active Supplementation of minerals such as selenium and zinc has been described in the critically ill and warrants further study [12] Next to the essential nutrients food includes fibres and other ballast substances, carotinoides, bioflavonoids etc considered important for health, but their functions are clarified incompletely Energy consumption Estimation of energy consumption Basal metabolic rate (BMR) is an estimation of metabolism, measured under standardized conditions in the absence of stimulation Resting metabolic rate (RMR) is measured during less strict conditions and is therefore higher than BMR [1] BMR and RMR are measured by gas analysis through either direct (the body is positioned in a chamber to measure the body’s heat production) or indirect (CO2 production is measured) calorimetry [13] BMR can be estimated by a number of calculations of Basal Energy Expenditure (BEE) with Harris-Benedict equation being the most frequently used in critical care: Adult males: ( ) ) [eqn 6] ) ( ) BEE ( kcal/day ) = 13.8 × weight in kg ( + × height in cm − (6.8 x age ) + 66.5 Adult females: ( BEE ( kcal/day ) = 9.6 × weight in kg + 1.8 × height in cm − 4.7 × age + 655 [eqn 7] ( ) As body weight is the major factor that determines BEE, a simplified estimate of 25 kcal/kg BW/day is often used and our experience is that the latter approach is adequate for clinical purposes The BMR is the largest component of total daily energy requirements, even in case of very high physical activity, as well as in the most hypermetabolic patients The various estimations of stress/ activity factors available to calculate the total energy expenditure (TEnE = BEE × stress/activity factor) tend to overestimate the TEnE in ICU patients, as measured TEnE is often close to calculated BEE [6] Chapter 201 References Boron WF and Boulpaep EL (2012) Medical Physiology, 2nd edn Philadelphia: Saunders Speckmann EJ, Hescheler J, Köhling R (2008) Physiologie, 5th edn Munich: Elsevier R Hume (1966) Prediction of lean body mass from height and weight Journal of Clinical Pathology, 19, 389–91 Heyland DK, Dhaliwal R, Jiang X, and Day AG (2011) Identifying critically ill patients who benefit the most from nutrition therapy: the development and initial validation of a novel risk assessment tool Critical Care, 15, R268 Pai MP and Paloucek FP (2000) The origin of the ‘ideal’ body weight equations Annals of Pharmacotherapy, 34, 1066–9 Fontaine E and Müller MJ (2011) Adaptive alterations in metabolism: practical consequences on energy requirements in the severely ill patient Current Opinion in Clinical Nutrition and Metabolic Care, 14, 171–5 Shils ME, Shike M, Ross AC, Caballer B, and Cousins RJ (2006) Modern Nutrition in Health and Disease, 10th edn London: Lippincott Williams & Wilkins normal physiology of nutrition Chua HR, Baldwin I, Fealy N, Naka T, and Bellomo R (2012) Amino acid balance with extended daily diafiltration in acute kidney injury Blood Purification, 33, 292–9 Kopple JD (1999) Pathophysiology of protein-energy wasting in chronic renal failure Journal of Nutrition, 129(1 Suppl.), 247S–51S 10 Berger MM, Shenkin A, Revelly JP, et al (2004) Copper, selenium, zinc, and thiamine balances during continuous venovenous hemodiafiltration in critically ill patients American Journal of Clinical Nutrition, 80, 410–16 11 Casaer MP, Mesotten D, and Schetz MRC (2008) Bench-to-bedside review: Metabolism and nutrition Critical Care, 12, 222 12 Andrews PJ, Avenell A, Noble DW, et al (2011) Randomised trial of glutamine, selenium, or both, to supplement parenteral nutrition for critically ill patients; Scottish Intensive care Glutamine or selenium Evaluative Trial Trials Group British Medical Journal, 342, d1542 13 Singer P, Anbar R, Cohen J, et al (2011) The tight calorie control study (TICACOS): a prospective, randomized, controlled pilot study of nutritional support in critically ill patients Intensive Care Medicine, 37, 601–9 955 CHAPTER 202 The metabolic and nutritional response to critical illness Linda-Jayne Mottram and Gavin G. Lavery Key points ◆ The metabolic response to critical illness is biphasic, the acute stage being accompanied by increased hypothalamic pituitary function and peripheral resistance to effector hormones ◆ The acute phase has been considered adaptive, increasing the availability of glucose, free fatty acids, and amino acids as substrates for vital organs ◆ Prolonged critical illness results in damped hypothalamic responses that are implicated in the critical illness wasting syndrome ◆ Cytokines can stimulate the hypothalamic pituitary axis directly as part of the stress response in critical illness ◆ Gastrointestinal failure may in part be a neuroendocrine phenomenon, with disordered hormonal and enteric nervous system responses Introduction The metabolic response to critical illness is complex and affects every body system The response to acute critical illness differs from the response to more prolonged states These differences or the dynamic complexity of the neuroendocrine changes themselves, may explain the failure of pharmacological manipulation to date The gut response to critical illness is also an example of neuro endocrine derangement The interaction between body systems becomes apparent when gastrointestinal failure and inadequate nutrition combine to exacerbate the catabolic state Ultimately, the consequence is to lengthen the illness, prolong intensive care stay, and hamper the recovery process The somatotrophic axis Normal physiology Human growth hormone (GH) is produced in the somatotrophic cells of the anterior pituitary in response to hypoglycaemia, exercise, sleep, high protein intake, and acute stress This process is regulated by the stimulatory effect of growth hormone releasing hormone (GHRH) from the hypothalamus and also by the hunger-stimulating hormone, ghrelin Inhibitory effects on GH release occur via somatostatin secretion from the hypothalamus GH acts directly on the tissues causing lipolysis, anti-insulin effects, sodium and water retention, and immunomodulation It also acts indirectly via hepatic production of insulin-like growth factor (IGF-1) to bring about protein synthesis and thus protect lean body mass Acute critical illness Serum GH levels are elevated overall and demonstrate increased pulsatility However, IGF-1 levels are lower and GH receptor expression is reduced, which together produce a state of peripheral GH resistance Energy-consuming anabolic processes are halted, permitting the release of amino acids for use as an energy substrate The direct effects of lipid breakdown and antagonism of insulin are permitted, which again favourably releases energy reserves in the acute phase of critical illness [1] Prolonged critical illness Levels of GH are reduced with a more erratic and less pulsatile pattern of secretion, a process that is compounded by low ghrelin levels Despite less peripheral resistance to GH, a state of relative deficiency persists and contributes to critical illness wasting [2] The return of peripheral responsiveness to GH was thought to provide a therapeutic target for exogenous GH administration, but actually results in higher morbidity and mortality These findings may be a function of timing of GH administration and remain under investigation Greater abnormalities are seen in the male GH axis, which has been theorized to account for some gender differences in ICU outcome The thyrotropic axis Normal physiology In health, thyrotropin-releasing hormone (TRH) is released from the hypothalamus and in turn the anterior pituitary secretes thyroid-stimulating hormone (TSH), with negative feedback via the thyroid hormones triiodothyronine (T3) and thyroxine (T4) Acute critical illness The adaptive response of the thyroid to critical illness is an energy conservation strategy, reducing expenditure on metabolic processes It is often called ‘non-thyroidal illness syndrome’, but may also be known as ‘low T3 syndrome’ or ‘sick euthyroid syndrome’ Laboratory parameters include low serum T3 levels, increased reverse T, while TSH and free T4 remain largely normal [3] Low T3 levels are partly due to reduced peripheral conversion from T4 The enzyme 5’-monodeiodinase catalyses this peripheral Chapter 202 conversion and accounts for 80% of free T3 in the circulation This enzyme is inhibited during the stress response and in particular by glucocorticoids It contains the novel amino acid selenocysteine and so may be affected by selenium deficiency Prolonged critical illness As the illness progresses, free T4 decreases and is a reflection of illness severity Those with the lowest T3 and T4 levels in critical care have the highest mortality [4] There is dampening of the normal negative feedback loop TSH fails to increase and loses its pulsatile secretion pattern, only doing so as the patient starts to recover Non-thyroidal illness syndrome is associated with prolongation of mechanical ventilation in the ICU population [5] Despite the biological rationale for treating such a state of continued relative hypothyroidism, there is little convincing proof of efficacy Others [6] have argued for treatment with hypothalamic releasing peptides, rather than thyroid hormone per se, but again definitive evidence to support this strategy is lacking The adrenocortictrophic axis In health, corticotrophin-releasing hormone (CRH) from the paraventricular nucleus is carried in the hypophyseal-portal tract and stimulates release of adrenocorticotrophic hormone (ATCH) Cortisol is produced in the zona fasiculata of the adrenal cortex and a negative feedback loop exists to regulate secretion and synthesis Acute critical illness Plasma ACTH and cortisol levels increase with loss of the normal circadian rhythm The hypothalamus is stimulated by a direct effect of cytokines The typical effects of glucocorticoids are manifest in order to maintain homeostasis after the stressful insult These include use of alternative energy strategies, such as mobilization of amino acids from extrahepatic tissues, lipolysis, and subsequent utilization of glycerol, and gluconeogenesis in the liver They have a regulatory role in the acute inflammatory response, by blocking cytokine gene expression and up-regulating specific anti-inflammatory processes The cardiovascular effects of glucocorticoids include the maintenance of vascular responsiveness to catecholamines, endothelial integrity, and intravascular volume via their mineralocorticoid actions [7] These anti-inflammatory and vascular effects explain the biological rationale for the use of low-dose corticosteroids in septic shock [8] Prolonged critical illness When critical illness is protracted, plasma cortisol levels remain high, but ACTH decreases It is likely that this effect is mediated via peripheral mechanisms, such as substance P, atrial natriuretic peptide, endothelin, and cytokines The adverse effects of sustained hypercortisolism, such as muscle wasting, hyperglycaemia, hypokalaemia, poor wound healing, and psychiatric sequelae become apparent and can be seen as a maladaptive response [9,10] Sex hormones and prolactin In health gonadotrophin-releasing hormone (GNRH) is secreted in a pulsatile pattern and stimulates the anterior pituitary to release luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the gonadotroph cells In males, LH drives testosterone production in the Leydig cells of the testes metabolic and nutritional response In the acute phase of critical illness, serum testosterone levels are low (in spite of elevated LH levels) and prolactin is high Low testosterone switches off the anabolic processes that maintain skeletal muscle mass High oestradiol levels are found—an adaptation that was originally thought to be beneficial as oestrogens inhibit proinflammatory cytokine production Recent findings appear to contradict this and there is an association with increased mortality [11] In prolonged critical illness there is a state of hypogonadal hypogonadism and prolactin deficiency T- and B-lymphocytes possess prolactin receptors, requiring it for their function Hypoprolactinaemia may play a role in the immune paralysis seen in illnesses of longer duration The use of exogenous dopamine could theoretically suppress prolactin secretion and negatively impact immune function Despite these concerns and a higher incidence of adverse events in shocked patients treated with dopamine, the evidence falls short of it having an adverse impact on mortality [12] The role of the autonomic nervous system The classical ‘fight or flight’ response is mediated via adrenaline and noradrenaline A variety of physiological insults, such as pain, hypotension, hypoxia, acidosis, and hypercarbia can stimulate the sympathetic nervous system Pre-ganglionic sympathetic fibres terminate in the adrenal medulla and cathecholamines are released rapidly from synaptic vesicles The leukocyte itself can be an additional source of cathecholamines Cardiovascular responses occur via B1 receptors and include positive inotropy and chronotropy Stimulation of the reninangiotensoin system at the juxta-glomerular cells acts to maintain intravascular volume and tone B2 receptor activation results in gluconeogensesis and glycongenolysis B2 stimulation dampens the pro-inflammatory cytokine response and in sepsis it alters the balance of T helper cells from THC1 to THC2 Some regulation also occurs via α-receptors Alpha-1-mediated vasconstriction acts to maintain blood pressure, but reduced gut perfusion and motility are adverse consequences discussed in ‘Loss of Barrier Function’ The parasympathetic response to traumatic and infectious insults is largely anti-inflammatory and occurs through the activation of α7 nicotinic acetylcholine receptors This acetylcholine-mediated reduction in cytokine production occurs, not only from a direct effect on macrophages, but also indirectly via vagal splenic innervation Vitamin D metabolism Vitamin D deficiency is common in critical illness for two reasons: ◆ Vitamin D is lost through lack of serum binding proteins in acute illness ◆ Many chronic conditions predisposing to critical illness will reduce sunlight exposure and thus synthesis of Vitamin D in the skin The clinical consequences of Vitamin D deficiency are bone resorption, hypercalcaemic immune dysfunction, namely reduced innate responses and heightened adaptive responses, such as prolonged hypercytokinaemia [13] The role of cytokines Cytokines are intercellular messenger proteins that act on various cell types to bring about pro- and anti-inflammatory responses 957 958 Section 7 nutrition: physiology during critical illness They can have local (autocrine or paracrine) or widespread (endocrine) effects Cytokines are produced via stimulation of Toll-like receptors (TLRs), which may be a future pharmacological target At the cellular level, TLRs are activated not only by the presence of microbial proteins as part of the innate immune response, but also by non-infectious insults, such as tissue injury Here, endogenous intracellular proteins released from dying cells are the trigger, and are known as ‘alarmins’ The cell surface TLRs initiate the nuclear factor kappa-beta (NF-κβ) transcription pathway, which ultimately generates cytokine proteins Note that some cytokines can be released more readily in response to catecholamines with no requirement for gene transcription Tumour necrosis factor α (TNFα) has a positive effect on NF-κβ and is responsible for triggering further cytokine release, in what is described clinically as the ‘cytokine storm’ There are several cytokine families (Table 202.1) including the interleukins, interferons, tumour necrosis factors, chemokines, and colony-stimulating factors Burns, tissue trauma, or infection results in a cascade of pro-inflammatory cytokines, of which the key players are TNFα, IL-1, IL-6, and IL-8 Levels of these cytokines correlate with illness severity and outcome Cytokine gene polymorphisms and aberrant responses to TLR ligands are partly accountable for the individual response to sepsis and other insults However, despite the wealth of research in this area, modulation of interleukins and TNFα with recombinant pharmacological agents has not been widely successful Pathophysiology of the gastrointestinal tract in critical illness The normal functions of the gastrointestinal (GI) tract extend beyond digestion, absorption, and elimination Important immune and metabolic functions are performed by the gut, and crucially it forms a barrier between bacteria in the intestinal lumen and the sterile internal milieu The GI dysfunction associated with critical illness has been poorly defined and lacked universal terminology until recently [14] A number of clinical manifestations of GI dysfunction are recognized, including stress ulceration, gastro-oesophageal reflux, intolerance of enteral nutrition, ileus, acalculous cholecystitis, abdominal compartment syndrome, intestinal ischaemia, and gastrointestinal hypermotility The pathophysiology of these well recognized clinical phenomena can be explained by the complex interplay between the epithelium, commensal bacteria, and the mucosal immune system [15] The gut has been described as the ‘motor’ of multi-organ dysfunction syndrome and a number of key factors in its response to critical illness reinforce that status as a driver of systemic inflammation Loss of barrier function Table 202.1 Effects of cytokines in the inflammatory process Cytokine Effects TNFα ◆ Rises early in response to sepsis and trauma Activates HPA axis ◆ Induces fever and increases insulin resistance ◆ Major trigger for other cytokine release (IL-1 and IL-6) ◆ Promotes phagocytosis and neutrophil chemotaxis ◆ IL-1 ◆ Fever ◆ ◆ IL-6 ◆ ◆ T cell activation and B cell proliferation Activates HPA axis and suppresses anabolic activity Major activator of acute phase protein synthesis B and T cell differentiation IL-8 Neutrophil chemotaxis and activation HMGB1 ◆ Macrophage migration inhibitory factor (MIF) ◆ Multiple effects including acting as an alarmin and cytokine ◆ Can be induced via NF-κβ and cell death ◆ Therefore, an initiator and effector of the inflammatory response ◆ Role in vascular endothelium and enterocyte permeability Key link between immune and endocrine system Expressed by leucocytes and stored intracellularly unlike other cytokines ◆ Secreted by HPA axis in response to stress or infection ◆ Antagonizes the immunosuppressive actions of endogenous steroids ◆ Although perfusion of the gut is autoregulated, the gastrointestinal epithelium is predisposed to ischaemia for anatomical reasons Macroscopically, endogenous cathecholamines acting on alpha-receptors constrict the splanchic circulation Arginine vasopressin and angiotensin also contribute to this non-occlusive ischaemia The small bowel is particularly prone to this Microscopically, the mucosa at the tips of the villi are most at risk of hypoxia A countercurrent blood supply to the metabolically active villus via a central arteriole and network of venules renders it extremely supply dependent The damaged enterocytes slough off and permit translocation of endotoxins and bacteria In addition, ischaemia-reperfusion injury and oxidant stress are likely to further exacerbate mucosal injury Even in the absence of epithelial cell death, the barrier function of the intestine can be lost through disruption of cellular tight junctions This paracellular route is another way in which endotoxin and bacteria may enter the circulation or lymphactics, resulting in sepsis or the systemic inflammatory response syndrome Cytokines are likely to be responsible, with IL-4, interferon-gamma and HMGB-1 being implicated Alteration of gut microflora in critical illness can also compromise intestinal barrier function [16] This shift from commensal bacteria to pathogenic strains can occur as a result of antibiotic use, acid suppression or the illness itself It is likely that commensal Gram-negative anaerobes provide protection to the mucosa through promotion of mucosal repair, increased mucus production and the induction of selective bactericidal proteins, which preferentially target Gram-positive pathogens In the stomach, stress ulceration may be regarded as loss of barrier function and classically affects the gastric fundus Reduced mucosal prostaglandin synthesis and lower secretion of bicarbonate-rich 1890 index hydroxymethylglutaryl-coenzyme A reductase inhibitors, see statins hyoscine 854 hyperadrenalism 1244 hyperaldosteronism 1196 hyperbaric oxygen 141 carbon monoxide poisoning 1561–3 decompression illness 1679, 1680–1 hyperbilirubinaemia 907, 912, 941 hypercalcaemia 1204 hypercapnia 394–7 circulatory response 524–6 oxygen therapy 142 permissive 393, 395 physiological causes 342–4 respiratory acidosis 524 hyperchloraemic acidosis 1213, 1218 hypercholesterolaemia 676 hyperglycaemia 218 critical illness polyneuropathy 1828 diabetic emergencies 1234–8 pathophysiology 1226–7 stress 1226–7 subarachnoid haemorrhage 1135 see also blood glucose control hyperglycaemic hyperosmolar state 1234–8 hyperinflation 352 dynamic 386, 506–9, 513–14 hyperkalaemia 1193–5 hyperlactataemia 639, 644–5, 646 hypermetabolism 1654, 1660 hypernatraemia 1189–90, 1770 hyperoxaemia 139 hyperoxia 1095 hyperperfusion syndrome 1773 hyperphosphataemia 1207–8, 1209 hypersensitivity reactions 1498, 1499 hypertension 762–70 coronary artery disease 676 diabetes 765 emergence 1769 emergencies 153 genetics 765 hypercoagulability 765 induced 1134–5 JNC-8 guidelines 769–70 management 153, 155, 258, 767–70 pathophysiology and causes 763–6 post-neurosurgery 1769 pregnancy 153, 765, 1750–2 resistant 766 stroke 1113–14, 1119 hyperthermia 1686–9 malignant 1772–3, 1775, 1687 MDMA poisoning 1537 hyperthermic crises 1172–5 hyperthyroidism 1251, 1252 hypertonic crystalloids 309 hypertonic saline 1191, 1638 hyperviscosity syndromes 1278 hypocalcaemia 1203–4 hypocapnia 527–8 hypoglycaemia 218, 1227–8 autonomic failure 1238 diabetes 1235, 1238 insulin-therapy associated 221 hypokalaemia 1195–6 hypomagnesaemia 1199 hyponatraemia 1135, 1189, 1190–1, 1770 hypophosphataemia 1206–7, 1208–9 hypopituitarism 216, 1246, 1247 hypotension 695–703, 1769 orthostatic 1530 hypothalamic-pituitary-adrenal axis 241 hypothalamic-pituitary-endocrine axis 1183–4, 1184 hypothalamus 1183 immune regulation 1483 hypothermia accidental 1684, 1690–2 post-cardiac arrest 286, 295–6 therapeutic 286, 295–6, 1093–5,1474–5, 1638 hypothyroidism 1253 hypotonic crystalloids 309 hypoventilation 343, 389 hypovolaemia 249, 611–12 hypovolaemic shock 696–7, 702 hypoxaemia 389–93 physiological causes 342–4 respiratory acidosis 524 hypoxia haemorrhage and 1459 host response 1459–61 pulmonary vasoconstriction 323 hypoxia-inducible factor-1 1459–60 hypoxia-responsive element 1460 I ibuprofen 191, 1490–1 ibutilide 167 ICU-acquired weakness 1176–9, 1812, 1828, 1849 ICU diaries 1846, 1847 ICU nurse 1863 ideal body weight 951 I:E ratio 431 ifosamide 1803, 1804 i-gel® 264 IL-1 receptor antagonist 1489–90 ILA active™ 482 ileus 856–7 iloprost 796 imaging abdomen 820–5 acute acalculous cholecystitis 886, 887 aortic dissection 691–2 brain 1063–5 cardiovascular system 662–7 central nervous system 1063–5 endocarditis 663, 664, 749–51 hypoxaemia 390 ischaemic stroke 1117–18 meningitis 1141 microcirculation 643, 659–60 pancreatitis 822, 896, 898–899 pneumothorax 575–6 respiratory system 321–2, 355–60 sepsis 1410 spinal cord injury 1151, 1642 spinal trauma 1065 subarachnoid haemorrhage 1064–5, 1127–30 traumatic brain injury 1063, 1631–2, 1634 upper airway obstruction 365 urinary tract 992–6 visceral perforation 873 imidazoles 240 imipenem/cilastatin 236, 238 imipramine 194, 1531 immune-enhancing feeds 974–5, 978 immune reconstitution syndrome 1390–1 immune system abdominal organ transplantation 1778, 1779 adaptive immunity 1485–7, 1493–4 autonomic regulation 1482–4 burns 1654 cardiac transplantation 1783–4 drug-induced depression 1383–7 gastrointestinal system and 812 hypercapnia 395 immunomodulation 1488–91 immunoparesis 1493–5 innate immunity 1427–30, 1450–2, 1473, 1493 lung transplantation 1787 pre-eclampsia 1749 shock 701–2 sleep disturbances 1070 immune thrombocytopenia 1278, 1297 immunocompromised patients continuous positive airway pressure 408 infection 1382–94 non-invasive ventilation 412 immunonutrition 974–5, 978 immunosuppressive agents 1384–7, 1779 immunotherapy 244–6 impact analysis 35 impedance threshold device 278 Impella CardioSystem® AG 716 implantable cardiac devices 1671 implementation rapid response systems 12 telemedicine 52–3 implied consent 111 improvised explosive devices 1612, 1618 INARC score 121, 122, 123 incendiaries 1618 incentive spirometry 561, 562 incremental cost-effectiveness ratio 94 indirect calorimetry 969–72 indocyanine green 827, 829, 909, 922, 923 induced hypothermia 286, 295–6, 1093–5, 1474–5, 1638 indwelling pleural catheters 582 infection abdominal organ transplantation 1776 acute acalculous cholecystitis 886 acute liver failure 916 acute on chronic liver failure 941, 944 ballistic injury 1618 biomarkers 1348–50 bone marrow transplantation 1797–8 device-related 1374–6 diarrhoea 860–2 disseminated intravascular coagulation 1288 haematological malignancy 1791–2 health care-associated infection, see nosocomial infection host–pathogen interaction 1462–4 host response 1449–54 hypercapnia 395 hypoxaemia 390 immunocompromised 1382–94 inflammation/coagulation interaction 1452 intra-abdominal 881 lung transplantation 1787 molecular diagnostics 1349–50 neutropenia 1304–5 nosocomial, see nosocomial infection pancreatitis 901 peritoneal dialysis 1024 post-cardiac surgery 1765 post-neurosurgery 1770 post-thoracic surgery 1766 index pregnancy 1757 prevention and control programme 1380 surveillance 1345–7, 1353, 1361–2 infection control ICU design pandemics 39 infective endocarditis, see endocarditis inflammasome 1451–2, 1463 inflammation acute kidney injury 1000–1 acute on chronic liver failure 941 ARDS 498–9 brain death 1867 calcium and 1203 coagulation and 1285–6, 1429, 1452, 1467–9 host response 1448–96 hypercapnia 395 hyperthermia 1687 inflammatory cascade 1427–30 innate immunity 1427–30 lower gastrointestinal haemorrhage 845 physiology 1426–30 pre-eclampsia 1749 repair and recovery 1476–80 respiratory muscle fatigue 353 septic shock 1416–17 traumatic brain injury 1628 infliximab 1386 influenza epidemics 1405–6 healthcare worker vaccination 1358 information exchange 29–30 information technology advanced informatics 5–6 integration in ICU 28–31 mass-casualty events and disasters 34 informed consent 104–5, 108–111, 114 informed decision-making 1856 infra-Hissian conduction block 733 infranodal AV block 731 infra-radian rhythms 1184 infringement of rights 115 inhalational anaesthetics 202–5 inhalation injury 492–5, 1552, 1659–60 inhaled nitric oxide 172, 503, 796 in-hospital recovery 1808–25 in-hospital stroke 1114 in-hospital transfer 14–18 innate immunity 1427–30, 1450–2, 1473, 1493 inotropes 158–60, 797–8, 1550–1 INR 1268, 1284 inspiratory time 431 inspired gas 322 insulin 813, 986, 1227 insulin-like growth factor-1 216 insulin-like growth factor-binding protein 1819 insulinoma 1259 insulin therapy 218–21, 1231, 1237–8 high-dose euglycaemic 1550, 1551 integrase inhibitors 1392 Intensive Care Delirium Screening Checklist (ICDSC) 1077 intensive care unit admission and discharge criteria 86–8 cost structure 92 design 3–6, 1359–60 evacuation 17 integrated information technology 28–31 staffing models 7–10 teamwork 43–5 intercostal muscles 350 interfaces 409, 412–13 interferon-beta therapy 503 interferon-gamma 1428, 1494 inter-hospital transport 19–22 interleukin-1 1428, 1489 interleukin biomarkers 1439 INTERMACS severity classification 718, 718 intermittent haemodialysis 1018–21 intermittent mandatory ventilation 472 internal jugular vein catheters 604 international normalized ratio (INR) 1268, 1284 interposition grafts 1599 interpreters 1858 interstitial fluid compartment 304 intestinal fistulae 890–1 intestinal fluid 814 intestinal ischaemia 877–9 intestinal obstruction 856–8 intra-abdominal abscess 822, 875 intra-abdominal hypertension 866–71, 901, 1595 intra-abdominal infection 881 intra-abdominal sepsis 822, 880–3 intra-aortic balloon pump 713–14, 1764 intracellular fluid compartment 304 intracerebral haemorrhage 1107, 1113, 1116, 1121–3 intracerebral microdialysis 1058 intracranial haematoma, post-operative 1770–1 intracranial haemorrhage, post-operative 1769 intracranial hypertension 1106–9 hypercapnia 396 intracerebral haemorrhage 1123 post-neurosurgery 1771 subarachnoid haemorrhage 1106–7, 1131 traumatic brain injury 1627–8, 1638 intracranial pressure 1039–40 monitoring 1059–62 intralipid emulsion 1513 intramural haematoma 689 intrathecal infusion devices 1650 intrathoracic pressure 400–1 intravascular fluid compartment 304 intravenous immunoglobulin 1170, 1489, 1494 intrinsic PEEP 386, 441, 513–14 intubating laryngeal mask airway 371, 374–5 intubation, see tracheal intubation inverse ratio ventilation 431, 438, 443–4 iodine 953 excess 1251 iodine disinfectant 79 ipratropium 145 iron 952 metabolism 1301 therapy 1302 ischaemia–reperfusion injury 697, 698–9, 1471–5, 1686–7 ischaemic post-conditioning 1474 isoflurane 202, 203–4, 205 isolation 1361 isoniazid 237, 239 isoprenaline 734 isopropyl alcohol 78 poisoning 1556–7 isoproterenol 171–2 isosorbide dinitrate 154 isradipine 154 istaroxime 159 itching 912, 914 itraconazole 240 ivabradine 163 J Jarvik 2000® 719 jaundice 904–14 classification 906 definition 905 diagnosis 907–9 intrahepatic 906, 913 management 911–14 monitoring 911–12 pathophysiology 906–7 post-hepatic 906, 913 prehepatic 906, 912–13 prevention 911 JC virus-induced PML 1387 jejunostomy feeding 974 Jod–Basedow effect 1251 joint contractures 1830 jugular venous oxygen saturation 1057, 1628 justice burnout 83 distributive 115 K KDIGO criteria 988, 989, 1004 Keeler–Cretin procrastination paradox 96 keraunoparalysis 1671 ketamine 190, 191, 1499, 1709 ketanserin 155 ketoacidosis 1213–14, 1219 ketoconazole 240 ketone bodies 953 ketorolac 191 kidney injury molecule (KIM-1) 1443, 1444, 1445–6 kidneys internal structure 983 respiratory alkalosis 528 shock 701 transplantation 1778–9 see also renal system Klebsiella spp. 1366 L labetalol 154, 693, 768, 1751 lacosamide 200 lactate monitoring 644–8 septic shock 1423 tissue oxygenation/perfusion 639, 642 lactic acid 314, 315 lactic acidosis 1213, 1218–19 salbutamol-induced 509 lactulose 177 Lake Louise score 1674 Lambert–Eaton myasthenic syndrome 1163 lamivudine 1392 landing injuries 1612 landmines 1618 laparoscopy 887 large conductance calcium-activated potassium channels 698 large intestine 814 large vessel vasculitis 1322–3 laryngeal mask airway 264, 371, 374–5 laryngeal tube 265 larynx, rheumatoid arthritis 1327 laser Doppler flowmetry 643, 1057 laser therapy, upper airway obstruction 366 Lassa haemorrhagic fever 1401 latex allergy 1499 latex fruit syndrome 1499 1891 1892 index laxative drugs 177–8 leadership skills 64–8 lead poisoning 1618 lean body mass 951 leaning 277 learning from defects 72–3 Lee Revised Cardiac Index Score 1722 leflunomide 1387 left bundle branch block 733 left heart catheterization 664 left heart unloading 153, 155 left ventricular diastolic function 653 left ventricular dysfunction 611 left ventricular ejection fraction 653 left ventricular filling pressure 653–4 left ventricular systolic function 652–3 legal issues 117–19, 1860 Legionella infections 544–5, 546, 1359 Legionella pneumophila 544–5, 1366 lenalidomide 1385 leptin 1483 leptospirosis 1405 lethargy 1085 leukaemias 1790–1 leukapheresis 1279–80 leukocyte-reduced blood components 1272–3 leukotriene antagonists 512 levalbuterol 145 levetiracetam 199–200 Levitronix CentriMag® 716 levofloxacin 238 levosimendan 155, 157, 159, 798 Lichtenberg figures 1671, 1671 LiDCO™ 633, 650 lidocaine 166, 383 ligation 1598–9 lightning strikes 1671 light transmission aggregometry 1267 limb trauma 1605 limited Wegener’s granulomatosis 1320–1 linaclotide 178 Lindeque criteria 1608 linezolid 196, 235 γ-linolenic acid 975 liothyronine 215–16 lipase, serum 896 lipid mediators 1429, 1430 lipids 952, 953 liposomal amphotericin 237, 239 lipoxin 1479 listening 48 Listeria monocytogenes 1366 literature review 102 lithium therapy 1512 live agents 78 liver bile 816–17, 818 blood supply 815, 826 chemotherapy complications 1804 chronic disease 257–8 cirrhosis 249–50, 940 critical illness 826–9 drug handling 818 extracorporeal support 913, 934–8, 946 function tests 827–9, 922 physiology 815–18 radiation-induced injury 1805 transplantation 928, 946, 1778 trauma 1594 tricyclic antidepressants poisoning 1531 liver failure diuretics 257–8 drug-induced 916–17, 1518, 1520 prescribing in 932 see also acute liver failure; acute on chronic liver failure liver function tests 827–9, 922 living wills 1858, 1860 LMA ProSeal® 264 lobar torsion 1766 local anaesthetics 190, 190 local cerebral oxygenation 1057 locked-in syndrome 1087 Logistic Organ Dysfunction System (LODS) score 131, 131, 132 logistics 5 long-term acute care hospitals 1810, 1841–3 long-term potentiation 1705 loop diuretics 257 lopinavir 1392 lorazepam 186, 186, 198, 1103 lower gastrointestinal haemorrhage 843–50 low-flow devices 141 low-frequency fatigue 353 low molecular weight heparins 223–4, 224, 1293 low T3 syndrome 956 loxiglumide 177 lubiprostone 178 lumbar plexus 1047, 1047 lung acute injury, see acute lung injury blast injuries 1615–16 blood flow 323 compliance 321 cyclic stress 467–8 extravascular water 314, 649–51 radiation-induced injury 1805 recruitment manoeuvres 553–8 resistance 322 rheumatoid arthritis 1326–7 stress/strain approach 467 transplantation 1785–7 trauma 1589–90 ultrasound 665 ventilator-associated injury 395, 443, 445–6, 499, 556–7 volumes 321 zones I–IV 323 luteinizing hormone 957 lymphocytes 1265 lymphoma 1791, 1791 lysine analogues 229–30 lysine vasopressin 150–1 M McCord hypothesis 1472–3 macrolides 175–6, 239 macrophages 1265, 1266, 1478 magnesium 953, 954 magnesium disorders 1198–200 magnesium salts 177 magnesium sulphate 168, 512, 727, 1200, 1751 magnesium supplements 1200 magnetic resonance imaging (MRI) abdomen 823–4 brain anoxia 1065 cardiac MR 665, 738, 739 cerebral blood flow 1057 endocarditis 749 fat embolism 1609 pancreatitis 896, 899 post-cardiac arrest 300 spine 1065 stroke 1064 traumatic brain injury 1631, 1634 unconsciousness 1085 urinary tract 994–5 malaria 1396–8, 1464 malignant hyperthermia 1172–3, 1175, 1687 malignant middle cerebral artery infarction 1107–8, 1118 malignant pleural effusion 580–1 Malnutrition Universal Screening Tool (MUST) 966 management 64 manganese 953 mannitol 258, 1638, 1697 manual handling 79 manual hyperinflation 561, 562 manual rib-cage compression 561, 562 maprotiline 194 maraviroc 1392 Marburg haemorrhagic fever 1401 MARS 935, 936, 936, 937 Marshall classification 1627, 1628, 1632, 1633 Marshall Score 896, 897 Maslach Burnout Inventory 82 mass-casualty events 32, 33–6 mass conservation 340–1 massive transfusion 1274 mast cell tryptase 1501–2 matrix metalloproteinases 1429, 1439 maximal static mouth pressures 353 maximum recruitment strategy 555–6 MDMA 1534–9 mean platelet volume 1267 mean systemic filling pressure 613 measles vaccination 1358 measured energy expenditure 970, 971 mechanical clot retrieval 1118 mechanical valves 740 mechanical ventilation airway pressure release ventilation (BiPAP) 141, 444–5 ARDS 432, 501 assisted-pressure controlled 443 atelectasis 550 breath sequences 422 bronchodilators 144–6 cardiac failure 712 COPD 432, 518–19 cycling 387, 421–2 design and function of ventilators 419–28 driving-pressure 467–8 dynamic hyperinflation 386, 506–9, 513–14 failure to ventilate 460–3 gas trapping 507, 513 gross barotrauma 465 high-frequency oscillatory ventilation 450–3 humidification 551 indications 415–18 indirect calorimetry 970 intermittent mandatory ventilation 472 long-term weaning centres 1841–3 lung recruitment manoeuvres 553–8 machine versus patient triggering 421–2 mandatory versus spontaneous breaths 422 mode of ventilation 422–7 neutrally-adjusted ventilatory assist mode 461–2 oxygen therapy 141 patient–ventilator interaction 386–7, 461–3 index positive end-expiratory pressure 433–6 pressure-controlled 421, 440–5 pressure support 447–9, 472 prone positioning 455–8, 554 pulmonary function 385–8 pulmonary hypertension 796 respiratory alkalosis 528 sedation 1813 setting rate, volume and time 430–2 sleep disturbances 1070 spinal cord injury 1645, 1648 spontaneous breathing trial 448 targeting schemes 422, 423 time control 421 toilet bronchoscopy 567–8 triggering 386, 421–2, 438, 447, 461–2, 463 variable 558 ventilator-associated lung injury 395, 443, 445–6, 499, 556–7 ventilator-associated pneumonia 531–3, 1346, 1370, 1375–6, 1638, 1731 ventilator-induced diaphragmatic dysfunction 353 ventilator trauma 465–8 ventilatory patterns 422 volume-controlled 421, 437–9 volutrauma 466–7 weaning 470–3, 972 weaning failure 474–6 withdrawal 448, 1862 mediastinum masses 364 trauma 1590–1 medical futility 302 Medical Research Council sumscore 1155, 1156, 1178, 1850 medico-legal liability 117–19 medium vessel vasculitis 1322 MEGX-Test 827, 922 MELD Score 827, 829 melphalan 1803 Mendelson’s syndrome 487–8 meninges 1039 meningitis 1137–47 antimicrobials 1143–5 clinical features 1140 CSF 1141 diagnosis 1140–1 epidemiology 1138–9 management 1143–6 pathophysiology 1139 tropical diseases 1405 meperidine (pethidine) 1499, 1708 meropenem 236, 238 mesenchymal stem cells 503, 1479 mesenteric ischaemia 875, 877, 1774 metabolic acidosis 328, 329, 1211–19 management 1215–19 pathophysiology and causes 1211–14 metabolic alkalosis 328, 329, 1220–3 metabolic system acute liver failure 919 acute on chronic liver failure 946 brain death 1867 burns 1654, 1660 coma 1088, 1090 hypokalaemia 1196 markers of tissue perfusion 641–3 peritoneal dialysis 1024 pregnancy 1746 response to critical illness 956–9 shock 701 subarachnoid haemorrhage 1135 metabolomics 133, 136 metacognition 57 13C-methacetin breath test 829 methadone 191, 1708–9 methamphetamine poisoning 1534–9 methanol poisoning 1557–8 methicillin-resistant Staphylococcus aureus 1347, 1357, 1367 methotrexate 1387, 1800–1, 1802, 1803, 1804 methylcellulose 177 methylene blue 151 methylhistamine 1502 methylnaltrexone 176, 178 methylphenidate 195, 195 methylxanthines 144 metoclopramide 175, 176, 854, 855 metolazone 256 metronidazole 237, 239 mexiletine 166 miconazole 240 microangiopathies 1277, 1296–7 microbial-associated molecular patterns 1462–3 microcirculation monitoring 643, 659–60 septic shock 1417 microRNAs 1435, 1441–2 microscopic polyangiitis 1321–2 microtubule inhibitors 1801, 1803, 1804 microvascular permeability 772, 773 midazolam 186, 186, 199, 1103, 1499 middle cerebral artery infarction 1107–8, 1118 Middle East respiratory syndrome coronavirus (MERS-CoV) 1406 migrating motility complex 813, 959 milnacipran 194 milrinone 155, 159, 170, 171, 798 minerals, nutritional requirements 952–3, 954 minimally cognitive state 1085 minimum alveolar concentration 203 Minnesota Sedation Assessment Tool 1713 minute ventilation 430, 508–9 mirtazapine 194, 195 misrepresentation 114–15 mitigating speech 44 mitochondrial permeability transition pore 1473 mitomycin-C 1802, 1803 mitral regurgitation 739, 742 mitral stenosis 738–9, 742 mitral valve replacement/repair 742 mivacurium 1499 mixed venous oxygen saturation 314, 315, 348, 623–6, 637–8, 1423 MMR vaccination 1358 Mobitz type block 732, 732 Mobitz type block 732–3 Model for Endstage Liver Disease (MELD) Score 827, 829 Modification of Diet in Renal Disease (MDRD) equation 1029–30 MODS 122–3, 130, 131, 131–2 molecular diagnostics 1349–50 molecular expression patterns 133–6 molybdenum 953 monitoring blood pressure 608–12 brain tissue oxygen 1057, 1062, 1628 cardiac failure 710 cardiovascular system 598–667 central venous pressure 613–17 cerebral blood flow and perfusion 1056–8 coagulation 1267–9 delayed cerebral ischaemia 1133–4 ECG 599–600 echocardiography 665 EEG 1050–5, 1091 enteral feeding 974 gastrointestinal system 819–29 haematological system 1262–70 in-hospital transfer 15, 16 intra-abdominal pressure 869 intracranial pressure 1059–62 ischaemic stroke 1118–19 jaundice 911–12 lactate 644–8 microcirculation 643, 659–60 mixed and central venous oxygenation 623–6, 637–8 neurological system 1049–66 neuromuscular blockade 208 non-invasive ventilation 413 organ donors 1867 oxygen therapy 141 oxygen transport 636–9 post-neurosurgery 1768 post-operative haemodynamic 1735 remote 30–1 renal function 988–91 respiratory system 325–61 right ventricular function 628–30 sedation 1054, 1712 tissue perfusion 640–3 toilet bronchoscopy 566 traumatic brain injury 1091 unconsciousness 1091 ventilation during CPR 270 monoamine oxidase inhibitors (MAOIs) 195, 195–6 monoclonal antibodies 1801 monocytes 1265, 1266 monomorphic ventricular tachycardia 724, 728 Monro–Kellie doctrine 1059 mood disorders 1836–8 morale 81 morphine 190, 1499, 1708 Mortality Prediction Model (MPM) 121, 122, 123, 126–7 motilin 812, 959 Motor Activity Assessment Scale 1713, 1714 motor cortex 1040, 1041 motor neuron disease 1155 mouth-to-mouth ventilation 269 MPM 121, 122, 123, 126–7 MR angiography, urinary tract 995 MRSA 1347, 1357, 1367 mTOR inhibitors 1384–5 mucosa, anaphylaxis 1500 mucus clearance 548–9, 560–3 multifocal atrial tachycardia 723, 727 multi-organ failure acute on chronic liver failure 941 jaundice 912 multiple-casualty incidents 32–3 multiple myeloma 1791 Multiple Organ Dysfunction Score (MODS) 122–3, 130, 131, 131–2 multiple organ dysfunction syndrome 774, 1428, 1456 multiple trauma 1580–613 1893 1894 index multivisceral transplantation 1779–80 mumps vaccination 1358 murmurs aortic regurgitation 738 aortic stenosis 737–8 mitral regurgitation 739 muromonab-CD3 1779 muscle relaxants 206–9; see also neuromuscular blockade muscles complications of critical illness 1828 contraction 1042 disuse atrophy 209 functional tests 965–6, 1155, 1156, 1178, 1850 hypokalaemia 1196 hypothyroidism 1253 ICU-acquired weakness 1176–9, 1812, 1828, 1849 respiratory 350–3, 404 muscle specific protein kinase 1161 muscular dystrophies 1157 musculoskeletal system chest pain 672 cocaine poisoning 1546, 1547 electrocution 1670–1 hypothyroidism 1253 MUSK antibodies 1161 myasthenia gravis 1156–7, 1160–2 myasthenic crisis 1162–3 myasthenic syndromes 1155, 1156–7, 1160–3 mycobacterial infection 585 mycophenolate mofetil 1385, 1779 Mycoplasma pneumoniae 545, 546, 1146, 1366 myelin 1042 myelin basic protein 1433, 1435 myeloid differentiation factor-88 1462, 1463 myeloid-related protein (Mrp8/14) 1452 myeloma with renal failure 1279 myeloperoxidase 1439 myocardial infarction criteria 678, 679 ST-elevation (STEMI) 682–7 myocardial perfusion scintigraphy 665 myocarditis 683 myocardium electrocution 1670 hypercapnia 396 shock 698–9, 1418 stunning 295 myopathies 1155, 1157–8 myotome 1047 myotonic dystrophy type I 1157–8 myxoedema coma/crisis 217, 1253–4 N N-acetylcysteine 1519 NADPH oxidase 1429, 1471–2 nafcillin 238 nalmefene 1524 naloxegol 176, 178 naloxone 176, 178, 1524 naltrexone 1524 napalm 1618 narrow complex tachycardia 726 nasal tube feeding 973 nasoduodenal feeding 973 nasogastric aspirates 854–5 nasogastric feeding 973 nasopharyngeal airway 264 natalizumab 1386, 1387 national health information exchange 29–30 National Institutes of Health Stroke Scale (NIHSS) 1117 natural killer cells 1265 nausea and vomiting 852–4, 1195–6, 1804–5 near infrared spectroscopy 1057–8 nebulizers 144–5 necrosectomy 901 necrotizing myopathy 509 needle aspiration 576–7 needle cricothyroidotomy 266 negative pressure wound therapy 871, 889–90, 1336, 1337, 1341 Neisseria meningitidis 1366, 1464 neocytolysis 1265 neonatal myasthenia gravis 1162 neostigmine 176, 177, 857 nerve conduction studies 1169 nervous system, see neurological system nervous system drugs 184–213 nesiritide 172, 257 neuralgia 672 neurocognitive impairment 1832–5 neuroendocrine system, see neurohormones neurogenic shock 703, 1647 neurohormones acute kidney injury 1001 immune response 1481–4 neurokinin A 1429 neurokinin antagonists 854 neuroleptic malignant syndrome 1173–4, 1175, 1687–8 neurological level of injury 1647 neurological system abdominal organ transplantation 1778 anaphylaxis 1500 anatomy and physiology 1038–48 chemotherapy complications 1804, 1804 drowning 1666 electrocution 1671 gastrointestinal system and 814 high altitude 1676 HIV 1393 hypothyroidism 1253 monitoring 1049–66 septic shock 1418 tropical diseases 1405 neuromediators 1429, 1430 neuromuscular blockade anaphylaxis 1499 ARDS 502 monitoring 208 muscle relaxants 206–9 post-operative 1731 reversal 209 traumatic brain injury 1637 neuromuscular electrical stimulation 1815 neuromuscular syndromes 1153–80 neuromuscular system complications of critical illness 1828 thyroid storm 1252 neuromuscular transmission 1042 neuronal injury hypoglycaemia 1227 markers 1434 neuron-specific enolase 299, 301, 1433, 1434 neuropathy 1155 neuroprotection 210–12, 1093–6, 1134, 1145 neurosurgery 1768–71 neutrally-adjusted ventilatory assist mode 461–2 neutropenia 1304–7 chemotherapy-related 1800 neutrophil gelatinase-associated lipocalin (NGAL) 1443, 1444, 1445–6, 1819 neutrophils 1265, 1461 apoptosis 1478 nevirapine 1392 new oral anticoagulants 226–7 New Orleans Criteria 1631–2 nicardipine 154, 768, 769 nicorandil 163 NICO system 634–5 nifedipine 154, 172, 769, 1752 nimodipine 154, 211, 212, 1134 nitrates 154, 156, 162 nitric oxide 697, 764, 1429 inhaled 172, 503, 796 nitric oxide inhibitors 151 nitric oxide synthase 1472, 1749 nitrogen balance 954 nitroglycerin 154, 156, 162 nitroprusside 154, 156, 172, 693, 768, 768 nitrosureas 1803 nitrous oxide 202, 204 Nocardia spp. 1366 nociception 1703–4 NOD-like receptors 1451–2, 1463 noise exposure 80 non-abandonment 114 non-beating heart organ donors 1870–2 non-depolarizing relaxants 207–8 non-dihydropyridine calcium channel blockers 162, 167 non-discrimination 114 non-Hodgkin’s lymphoma 1791, 1791 non-invasive ventilation 373, 411–13 ARDS 392, 412 asthma 392, 412, 514 bronchodilators 147 contraindication 393 COPD 392, 411, 518–19 hypoxaemia 391–2 monitoring 413 neuromuscular syndromes 1158 pneumonia 412 pulmonary oedema 391–2, 411 toilet bronchoscopy 568–9 non-nucleoside reverse transcriptase inhibitors 1392 non-occlusive mesenteric ischaemia 877, 879 non-opioid analgesics 191–2 non-STEMI coronary syndromes 678–80 non-steroidal anti-inflammatory drugs (NSAIDs) 190, 191 gastrointestinal haemorrhage 831 immunomodulation 1490–1 pain management 1709 non-thyroidal illness syndrome 215, 956, 957 norepinephrine (noradrenaline) 149–50, 159, 798 normal saline 308–9, 309 norovirus 861, 1360 Norton scale 1332 nortriptyline 194, 195, 1531 nosocomial infection 1351–81 antimicrobial selection 1363–8 definition 1352 device-related 1374–6 environmental decontamination 1359–62 epidemiology 1353 healthcare worker screening 1356–7 index indicators 1354 isolation 1361 pneumonia 531, 532, 533, 539–42 selective decontamination of the digestive tract 1369–72 standard precautions 1354–5 surveillance 1353, 1361–2 Novalung™ 482 nucleoside reverse transcriptase inhibitors 1392 NURSE mnemonic 48, 49 nurses 1863 Nursing Instrument for the Communication of Sedation 1713, 1714 NUTRIC score 966 nutrition 949–79 abdominal organ transplantation 1777–8 acute on chronic liver failure 946 ARDS 502 assessment of nutritional status 951, 964–7 colloids 249 corrosive poisoning 1566 digestion and absorption 811–12 enteral 181–2, 901, 973–6 essential nutrients 951–4 ileus/obstruction 858 immunonutrition 974–5, 978 intestinal fistulae 891 nutritional failure in critical illness 961–2 open abdomen 890 pancreatitis 901 parenteral 886, 901, 977–9 physiology 951–4 pressure ulcers 1332 response to critical illness 956–9 traumatic brain injury 1638 Nutritional Risk Index 966 Nutritional Risk Screening tool (NRS-2002) 966 nutritional status 951, 964–7 NXY-059 1474 O obesity 364 obesity-hypoventilation syndrome 412, 1069 Observer’s Assessment of Alertness and Sedation 1713, 1714 obstetric intensive care 1744–60 amniotic fluid embolism 1757–9 critical illness 1754–9 disseminated intravascular coagulation 1289 eclampsia 1747, 1751 haemorrhage 1754, 1756 HELLP 917, 1269, 1277, 1751 infection 1757 ovarian hyperstimulation syndrome 1759 physiological changes in pregnancy 1745–8, 1755 placental abruption 1289 pre-eclampsia 917, 1747, 1749–52 pulmonary embolism 1747, 1756–7, 1758 obstructive atelectasis 548 obstructive shock 696, 697, 702 obstructive sleep apnoea 363–4, 1068–9 obtundation 1085 occupational injuries 79–80 octreotide 177, 840, 1257 oedema, resistant 258 oesophageal pacing 734 oesophageal-tracheal double lumen airways 373–4 oesophagitis 831 oesophagogastroduodenoscopy 835, 839 oesophagus lower contractility 1713 peristalsis 813 rupture 671–2 trauma 1591 varices 831 oestradiol 957 oestrogens 216 offices 5 ofloxacin 236, 238 OKT3 1779 oliguria 988 diagnosis 1003–7 management 1008–11 pathophysiology 1002 omega-3 fatty acids 975 on-call suites oncological intensive care 1789–806 bone marrow transplantation 1795–9 chemotherapy complications 1800–5 haematological malignancy 1790–3 pain 1800 radiotherapy complications 1805 thromboembolic disease 1805 ondansetron 853 one-way endobronchial valves 578 open abdomen 871, 889–90, 1595–6 opioid-receptor antagonists 178 opioids acute withdrawal syndrome 1522 anaphylaxis 1499 dyspnoea 383 pain management 190, 190–1, 1708, 1709 poisoning 1522–5 spinal 1709 oral anti-hyperglycaemics 219 oral tolerance 812 orbidoxime 1571 organ donors 296, 1781, 1782, 1785, 1786, 1865–72 organ-failure scoring systems 122–3, 127, 130–2 oropharyngeal airway 264 oro-pharynx 813 orthogonal polarized spectral imaging 643, 659–60 orthostatic hypotension 1530 oseltamivir 237, 240 osmolol gap 1557 osmotic agents 257 outbreaks of resistance 1379 outcomes ICU admission and discharge criteria 88 neutropenia 1305 non-invasive ventilation 413 out-of-hospital support 1840–51 ovarian hyperstimulation syndrome 1759 overfeeding 962, 972 oxacillin 238 oxaliplatin 1804 oxidative stress 1227 oxygenation assessment 326–7 oxygen diffusion 323 oxygen extraction ratio 636 oxygen therapy 139–43 asthma 511 carbon monoxide poisoning 1561–3 cardiopulmonary resuscitation 264, 269 COPD 516 cyanide poisoning 1553 decompression illness 1679, 1680–1 defibrillation 270, 281–2 dose 140 dyspnoea 383 hyperbaric oxygen 141, 1561–3, 1679, 1680–1 hypoxaemia 391 indications 139–40 monitoring 141 neuroprotection 1095 pandemics 40 for poisoning 1511 post-cardiac arrest 294 pulmonary hypertension 796 routes of administration 141 safety issues 143, 270, 281–2 side-effects 141–2 oxygen transport 636–9 oxyhaemoglobin dissociation curve 327, 327 P pacing bradycardias 734 cardiac arrest 283 post-cardiac surgery 1764 paclitaxel 1801, 1803, 1804 PaCO2 327 pain 1702–10 analgesics 189–92, 1707–10 assessment 189, 1705 cancer-related 1800 Guillain–Barré syndrome 1170 management 1707–10 mechanisms 189 pathophysiology 1703–5 patient-controlled analgesia 1710 patients’ rights to effective management 114 peripheral nerve blocks 1709 post-neurosurgery 1770 palonosetron 853 Panc score 898 pancreas collections 895 hormone secretion 813 necrosis 895 pseudocysts 895 secretions 814 transplantation 1779 trauma 1594 pancreatic polypeptide 813 pancreatitis 893–903 abdominal compartment syndrome 901 diagnosis 896 gallstones 902 imaging 822, 896, 898–899 pathophysiology 894–6 severity assessment 896–9 splenic vein thrombosis 902 supportive care 900–1 pancuronium 207, 207 pancytopenia, chemotherapy-related 1800–1 pandemics 37–41 PaO2 326, 327 PaO2/FIO2 ratio 346–7, 390 papillary muscle rupture 686 paracellular permeability 773 paracetamol (acetaminophen) 190, 1709 poisoning 916–17, 1518–20 paraplegia 1647 1895 1896 index parapneumonic effusion 574, 579–80 parasympathetic neuromodulation 1483 parathyroid hormone 986 parentalism 1856 parenteral nutrition 886, 901, 977–9 Parkland formula 1658 paroxetine 193, 194 PARP hypothesis 1473 passive leg raise 314, 315 patent foramen ovale 1115–16 pathogen-associated molecular patterns (PAMPs) 1427, 1450, 1473 patient-controlled analgesia 1710 patient flow 34–5 patient rights 113–16 patient room 4, 1360 patient safety in ICU 71–3 pattern recognition receptors 1427, 1450–2, 1462–3 PD-1 1487 PEACE acronym 1079 PEEP 433–6 intrinsic 386, 441, 513–14 trial 434 PEEP valves 409 pelvic fracture 1582, 1584, 1601–5 pendelluft phenomenon 385, 452 penetrating aortic ulcer 689 penicillin G 235, 238 penicillins 238, 1499 pentobarbital (pentobarbitone) 199, 1103 pentostatin 1386 peptic ulcer disease 835–6, 875 peptide YY 813, 959 percent alpha trend 1054 perception/practice gap 75 percutaneous balloon mitral valvuloplasty 742 percutaneous cholecystectomy 887 percutaneous coronary intervention (PCI) intra-aortic balloon pump 713–14 non-STEMI coronary syndromes 680 post-cardiac arrest 287 STEMI 683–5 percutaneous dilatory tracheostomy 378 percutaneous pancreatic fluid aspiration 901 per diem method 92 performance measurement 75 pericardial effusion clinical finding 781 drainage 785–6 echocardiography 781–2 epidemiology and aetiology 780, 785 pericardial sclerosis 785 pericardial tamponade, see cardiac tamponade pericardiectomy 786 pericardiocentesis 785 pericardio-peritoneal shunt 786 pericarditis 1327 pericardium, echocardiography 655–6 peri-operative optimization 1725–8 peripheral arterial disease 1772, 1773 peripheral fatigue 353 peripherally-inserted central venous catheters 604 peripheral nerve blocks 1709 peripheral nervous system 1041–2, 1045–8 peripheral neuropathy, chemotherapy-induced 1804 peripheral perfusion 659 peripheral venous cannulae 602 peristalsis 813 peritoneal catheter 1023 peritoneal cavity 880 peritoneal dialysis 1022–4, 1034 peritonitis primary, secondary and tertiary 881 visceral perforation 875 permanent pacemakers 734 permissive hypercapnia 393, 395 peroxynitrite 697–8 personal conscience 115 pertussis vaccination 1358 pesticide poisoning 1568–72 PET cardiovascular system 665, 667 cerebral blood flow 1057 PET-CT 667, 749–51 pethidine 1499, 1708 pexelizumab 1474 pH, arterial blood gas 327 phaeochromocytoma 764, 1157–9 pharmacodynamics 932 pharmacokinetics 932, 1707–8 pharmacy 4–5 phenelzine 195, 195 phenindione 224 phenobarbital 199 phenol-based disinfectants 79 phentolamine 154, 157 phenylephrine 150 phenyl-t-butylnitrone 1474 phenytoin 199, 211–12, 212 phosphate disorders 1206–9 phosphate supplementation 1208 phosphodiesterase inhibitors 155, 157, 159, 170–1, 796–7, 798 phospholipase A2 1429 phosphorus 953 physical appearance 1830 Physical Function ICU Test 1851 physical recovery 1812–15 physical therapy 1813–14 physiological dead space 321, 348–9 physiological shunt 347–8, 389 physiotherapy post-thoracic surgery 1766 secretion clearance 551, 560–2 PiCCO® 633, 649 piperacillin 238 piperacillin-tazobactam 235, 238 PIRO staging system 1410 pituitary apoplexy 1246 disorders 1246–9 hormones 1183–4, 1185 surgery 1247–9 placental abruption 1289 placental growth factor 1750 plain radiographs abdomen 820 ballistic injury 1623 spinal cord injury 1642 upper airway obstruction 365 see also chest radiographs plasma exchange 936, 1170, 1276, 1277, 1322 plasmalyte A/B 309 plasmapheresis 936, 1170, 1276, 1277, 1322 plasma proteins 966 plasma transfusion 1273–4, 1290 plasminogen activators 1467 Plasmodium falciparum 1464 platelet activating factor 1429 plateletpheresis 1279 platelets 1266, 1267 platelet transfusion 1273, 1290 platinum analogs 1387, 1803 1804, 1804 pleural cavity disorders 570–82 pleural effusion exudate 573, 573–4, 579 malignant 580–1 management 579–82 parapneumonic 574, 579–80 pathophysiology 573–4 rheumatoid arthritis 1325–6 transudate 573, 574, 579 pleural empyema 1590 pleural fluid dynamics 572 pleural pressure 597 pleuritic chest pain 672 pleuroperitoneal shunts 582 pneumatosis intestinalis 822 pneumonia 530–46 aspiration 489–90, 1119 atypical 543–6 community-acquired 392, 408, 534–7 diagnostic accuracy 1876 hospital-acquired 531, 532, 533, 539–42 inhalation injury 493 non-invasive ventilation 412 post-operative 1731 ventilator-associated 531–3, 1346, 1370, 1375–6, 1638, 1731 pneumothorax 671 airflow limitation 510 definition and classification 575 diagnosis 575–6 iatrogenic 573, 575 management 576–7 pathophysiology 572–3 spontaneous 573, 573, 575 tension 575 traumatic 573, 573, 575, 1589–90 pocket mask 269 point-of-care testing 5, 1268–9 poisoning 1503–77 acetaminophen (paracetamol) 916–17, 1518–20 agricultural chemicals 1568–72 alcohol 1556–9 amphetamines 1534–9 benzodiazepines 1526–8 beta-blockers 1549–51 calcium channel blockers 1549–51 carbon monoxide 494, 1553, 1560–3, 1659 clenbuterol 1553 cocaine 1545–7 corrosives 1564–6 cyanide 494–5, 1552–5, 1659 decontamination 1509–10 diethylene glycol 1558–9 digoxin (digitalis) 1540–4 ecstasy 1534–9 enhanced elimination 1510–12 ethyl alcohol 1556 ethylene glycol 1558 hydrogen sulphide 1553 hyperlactataemia 645 isopropyl alcohol 1556–7 kinetics 1509 lead 1618 MDMA 1534–9 methamphetamine 1534–9 methanol 1557–8 index opioids 1522–5 pesticides 1568–72 radiation 1573–6 salicylate 1515–17 sodium azide 1533 toxicology 1505–8 toxidromes 1506, 1506, 1569–70 tricyclic antidepressants 1530–2 policies 75–7, 97 poly (ADP-ribose) polymerase-1 1473 polyarteritis nodosa 1322 polycarbophil 177 polyclonal antibodies 1386 polyethylene glycol (PEG) 176, 177 polygeline 310, 311 polymorphic ventricular tachycardia 724–5, 728 polyps airway 364 colorectal 845 polyuria 1249 porto-pulmonary hypertension 1776–7 positive end-expiratory pressure (PEEP) 433–6 intrinsic 386, 441, 513–14 trial 434 positive-pressure ventilation 404–6, 411–13 positron emission tomography (PET) cardiovascular system 665, 667 cerebral blood flow 1057 POSSUM 1722 post-cardiac arrest syndrome 294, 314–15, 316 post-conditioning 1474 post-intensive care syndrome 1822 post-mortem examination 1874–7 post-myocardial infarction syndrome 686 post-operative intensive care 1729–43 enhanced recovery 1727, 1737–42 fluids and circulation 1733–5 ventilation 1730–2 see also surgical intensive care post-operative issues central venous oxygen saturation monitoring 624–5 continuous positive airway pressure 408 nausea and vomiting 853 pulmonary hypertension 790–1 residual curarization 1731 risk assessment 1723 post-pyloric feeding 855 post-transfusion purpura 1278, 1296 postural mucus drainage 561, 562 potassium 953 potassium channel syndrome 1195 potassium disorders 1193–6 potassium infusion 1196 potassium sparing diuretics 257 power 64 pralidoxime 1571 pravastatin 211 predictive modelling 30 pre-eclampsia 917–18, 1747, 1749–52 pregabalin 191 pregnancy acetaminophen poisoning 1520 amniotic fluid embolism 1757–9 cocaine poisoning 1546 critical illness 1754–9 eclampsia 1747, 1751 HELLP 917, 1269, 1277, 1751 hypertension 153, 765, 1750–2 infection 1757 liver failure 917–18 ovarian hyperstimulation syndrome 1759 physiological changes 1745–8, 1755 placental abruption 1289 pre-eclampsia 917–18, 1747, 1749–52 pulmonary embolism 1747, 1756–7, 1758 pulmonary hypertension 793 radiation and 79 preload 595–6, 613 preoperative risk assessment 1721–3 pre-renal azotaemia 999, 1006 presensitization 1499 pressure-controlled mechanical ventilation 421, 440–5 pressure–flow relationship 323 pressure reactivity index 1062 pressure support ventilation 447–9, 472 pressure time index 416 pressure triggering 386, 438 pressure ulcers 1330–3, 1649 pressure–volume curve 337–8 pressurized metered-dose inhalers 144–5 primary end-to-end anastamosis 1599 primary survey 1581–2 pro-arrhythmia 168 probiotics 862, 975 procainamide 165, 728 procalcitonin 1348–9 procedural competencies 21–2 procedural due process 116 professional community standard 109 prognostication acute liver failure 923 EEG 1053–4 electrocution 1672 intracranial pressure 1061 post-cardiac arrest 296, 299–301 stroke 1116 traumatic brain injury 1632–4, 1639 unconsciousness 1091 Prognostic Inflammatory Nutritional Index 966 Prognostic Nutritional Index 966 prolactin 957 prolonged QT interval 724–5, 728 Prometheus 935, 936, 936, 937 prone positioning 455–8, 554 propafenone 166 propofol anaphylaxis 1499 infusion syndrome 200 sedation 186, 186–7, 1717 seizures/status epilepticus 200, 1103 propranolol 693 prostacyclins 764, 796 inhaled 172–3 intravenous 171 PGI2 pathway 698 prostaglandin E1 154 prostaglandins 154, 1490–1, 1749 prosthetic valve dysfunction 740 protease-activated receptors 1452, 1467–8 protease inhibitors 1392 proteases 1429 protective ventilation 1730 protein C, activated 1290, 1467, 1469, 1490 protein energy wasting 954 proteins 952, 953–4, 962 proteomics 133, 135 Proteus mirabilis 1366 Proteus vulgaris 1366 prothrombin-complex concentrate 1123 prothrombin time 1267–8, 1269 protocols 75–7 mass-casualty events and disasters 35 sedation 187–8, 1717–18 proton pump inhibitors 181–2 protriptyline 1531 prucalopride 176 pruritus 912, 914 pseudo-aneurysms 895–6 pseudochylothorax 1326 pseudohyperkalaemia 1193 Pseudomonas aeruginosa 1346, 1366 drug-resistant 1367 pseudothrombocytopenia 1296 psychoeducation 1837–8 psychological effects 80, 1846 psychological intervention 1837–8 psychosocial issues 1645, 1649–50 psyllium 177 pulmonary angiography 589 pulmonary arterial hypertension 155, 791–3 pulmonary artery catheterization 618–21 cardiac output assessment 632–3 oxygen delivery monitoring 636 pulmonary artery rupture 586 right ventricular function monitoring 628 pulmonary artery pressure 619–20, 628 pulmonary artery wedge pressure 619, 620 pulmonary capillary wedge pressure 313, 315 pulmonary embolectomy 798–9 pulmonary embolism 670–1, 800–8, 1292 cardiovascular consequences 802–3 causes 801 classification 801 combat injuries 1612 diagnosis 805–6 mortality 803 post-operative 1731–2 pregnancy 1747, 1756–7, 1758 pulmonary hypertension 789–90 respiratory failure 803 risk factors 801, 802 risk stratification 801–2 treatment 156, 806–7 pulmonary endarterectomy 798–9 pulmonary function mechanical ventilation 385–8 post-critical illness 1829–30 post-operative 1732 upper airway obstruction 365 pulmonary hypertension 787–99 acute illness 789–91 biomarkers 795 causes and epidemiology 789 chronic 791–3 classification 790 definitions 788 diagnosis 794–5 exacerbation 793 hypercapnia 395 management 155, 795–9 post-operative 790–1 pregnancy 793 sickle cell disease 1309–10, 1311–12 pulmonary oedema acute non-cardiogenic 776–8 cardiac failure 705–6, 709, 711 continuous positive airway pressure 408 high altitude 1676 non-invasive ventilation 391–2, 411 1897 1898 index pulmonary perfusion 323 pulmonary system abdominal organ transplantation 1776–7 acute on chronic liver failure 942 cardiac transplantation 1783 chemotherapy complications 1801–3 chest pain 672 cocaine poisoning 1546 HIV 1392–3 lung transplantation 1786–7 pancreatitis 894 peritoneal dialysis 1024 septic shock 1417–18 subarachnoid haemorrhage 1135 pulmonary vascular resistance 597 pulmonary vasodilators 170–3, 796–7 pulseless disease 1323 pulse oximetry 331–2, 345, 511 pulse pressure monitors 633–4 pulse pressure variation 313–14, 628 pulsus alternans 611 pulsus paradoxus 597, 611, 781 pulsus parvus 610 pulsus parvus et tardus 737 pulsus tardus 610 pyrazinamide 237, 239 pyruvate dehydrogenase 645 Q Q fever endocarditis 748 QT interval monitoring 600 QT prolongation 724–5, 728 quality-adjusted life years 95 quality control 1361–2 quality improvement 76–7, 105–6 quality of life tools 1845, 1846 quinine (quinidine) 165, 1397 quorum sensing apparatus 1450 R rabies 1146, 1165–6, 1405 rad 1573 radial artery catheters 604 radiation hazards 79 radiation injury 1573–6 radiation proctitis 845 radionuclide scanning acute acalculous cholecystitis 886, 887 pulmonary embolism 805 upper gastrointestinal haemorrhage 836 radiotherapy complications 1805 raltegravir 1392 Ramsay Sedation Score 1713, 1714 randomization 105 ranolazine 163 Ranson Score 897, 898 rapamycin (sirolimus) 1385, 1779 rapid response systems 11–13 rate control 726–7 reactive nitrogen species 1471–2 reactive oxygen species 1471–2 re-admission to ICU 1824 real time location systems reasonable patient standard 109 reboxetine 194 recognition 83 recombinant activated factor VII 231, 1123 recombinant human activated protein C 1290 recombinant human soluble thrombomodulin 1290 recombinant tissue plasminogen activator 1117, 1118 recovery 1091, 1476–80, 1807–51 recruitment manoeuvres 553–8 recurrent laryngeal nerve damage 365 red blood cells 1264–5 anaemia 1300–1 exchange 1398 storage lesion 1273 transfusion 1273, 1301–2 redox state 643 redox stress 1471–2 reduced intensity conditioning 1795 reflection HME filter 202–3 reflexes 1041 refractory period extension hypothesis 280 refusal of treatment 114 regional analgesia 189–90 regional delivery systems 24–6 regional health information exchange 29–30 rehabilitation 1823, 1835, 1838, 1849–51 relative adrenal insufficiency 1243 rem 1573 remifentanil 191, 1708 remote damage control resuscitation 1612–13 renal acidosis 1214, 1219 renal angiography 995 renal failure acute liver failure 919, 928, 932 acute on chronic liver failure 932, 941–2, 944–5 cocaine poisoning 1546, 1547 drug handling 1027–30, 1034 effect on critical illness 1032–4 electrocution 1671 malaria 1396, 1398 pancreatitis 895 renal replacement therapy 1013–25 acute liver failure 928 anticoagulation 1016–17, 1018–19 choice of mode 1015 continuous haemofiltration 1014–17, 1019, 1020 extended daily dialysis 1019 haemodialysis 1018–21 hyperkalaemia 1194–5 indications 1014 intermittent haemodialysis 1018–21 metabolic alkalosis 1222 peritoneal dialysis 1022–4, 1034 poisoning 1511 post-AKI renal recovery 1820 principles 1014–15 pulmonary hypertension 796 slow low-efficiency dialysis (SLED) 1019, 1020 stopping 1014 renal reserve 1004 renal system abdominal organ transplantation 1777 biomarkers of injury 1443–6 chemotherapy complications 1803–4 hypercapnia 396 hypokalaemia 1196 monitoring 988–91 physiology 983–6 post-AKI recovery 1816–20 post-cardiac surgery 1765 pregnancy 1746 post-thoracic surgery 1766 septic shock 1417 spinal cord injury 1649 vascular surgery 1773 renal tubular acidosis 985 renal tubule 983, 984–5 injury markers 990–1 renin 986 renin–angiotensin system 764 repositioning 1332 reptilase time 1267–8 research ethics 104–6 informed consent 104–5, 111 pandemics 41 translating into practice 73 residual volume 321 resistance 322, 336 resistive pressure 336 resource allocation 39, 1855 resource management 90–3 respiratory acidosis 328, 329, 330, 522–6 respiratory alkalosis 328, 329, 330, 527–8 respiratory drugs 138–47 respiratory failure acute 380–402 acute on chronic liver failure 946 cardiovascular interactions 399–401 post-operative 408 pulmonary embolism 803 tetraplegia 1650 respiratory muscles 350–3, 404 respiratory quotient 951, 971 respiratory sinus arrhythmia 399 respiratory system acute liver failure 918–19, 926 anaphylaxis 1500 brain death 1866–7 compliance 337, 338–9 elastance 337, 338–9 electrocution 1670 equation of motion 335, 421, 460 flow 336 HIV 1392–3 hypercapnia 394 hypothermia 1691 imaging 321–2, 355–60 monitoring 325–61 neural control 1041 organ donors 1868 physiology 321–3 pleural cavity 571–2 post-cardiac surgery 1764 post-neurosurgery 1769–70 post-thoracic surgery 1766 pregnancy 1745 resistance 322, 336 rheumatoid arthritis 1325 shock 701 spinal cord injury 1643, 1645, 1648–9 vascular surgery 1773 resting energy expenditure 970 resting metabolic rate 954 resuscitation 261–317 burns 1658–9 circulatory management 272–302 Do Not Attempt Resuscitation 1858 fluid management 303–17 hypothermia 1692 lower gastrointestinal bleeding 847 multiple trauma 1583–4 index obstetrics 1747–8 organ donors 1867–8 respiratory management 262–71 septic shock 1421–2 resuscitative thoracotomy 1582, 1583, 1588 reteplase 227 retinal haemorrhages 1676 return of spontaneous circulation 286 reversed coarctation 1323 reward 83 rewarming methods 1691–2 rhabdomyolysis 258, 1011, 1195, 1546, 1547, 1695–8 rheumatic heart disease 737, 738 rheumatoid arthritis 1325–7 rheumatoid lung 1326 rhythm control 727 ribavirin 1402–3 rib fracture 1588–9 riboleukograms 134 Richmond Agitation-Sedation Scale (RASS) 1077, 1713, 1714 rifampicin (rifampin) 237, 239 RIFLE criteria 989, 1004 Rift Valley fever 1401 RIG-1 1463 right atrial pressure 613 right bundle branch block 733 right heart catheterization 664, 795 right heart unloading 155–6 rights 113–16 right ventricular ejection fraction 628 right ventricular failure 788–9, 795 right ventricular function 627–30, 654–5 Riker Sedation-Agitation Scale 1713, 1714 rilpivirine 1392 Ringer’s acetate 309 Ringer’s lactate 309 risk stratification 120–36 acute kidney injury 1004–5 preoperative 1721–3 pressure ulcers 1332 pulmonary embolism 801–2 sepsis 1410 see also scoring systems rituximab 1321–2, 1386, 1803 rivaroxaban 224, 226 Rockall score 834 rocuronium 207, 208, 1499, 1501 room design 4, 1360 rotational thromboelastometry 1268–9, 1288 rotavirus 861 ROTEM 1268–9, 1288 RP interval 723, 724 rubella vaccination 1358 ‘rule of nines’ 1655, 1655 Rumack–Matthew nomogram 1519 S S1P agonists 777 S100A8 1452 S100B 301, 1434 sacral plexus 1047, 1048 safety early mobilization 1814 elective tracheostomy 377–8 environmental 78–80 fluid resuscitation 314 oxygen therapy 143, 270, 281–2 patient safety in ICU 71–3 transport teams 22, 22 salbutamol asthma 511–12 lactic acidosis 509 ventilated patients 145 salicylate poisoning 1515–17 saline hypertonic 1191, 1638 normal 308–9, 309 rhabdomyolysis 1696–7 salivary secretions 814 Salmonella spp. 1366 SaO2 326, 327 SAPS 121, 122, 123, 126 saquinavir 1392 SARS 1405 ‘SBAR’ format 15 sclerosing agents 785 scoring systems admission and discharge decisions 87 organ failure 122–3, 127, 130–2 pancreatitis 896–8 preoperative 1722–3 role and limitations 121–4 severity of illness 121, 122, 123, 125–8 upper gastrointestinal haemorrhage 834–5 SCORTEN scale 1317, 1318 scuba diving 1678 secondary survey 1584–5 second-degree AV block 732–3 secretin 812–13 security 5 sedation 1711–18 assessment 1712–15 daily interruption 1717 delirium risk 1074–5, 1078, 1078 EEG monitoring 1054, 1712 management 1716–18 mechanical ventilation 1813 medications 185–8, 1716–17 meningitis 1146 no sedation strategy 1718 post-neurosurgery 1768, 1769, 1770 protocols 187–8, 1717–18 scales 1713–15 strategies 1717–18 target level 1712 therapeutic hypothermia 296 toilet bronchoscopy 568 traumatic brain injury 1637 Sedation Agitation Scale (SAS) 1077 seizures 1097–104 aetiology 1099, 1099 antiseizure agents 198–200, 1638 assessment and management 1101–4 classification 1102 discrete 1099, 1101–3 EEG 1053, 1054 intracerebral haemorrhage 1122 ischaemic stroke 1119 meningitis 1146 pathophysiology and causes 1098–100 post-cardiac arrest 296 post-neurosurgery 1771 status epilepticus 1100, 1102, 1103–4, 1771 subarachnoid haemorrhage 1131 selective decontamination of the digestive tract 1369–72 selective oropharyngeal decontamination 1369–72 selective serotonin reuptake inhibitors (SSRIs) 193, 194, 196 discontinuation syndrome 196 selegiline 195, 195 selenium 953, 954 self-inflating bag 269–70 self-triggering 386 sensitivity analysis 96 SEPET 936, 936 sepsis 1407–24 acute kidney injury 1011 acute liver failure 918, 927 adaptive immunity 1486 adrenal insufficiency 1243 antibiotics 1412 assessment 1408–10 atrial fibrillation 723 biomarkers 1410 capillary leak 774 cholestasis 826 chronic renal failure 1033 coagulopathy 1285–6 corticosteroids 241–2 critical illness polyneuropathy 1828 definition 1408 diagnostic criteria 1409 disseminated intravascular coagulation 1288 early aggressive therapy 1413 epidemiology 1408 fluid resuscitation 315–16, 316 imaging 1410 intestinal fistula 890–1 intra-abdominal 822, 880–3 malaria 1398 management 1412–15 PIRO staging system 1410 pregnancy 1746–7, 1757 risk stratification 1410 sickle cell disease 1309–10, 1311 source control 1412–13 supportive therapy 1413–14 Surviving Sepsis Campaign 182, 776, 1420, 1421, 1489 tetraplegia 1650 thrombocytopenia 1296 work-up 1408–10 septic shock central venous oxygen saturation monitoring 625, 1423 endocarditis 760 fever 1685 fluid resuscitation 315–16, 316, 1421–2 management 156, 1420–3 myocardial dysfunction 698, 1418 pathophysiology 696, 697, 698, 1416–19 Sequential Organ Failure Assessment (SOFA) score 122–3, 127, 130–1, 131, 132 SERCA 2A activators 160 serotonin antagonists 853 serotonin norepinephrine reuptake inhibitors (SNRIs) 193, 194, 195 serotonin syndrome 1174–5, 1175 Serratia marcescens 1366 sertraline 193, 194 serum albumin 966 serum amylase 896 serum creatinine 1028 serum lipase 896 servant leadership theory 64 severe acute respiratory syndrome (SARS) 1405 severity of illness scoring systems 121, 122, 123, 125–8 1899 1900 index sevoflurane 202, 203–4, 205 sex hormones 957 sexual dysfunction 1846 shallow water blackout 1666 shared decision-making 1856, 1861 sharps management 79 Shigella spp. 1366 shock anaphylactic 703 blood pressure monitoring 610 burns 1658–9 cardiogenic 686, 696, 697, 702, 706, 713, 714, 716–18 diagnosis and management 700–3 distributive 696, 702 haemorrhagic 1459 hypovolaemic 696–7, 702 malaria 1398 neurogenic 703, 1647 obstructive 696, 697, 702 pathophysiology 696–9 spinal 1647 see also septic shock shunt 343, 389 physiological 347–8, 389 temporary 1599 sick euthyroid syndrome 956, 1253 sickle cell disease 672, 1308–12 sidestream dark field imaging 643, 660 Sievert 1573 sigmoid diverticulitis 875 signage 5 sildenafil 170–1, 796–7 silver-impregnated dressings 1337 Simplified Acute Physiology Score (SAPS) 121, 122, 123, 126 simulation training 60–3 simvastatin 211 single-pass albumin dialysis 936, 936 single photon emission computed tomography (SPECT) 665, 1057 sinus arrest 731, 732 sinus bradycardia 731, 731 sinus exit block 731 sinusoidal obstructive syndrome 1797 sirolimus 1385, 1779 skills clinical skills in critical care 56–9 family meetings 48 skin disorders 1314–28 anaphylaxis 1500 burns, see burns electrocution 1670 hypothyroidism 1253 intestinal fistulae 891 radiation injury 1576 spinal cord injury 1649 skin prick tests 1502 sleep disturbances 1068–70, 1676 sleeping sickness 1405 slips 80 Slit2N-Robo4 777 slow low-efficiency dialysis (SLED) 1019, 1020 slow ventricular tachycardia 289 small intestine motility 813 perforation 875 transplantation 1779–80 small vessel vasculitis 1320–2 smart displays smoke inhalation 492–5, 1552, 1659 smoking 676 snake bites 1289 sniff pressure 353 sodium azide poisoning 1553 sodium bicarbonate hypercapnia 396 hyperkalaemia 1194 rhabdomyolysis 1696–7 sodium chloride-impregnated dressings 1337 sodium deficit calculation 1191 sodium disorders 1189–91, 1770 sodium fusidate 236 sodium nitrite 1555 sodium nitroprusside 154, 156, 172, 693, 768, 768 sodium polystyrene sulphate 1511 sodium thiosulphate 1555 sodium zirconium cyclosilicate 1195 SOFA score 122–3, 127, 130–1, 131, 132 solid organ injury 1593–4 AAST grading scale 1586, 1586 solitary rectal ulcer syndrome 845 solitary toxic nodule 1251 somatosensory cortex 1040 somatosensory-evoked potentials 299, 300 somatostatin 177, 813, 840, 1257 somatotrophic axis 956 somnolence 1085 sorbitol 177 sotalol 167 source control 874–5, 882–3, 1306, 1412–13 specific elastance 339 specific lung elastance 339 SPECT 665, 1057 α-spectrin 1433, 1434 sphingosine-1-phosphate 777 spinal artery 1045 spinal cord anatomy and physiology 1043–5 ischaemia/infarction 1774 pain perception 1704–5 spinal cord injury 1641–51 airway manoeuvres 263 ASIA grade 1643, 1644, 1647 assessment 1643 cervical spinal injury 1647–50 cervical spine immobilization 1643 complete 1647 diagnosis 1642 epidemiology 1642 imaging 1151, 1642 management 1643–6 non-traumatic 1149–52 tetraplegic patients 1647–50 unstable spine 1643 spinal muscular atrophy 1157–8 spinal nerves 1043 spinal shock 1647 spinal trauma airway manoeuvres 263 imaging 1065 spinal veins 1045 spine imaging 1065 rheumatoid arthritis 1327 spirituality 1858 spirometry incentive 561, 562 upper airway obstruction 365 spironolactone 257 splenic injury 1593–4 splenic vein thrombosis 902 spontaneous breathing trial 448 spontaneous pneumothorax 573, 573, 575 sputum retention 548–51 sputum samples 535 staffing communication 4 models 7–10 nosocomial infection 1361 pandemics 38–9 transport team 20 welfare issues 81–4 staff lounge standard base deficit 1216 standard base excess 327, 1216 standard bicarbonate 329 standardized mortality ratio 123 standard of care 105 standard precautions 1354–5 Staphylococcus aureus methicillin-resistant 1347, 1357, 1367 methicillin-sensitive 1366 vancomycin non-susceptible 760, 1367 Staphylococcus epidermidis 1366 Starling equation 252, 305 statins acute lung injury 502–3 immunomodulation 1491 neuroprotection 210–11 stroke prevention 1120 status asthmaticus 395 status epilepticus 1100, 1102, 1103–4, 1771 stavudine 1392 Steinert’s myotonia 1157–8 ST-elevation myocardial infarction (STEMI) 682–7 stem cell therapy 503, 1479, 1792 Stenotrophomonas maltophilia 1366 stent thrombosis 686 sterile dressing technique 1341 sternum fractures 1589 wound infection 1765 steroids, see corticosteroids Stevens–Johnson syndrome 1317 Stewart–Hamilton equation 632 Stewart method 329 stimulants 195, 195 stomach 813, 814 storage areas streptococci, antibiotic choice 1366 Streptococcus pneumoniae genomic diversity 1464 penicillin-resistant 1367 penicillin-sensitive 1366 streptokinase 227 streptomycin 237, 239 stress adrenocortical response 1242 hyperglycaemia 1226–7 work-related 80, 81 stress ulceration 180–3, 832 stridor 363 stroke 1111–24 definition 1112 diagnostic assessment and investigations 1115–16 epidemiology 1112–14 FAST assessment 1115 haemorrhagic 1113, 1116, 1121–3 index imaging 1063–4 in-hospital 1114 ischaemic 1112–13, 1116, 1117–20, 1293 ischaemic penumbra 1115, 1116 management 1117–20, 1121–3 patent foramen ovale 1115–16 prognostic indicators 1116 rates and risk factors 1113–14 secondary prevention 1119–20 stroke volume variation 313–14 strong ion difference 329, 1211–12 strong ion gap 1212, 1217 Structured Clinical Interview for DSM-IV 1837 ST segment ischaemia 599–600 stupor 1085 subarachnoid haemorrhage 1125–36 acute phase 1133–5 aetiology 1127 aneurysm rupture 1133 assessment 1127–30 clinical features 1127 complications 1132–3 delayed cerebral ischaemia 1133–5 diagnostic algorithm 1129 epidemiology 1113, 1126 hyperacute phase 1131–3 imaging 1064–5, 1127–30 intracranial hypertension 1106–7, 1131 management 1131–6 neuroprotection 210–11, 1095 rebleeding prevention 1131, 1133 vasospasm 1133, 1334–5 subcutaneous linea alba fasciotomy 870–1 subjective global assessment 966 subjective standard 109 substance P 1429 substance withdrawal 1078–9 substitutes for leadership theory 64 succinylcholine 207 suctioning 551, 562–3 sudden death 760 sugammadex 209, 1501 sulfanegen 1555 sunburn 1676 superior vena cava catheters 605 superoxide 697–8 superoxide dismutase 1472 supplies 4, 34 supportive services 4–5 support surfaces 1332 suprachiasmatic nucleus 1184–5 supraglottic airway devices 264–5 supraventricular tachyarrhythmias 723 surface contamination 1360 surfactant 503 surge capacity 34, 37–8 surgery enhanced recovery programmes 1727, 1737–42 high-risk patients 1720–8 peri-operative optimization 1725–8 post-operative intensive care 1729–43 surgical airway 376–9 surgical cricothyroidotomy 266 surgical intensive care 1762–88 abdominal organ transplantation 1776–80 cardiac transplantation 1781–4 cardiothoracic surgery 1763–6 lung transplantation 1785–7 neurosurgery 1768–71 vascular surgery 1772–4 see also post-operative intensive care surrogate decision-making 104, 110–11, 114, 1856–7, 1860 surveillance, infection 1345–7, 1353, 1361–2 Surviving Sepsis Campaign 182, 776, 1420, 1421, 1489 survivor clinics 1845–7 sustained inflation manoeuvres 554 suxamethonium 1499 swallowing 813 SynCardia® Temporary CardioWest® Total Artificial 719 synchronized repolarization hypothesis 280 syndrome of inappropriate antidiuretic hormone 1191, 1248–9 system-based studies 105–6 systemic inflammatory response syndrome (SIRS) 918, 927, 941, 1449, 1456, 1828 systolic pressure variation 314 T tachyarrhythmias 721–8 causes and diagnosis 722–5 therapy 726–8 tacrolimus 1385, 1779 tagged red blood cell scan 848 Takayasu’s arteritis 1323 Takotsubo cardiomyopathy 683 tamponade, see cardiac tamponade TandemHeart® 716 TAPSE 655 targeted temperature control 286, 295–6, 1093–5, 1474–5, 1638 targeting schemes 422, 423 T cells 1265 teamwork 43–5, 53, 1857 technetium 99m scan acute acalculous cholecystitis 886, 887 pulmonary embolism 805 upper gastrointestinal haemorrhage 836 technology design of ICU telemedicine 51–2 see also information technology TEG 1268–9, 1288 tegaserod 176 teicoplanin 235, 238 tele-ICU 9 telemedicine 6, 51–3 temocillin 238 temperature-related disorders 1682–93 temporal arteritis 1322–3 temporary abdominal closure 871 temporary intracardiac pacing 734 tenectaplase 227 tenofovir 1392 Tensilon® test 1161 tension pneumothorax 575 tension-time index 351–2 Terson’s syndrome 1127 tertiary survey 1596 testosterone 957 tetanus 209, 1164–5 immunization 1164, 1165 tetracyclines 239 tetraplegia 1647–50 tezosentan 172 thalidomide 1385, 1804 therapeutic hypothermia 286, 295–6, 1093–5, 1474–5, 1638 Therapeutic Intervention Scoring System (TISS) 92, 123, 127 therapeutic misconception 111 thermal diffusion flowmetry 1057 thermodilution technique burns 1659 cardiac output 620–1 extravascular lung water 649–50 thiazide diuretics 257 thinking 56–7 THINK mnemonic 1078, 1078 thiopental (thiopentone) 199, 1499 third-degree heart block 733, 733 thoracentesis 581–2 thoracic bioimpedence 635 thoracic bioreactance 635 thoracic duct trauma 1591 thoracic surgery 1765–6 thoracic trauma 1588–91 thoraco-abdominal aortic aneurysm 1773 thoracotomy haemothorax 581 resuscitative 1582, 1583, 1588 Thoratec® 718 Thoratec HeartMate® II 719 THREAT acronym 1613 thrombapheresis 1279 thrombectomy 1598 thrombin 1282 thrombin time 1267–8 thrombocytopenia 1295–7, 1398, 1800 thromboelastography 1268–9, 1288 thrombolysis agents 227 contraindications 227 ischaemic stroke 1117, 1118 pulmonary embolism 806–7, 807 pulmonary hypertension 798 STEMI 685 thrombomodulin 1290 thromboprophylaxis 1292–3 thrombosis, see venous thromboembolism thrombotic thrombocytopenic purpura 1277, 1296–7 thymectomy 1163 thyroid disorders 1251–4 thyroid goitre 364, 1251 thyroid hormones 215–16, 956–7, 1186, 1251 thyroid storm 217, 1252–3 thyrotoxic crisis 1252–3 tianeptine 194 tidal volume 387, 438–9, 442 tight junctions 773 time control 421 tinzaparin 224 tirilazad 1474 tissue acidosis 524 tissue factor 1429, 1452, 1466–7, 1490 tissue factor pathway inhibitor 1467 tissue inhibitor of metalloproteinase-2 1819–20 tissue oximetry 639 tissue oxygenation 639, 640 tissue perfusion monitoring 640–3 tocilizumab 1386 toilet bronchoscopy 565–9 Toll-like receptors 958, 1451, 1462–3 topical antimicrobials 1337 topiramate 200 torsades de pointes 724 total energy expenditure 954 total lung capacity 321 1901 1902 index total nitrogen appearance 954 total non-volatile weak acids 329 toxic epidermal necrolysis 1317–18 toxic megacolon 861 toxic multinodular goitre 1251 toxicology 1505–8 toxidromes 1506, 1506, 1569–70 toxins 78; see also poisoning TP10 1474 trace amino-associated receptors 1535 tracheal dilatation and stenting 366 tracheal gas insufflation 397 tracheal intubation cardiopulmonary resuscitation 266 causing upper airway obstruction 364–5 difficult intubation 373–5 extubation 408, 473 extubation failure 474, 475 hypoxaemia 392–3 indications 391 muscle relaxants 208 pesticide poisoning 1571 spinal cord injury 1645 standard intubation in ICU 369–71 suctioning 551, 562–3 tracheobronchial injury 1590 upper airway obstruction management 366 weaning decisions 473 tracheobronchial injury 1590 tracheobronchial suctioning 551, 562–3 tracheomalacia 365 tracheostomy elective 376–9 follow-up 1846 percutaneous 378 spinal cord injury 1645, 1648 upper airway obstruction 366 training air medical transport 20, 21 in-hospital transfer 14–15 leadership 67–8 pandemic preparedness 40 simulation-based 60–3 tramadol 1709 tranexamic acid 229–30 transcellular fluid compartment 304 transcellular permeability 773–4 transcriptomics 133, 134–5 transdiaphragmatic pressure 353 transfer in-hospital 14–18 traumatic brain injury 1636–7 transfusion-associated circulatory overload 1274 transfusion-associated graft-versus-host disease 1798 transfusion reactions 1274, 1309, 1311 transfusion-related acute lung injury 502, 1274 transfusion-related ARDS 502 transient ischaemic attack 1112 transjugular intrahepatic portosystemic shunt (TIPS) 840, 841 transoesophageal echocardiography, see echocardiography transparency 30, 102 transparent film dressings 1335, 1337 transplantation abdominal organ 1776–80 bone marrow 1795–9 cardiac 1781–4 liver 928, 946, 1778 lung 1785–7 organ donors 296, 1781, 1782, 1785, 1786, 1865–72 transport of patients 19–22 transpulmonary lithium indicator 650 transpulmonary thermodilution 649–50 transthoracic echocardiography, see echocardiography tranylcypromine 195, 195 trauma abdominal 1593–6 ballistic 1614–24 blast injuries 1612, 1615–16 brain, see traumatic brain injury bullet wounds 1612, 1617–18 burns, see burns coagulopathy induction 1269, 1286 combat settings 1611–13 damage control resuscitation 1595, 1598, 1603, 1612, 1623 diagnostic evaluation 1585–6 disseminated intravascular coagulation 1288–9 FAST scan 821, 1582, 1623 fat embolism syndrome 1607–10 fluid resuscitation 316, 316 head injury 1585, 1585; see also traumatic brain injury host response 1455–8 limb 1605 multiple 1580–613 obstetrics 1747–8 pelvis 1582, 1584, 1601–5 pneumothorax 573, 573, 575, 1589–90 primary survey 1581–2 remote damage control resuscitation 1612–13 secondary survey 1584–5 spine, see spinal cord injury systematic approach 1581–6 tertiary survey 1596 thoracic 1588–91 thromboprophylaxis 1293 vascular 1597–600 ventilator-associated 465–8 traumatic brain injury 1625–40 assessment 1630–4 biomarkers 1432–5, 1628 blast waves 1616 cerebral autoregulation 1628 cerebral oxygenation 1628 classification 1626 combat injuries 1612 decompressive craniectomy 1637 diffuse axonal injury 1626–7, 1634 focal injuries 1626 hormone therapy 216–17 imaging 1063, 1631–2, 1634 intracranial hypertension 1627–8, 1638 management 1635–9 monitoring 1091 neuroprotection 211–12 pathophysiology 1627 primary injury 1627, 1635 prognosis 1632–4, 1639 risk factors for poor outcome 1627 secondary injury 1627, 1635, 1637 specialist referral 1636 transfer 1636–7 treatment refusal 114 TREM-1 1349, 1452 trepostinil 171 triage 39–40 triazoles 240 tricyclic antidepressants 194, 195 poisoning 1530–2 triggering 386, 421–2, 438, 447, 461–2, 463 triggering receptor expressed on myeloid cells-1 1349, 1452 tri-iodothyronine 215–16 trimetaphan 155, 157 trimethoprim 239 trimethoprim/sulfamethoxazole 236, 239 trimipramine 1531 triple rule-out CT 692 tromethamine 396–7 tropical diseases 1395–406 troponins 679, 679, 1437–41 trypsinogen-2 896 tryptase 1501–2 T-tube trial 471–2 tuberculosis haemoptysis 584, 585 healthcare worker screening 1357 tube thoracostomy 577, 582, 1589–90 tubing volume 348 tumour lysis syndrome 1792, 1803–4 tumour necrosis factor-α 1428, 1439, 1489 tunnelled venous lines 1798–9 tyramine 195 tyrosine kinase inhibitors 1801 U ubiquitin C-terminal hydrolase-1 1434 ultradian rhythms 1184 ultrasound abdomen 820–1 acute acalculous cholecystitis 886, 887 cardiovascular system 664–5 central venous access guidance 606 FAST scan 821, 1582, 1623 hypoxaemia 390 pancreatitis 896 pleural effusion 579 pneumothorax 575–6 sepsis 1410 urinary tract 992–4 unconsciousness 1082–96 aetiologies 1084–5 clinical disorders 1085 diagnostic approach 1085–7 differential diagnosis 1087 management 1088–91 uncontrolled non-beating heart organ donors 1870 underfeeding 961–2, 971–2 unfractionated heparin 223, 224, 224, 1293 unit-based antibiograms 1365 upper airway obstruction 363–7 upper gastrointestinal tract endoscopy in corrosive poisoning 1565–6 haemorrhage 831–7 upper limit of vulnerability hypothesis 280 urea 989 urgent transfusion 1274 urinary alkalinization 1511 urinary tract catheter-associated infections 1376 imaging 992–6 urine volume 988 index V vaccination, healthcare workers 1357–8 vagus nerve 1430 valproate 200 VALUE mnemonic 48, 49, 1857 values 83 valvular disease 736–42 vancomycin 235, 238 vancomycin-resistant staphylococci 760, 1367 Vancouver Interaction and Calmness Scale 1713 Van Slyke equation 1216 vaporized H2O2 1361 variable mechanical ventilation 558 variable vessel vasculitis 1323–4 variceal bleeding 831, 832, 838–41 vascular access 602–6, 1033 vascular anomalies 1289 vascular endothelial cadherin proteins 773 vascular endothelial growth factor 777 vascular endothelium, see endothelium vascular flow 597 vascular hyporesponsiveness 697–8 vascular surgery 1772–4 vascular trauma 1597–600 vasculitis 1320–4 vasoactive intestinal peptide 1483 vasoactive substances 279, 764–5, 1422–3 vasodilators 153–7, 1009 vasopressin 150–1 acute variceal haemorrhage 840 capillary leak 777 immune response 1483–4 pulmonary hypertension 798 vasopressors 149–51 anaphylaxis 1501 beta-blocker and calcium channel blocker poisoning 1550 cardiopulmonary resuscitation 285–6 pulmonary hypertension 797–8 vasospasm 1133, 1134–5 prevention 210–11 Vaughan-Williams classification 166 VE-cadherin 773 vecuronium 207, 207 vegetative state 1085 velusetrag 176–7 venlafaxine 193, 194, 195 veno-occlusive disease 1797 venous cannulation 602–6 venous oximetry 623–6 venous return 613 venous thromboembolism 1292–4 acute on chronic liver failure 942 cancer patients 1805 Guillain–Barré syndrome 1170 high altitude 1676 intracerebral haemorrhage 1123 ischaemic stroke 1119, 1293 muscle relaxants 209 pelvic fracture 1604 post-neurosurgery 1770 pregnancy 1747, 1756–7 spinal cord injury 1645, 1649 trauma 1293 traumatic brain injury 1638 veno-venous extracorporeal life support 480–1 ventilation acid–base disturbances 327–30 assessment 327–30 asthma 513–14 cardiopulmonary resuscitation 268–70 continuous positive airway pressure 141, 407–9 as exercise 401 Guillain–Barré syndrome 1170 harm avoidance 1812–13 high-frequency oscillatory 450–3 in-hospital transfer 16 inverse ratio 431, 438, 443–4 lung volumes 321 mechanical, see mechanical ventilation minute 430, 508–9 muscle relaxants 208 neuroprotection 1095–6 non-invasive, see non-invasive ventilation pandemics 40 pesticide poisoning 1571 positive-pressure 404–6, 411–13 post-neurosurgery 1768, 1769 post-operative 1730–2 protective 1730 pulmonary circulation 791 spinal cord injury 1645, 1648 traumatic brain injury 1637–8 ventilation/perfusion matching 341–2 ventilation/perfusion mismatch 342–3, 389 ventilation/perfusion ratio 341 ventilation–perfusion scintigraphy 805 ventilator-associated lung injury 395, 443, 465–6, 499, 556–7 ventilator-associated pneumonia 531–3, 1346, 1370, 1375–6, 1638, 1731 ventilator-induced diaphragmatic dysfunction 353 ventilator trauma 465–8 Ventrassist® 719 ventricular assist devices 481–2, 716–20 ventricular dysfunction, post-cardiac surgery 1763, 1764 ventricular failure 706–7 ventricular fibrillation 289, 292 ventricular septal defect 686 ventricular tachycardia 289, 292, 724–5, 728 ventriculo-arterial coupling 707 ventriculostomy 1095 verapamil 162, 167 vesiculo-vacuolar organelles 773, 774 vessel repair 1598–9 Vibrio cholerae 1366 Vibrio vulnificus 1366 video-assisted thoracic pericardiectomy 786 video capsule endoscopy 836 videolaryngoscopy 371 vigabatrin 1536 vilazodone 194 vincristine 1386, 1804 viral haemorrhagic fevers 1400–3 viridans streptococci 1366 virtual device communities 5–6 virtual electrode polarization hypothesis 280 visceral perforation 872–6 visual cortex 1040 vital capacity 321 vitamin B12 deficiency 1301 vitamin D 216, 957, 986 vitamin K antagonists 224, 226 vitamins, nutritional requirements 952, 954 vocal cord dysfunction 365, 511 voltage-gated calcium channel antibodies 1163 volume-controlled mechanical ventilation 421, 437–9 volume kinetics 253 volume/outcomes relationship 24 VolumeView™ 633 vomiting 852–4, 1195–6, 1804–5 vorinconazole 237, 240 W waiting room 4 ‘walking the process’ 73 Warburg effect 645 warfarin 224, 226 warming methods 1691–2 waste management 4, 79 water balance 985 water deficit 1190 Waterhouse–Friedrichsen syndrome 1242 watermelon stomach 832 waveform capnography 266, 270 weaning 470–3, 972 failure 474–6 long-term centres 1841–3 wedged hepatic venous pressure 838 Wegener’s granulomatosis 1320–1 weighted procedure method 92 weight loss 965 Weir equation 969 Wenkebach block 731, 732, 732 white blood cells (count) 1265–6, 1348 white phosphorous 1618 WHO, surgical safety checklist 1722–3 whole bowel irrigation 1510 ‘wind up’ 1705 withdrawing and withholding treatment 1854–64 work community 83 workflow automation 29 workload 83 wound cleanser 1335 wound dressings 1334–41 wound infection post-cardiac surgery 1765 post-neurosurgery 1770 wrist actigraphy 1713 X xanthine oxidase 1472–3 Xenaderm™ 1337 xenon 202, 204, 205 X-ray, see chest radiographs; plain radiographs Y yellow fever 1401 Z zanamivir 237, 240 Zargar score 1566, 1566 zidovudine 1392 zinc 953, 954 Zollinger Ellison syndrome 832 zone of coagulation 1653–4 zone of hyperaemia 1654 zone of partial preservation 1647 zone of stasis 1654 1903 ... Copyright Elsevier 20 12 As an energy source, glucose is oxidized to CO2 and water: C 6H12O6 + 6O2 + 32ADP + 32P − > CO2 + 6H2O ( + 32ATP + heat RQ = 6CO2 / 6O2 = 1.0 ) [eqn 2] At rest, the maximum... Journal of the American College of Surgeons, 21 2, 703– 12 12 De Backer D, Biston P, Devriendt J, et al (20 10) Comparison of dopamine and norepinephrine in the treatment of shock New England Journal of. .. Metabolic Care, 15 (2) , 174–80 Jensen GL and Wheeler D (20 12) A new approach to defining and diagnosing malnutrition in adult critical illness Current Opinion in Critical Care, 18 (2) , 20 6–11 Jensen