Common choices for speci \201 c organisms S. aureus MRSA S. pneumoniae Cefuroxime, benzylpenicillin N. meningitidis Ceftriaxone, cefo taxime, benzylpenicillin Cefuroxime, cefotaxime H. in \202 uenzae Ampicillin, ceftazidime, cipro \202 oxacin, gentamicin, imipenem, E. coli meropenem Flucloxacillin Teicoplanin, vancomycin, linezolid Klebsiella spp. Ceftazidime, cipro \202 oxacin, gentamicin, imipenem, meropenem Ceftazidim e, cipro \202 oxacin, gentamicin, imipenem, meropenem, P. aeruginosa piptazobactam See also: Virology, serology and assays, p226; Infection \200\224treatment, p554; Multi-res istant infection, p562. 328 CHAPTER 20 Miscellaneous drugs Corticosteroids Uses \200 Anti-in \202 ammatory \200\224corticosteroids are often given in high dose for their anti- in \202 ammatory effect, e.g. asthma, allergic and anaphylactoid reactions, vasculitic dis orders, rheumatoid arthritis, in \202 ammatory bowel disease, neoplasm-related cerebral oe dema, ARDS, laryngeal oedema (e.g. after intubation), and after spinal cord injury. Bene \201 t is unproven in cerebral oedema following head injury or cardiac arrest. Infection \200\224though their immunosuppressive actions may increase susceptibility to infection, co rticosteroids are often used with antibiotics as \201 rst-line therapy to reduce the in \202 ammatory response of microbial killing, e.g. miliary TB, bacterial meningitis, pneumoc ystis pneumonia. Only in cerebral malaria has speci \201 c detriment been shown. In septic shock, high dose, short-course corticosteroids were ineffective/detrimental. However, more recent trials found improved survival with \200\230low dose \200\231 hydrocortisone (50mg qds) 9 \202 udrocortisone (50mcg), although only in the severe \200\230vasopressor-unre sponsive \200\231 subset. Pressor requirements fell faster with corticosteroid therapy. The short corticotropin (ACTH) test is not reliable in determining adrenal responders from non -responders. Free cortisol levels should ideally be assayed, but this is not routinely offe red by hospitals. Replacement therapy \200\224for patients with Addison \200\231s disease a nd post-adrenalectomy or pituitary surgery. Fludrocortisone is also usually required long-t erm for its mineralocorticoid Na+ retaining effect. Higher replacement doses are needed in chronic corticosteroid takers undergoing stress, e.g. surgery, infection. Immunosuppressive \200\224after organ transplantation. Side effects/complications \200 \200 \200 \200 \200 \200 \200 \200 Sodium and water retention (especially with mineralocorticoids). Hypoadrenal crisis if stop ped abruptly after prolonged treatment. Immunosuppressive: increased infection risk. Neutro philia. Impaired glucose tolerance/diabetes mellitus. Hypokalaemic alkalosis. Osteoporosis, proximal myopathy (long-term use). Increased susceptibility to peptic ulcer disease and GI bleeding. Notes \200 Oral fungal infection is relatively common with inhaled corticosteroids, but systemic and p ulmonary fungal infection is predominantly seen in the severely immunocompromised (e.g. AID S, post-chemotherapy) and not those taking high-dose corticosteroids alone. Choice of corti costeroid for short-term anti-in \202 ammatory effect is probably irrelevant, provided the dose is suf \201 cient. Chronic hydrocortisone should be avoided for anti-in \202 ammato ry use because of its mineralocorticoid effect, but is appropriate for adrenal replacement. Prednisone and cortisone are inactive until metabolized by the liver to prednisolone and h ydrocortisone, respectively. Glucocorticoids antagonize the effects of anticholinesterase d rugs. Corticosteroids probably do not cause critical illness myopathy. CORTICOSTEROIDS 329 Relative potency and activity Equivalent anti- in \202 ammatory dose (mg) 25 0.75 20 4 5 5 \200\223 Glucocorticoid activity ++ ++++ ++ +++ +++ +++ + Mineralocorticoid activity ++ \200\223 ++ + + + ++++ Drug Cortisone Dexamethasone Hydrocortisone Methylprednisolone Prednisolone Prednisone Flud rocortisone Drug dosages Anti-in \202 ammatory dose 4 \200\22320mg tds IV 100 \200\223200mg qds IV 500mg \200\2231g IV daily 40 \200\22360mg od PO \200\223 Drug Dexamethasone Hydrocortisone Methylprednisolone Prednisolone Fludrocortisone Replacement dose \200\223 20 \200\22330mg daily \200\223 2.5 \200\22315mg mane 0.05 \200 \2230.3mg daily Weaning Acute use (<3 \200\2234 days): Short-term use ( \211 3 \200\2234 days): Medium-term use (weeks): Long-term use (months/years): can stop immediately. wean over 2 \200\2235 days. wean over 1 \200\2232 weeks. wean slowly (months to years). Key papers Bracken MB, Shepard MJ, Holford RT, et al. (1997) Administration of methylpredni solone for 24 or 48 hours or tirilazad mesylate for 48 hours in the treatment of acute spin al cord injury. Results of the Third National Acute Spinal Cord Injury Randomized Controlle d Trial. National Acute Spinal Cord Injury Study. JAMA 277: 1597 \200\223604. Prasad K, Garner P. (2000) Steroids for treating cerebral malaria. Cochrane Database Syst R ev. (2): CD000972. Review. de Gans J, van de Beek D; European Dexamethasone in Adulthood Bacterial Meningitis Study In vestigators. (2002) Dexamethasone in adults with bacterial meningitis. N Engl J Med 347: 15 49 \200\22356. Annane D, S bille V, Charpentier C, et al. (2002) Effect of treatment with low doses of hy drocortisone and \202 udrocortisone on mortality in patients with septic shock. JAMA 288: 862 \200\22371. Sprung C, Annane D, Keh D, et al for the CORTICUS study group. (2008) Hydrocortisone therap y for patients with septic shock. N Engl J Med 358: 111 \200\22324. See also: Electrolytes (Na+, K+, Cl \200\223, HCO3 sepsis, p332; Airway obstruction, p348; Acute respiratory distress syndrome (2), p364; Asthma \200\224 general management, p364; Me ningitis, p446; Raised intracranial pressure, p454; Myasthenia gravis, p458; Platelet disor ders, p478; Hypercalcaemia, p494; Hypoadrenal crisis, p524; Sepsis and septic shock \200 \224treatment, p560; HIV related disease, p566; Rheumatic disorders, p572; Vasculitis, p574 ; Anaphylactoid reactions, p578; Spinal cord injury, p590. \200\223), p212; Full blood count, p220; Immunomodulatory therapies in 330 CHAPTER 20 Miscellaneous drugs Prostaglandins Types \200 \200 Epoprostenol (prostacyclin, PGI2). Alprostadil (PGE1). Modes of action \200 Stimulate adenyl cyclase, thus increasing platelet cAMP concentration; this inhibits phosph olipase and cycloxygenase, and thus reduces platelet aggregation (epoprostenol is the most potent inhibitor known). Reduces platelet procoagulant activity and release of heparin neut ralizing factor. May have a \201 brinolytic effect. Pulmonary and systemic vasodilator by relaxation of vascular smooth muscle. \200 Uses \200 Anticoagulation, particularly for extracorporeal circuits, either as a substitute or in add ition to heparin. Pulmonary hypertension. Microvascular hypoperfusion (including digital va sculitis). Haemolytic uraemic syndrome. Acute respiratory failure (by inhalation). \200 \200 \200 Side effect and complications \200 \200 \200 Hypotension. Bleeding (particularly at cannula sites). Flushing, headache. Notes \200 Epoprostenol is active on both pulmonary and systemic circulations. Although alprostadil is claimed to be metabolized in the lung and have only pulmonary vasodilating effects, falls in systemic blood pressure are not uncommonly seen, especially if metabolism is incomplete. Avoid extravasation into peripheral tissues as solution has high pH. Effects last up to 30 min following discontinuation of the drug. Prostaglandins may potentiate the effect of hepa rin. Recent studies have shown improvement in gas exchange by selective pulmonary vasodilat ation following inhalation of epoprostenol at doses of 10 \200\22315ng/kg/min. The ef \201 cacy appears similar to that of nitric oxide inhalation, but is not as rapid. \200 \200 \200 PROSTAGLANDINS 331 Drug dosages Epoprostenol Alprostadil 2 \200\22320ng/kg/min 2 \200\22320ng/kg/min See also: Haemo(dia)diltration (2), p110; Vasodilators, p266; Anticoagulants, p318; Vasculi itis, p574. 332 CHAPTER 20 Miscellaneous drugs Immunomodulatory therapies in sepsis Agents modulating different components of the in \202 ammatory response have been studied. These target triggers (e.g. endotoxin), cytokines (e. g. tumor necrosis factor, interleukin-1, and effector cells and their products (e.g. neutro phils, free oxygen radicals, NO)), aim to replace or boost often depleted endogenous anti-i n \202 ammatory response systems, e.g. corticosteroids, activated protein C, antithrombin, immunoglobulin. However, there is a variable degree of disruption and imbalance between pro- and anti-in \202 ammatory systems. Outside small research studies, current monitoring capability preclu des the ability to determine which patient would bene \201 t from either boosting or suppr essing their in \202 ammatory response, and to what degree, at a precise point of time. Th is issue has likely affected identi \201 cation of subgroups who could have bene \201 ted from a large number of immunomodulatory drug trials that have failed to show outcome bene \201 t. Only corticosteroids in severe septic shock, and activated protein C (also in a mo re severe subset) have dem- onstrated mortality reduction in reasonably sized multicentre t rials. For the others, promising results from post hoc subgroup analysis and from tightly c ontrolled small patient studies have not been reproduced. Activated protein C Drotrecogin alfa (activated) is a recombinant form of activated protein C and has anti-in \202 ammatory, anticoagulant and \201 brinolytic properties. Its ben- e \201 cial role in adult sepsis is most likely related to anti-in \202 ammatory effects . The pivotal PROWESS study demonstrated overall outcome bene \201 t for patients with sev ere sepsis treated within 48h of presentation with a 96h infusion of 24mcg/kg/h. However, s ubset analysis showed bene \201 t was restricted to those with a higher risk of death. Sub sequent studies have failed to show bene \201 t in lower risk adults (APACHE score <25) or in children. The major side effect is bleeding so caution should be exercised in those at high risk of potentially catastrophic bleeding, e.g. concurrent coagulopathy or a recent hi story of surgery, major trauma, head injury and/or peptic ulcer disease. Ongoing trials are attempting to reproduce the PROWESS \201 ndings and to use plasma protein C levels as a biomarker against which treatment will be titrated. Corticosteroids Hydrocortisone (50mg qds) 9 \202 udrocortisone (50mcg) improves survival in severe \200\230vasopressor-unresponsive \200\231 sepsis. Immunoglobulin (IV Ig) Intravenous immunoglobulin (IV Ig) has been studied in both general sepsis and in speci \201 c toxin-related conditions. Meta-analyzes suggest bene \201 t in general sepsis though no single large study has shown signi \201 cant survival bene \201 t. A single dose of 2g/kg should be given, and repeated only if the patient relapses after initial response. If an anaphylactoid reaction occurs, slow down/stop infusion and conside r corticosteroids. Uses \200 \200 Severe invasive group A streptococcal disease (e.g. necrotising fasciitis). Staphylococcal toxic shock syndrome or necrotising (Panton-Valentine Leukocidin (PVL)-associated) staphylo coccal sepsis. Severe or recurrent Clostridium dif \201 cile colitis. IMMUNOMODULATORY THERAPIES IN SEPSIS 333 Examples of drugs investigated in multi-center studies \200 \200 \200 \200 \200 \200 \200 \200 \200 \200 \200 \200 \200 \200 \200 Corticosteroids (methylprednisolone, hydrocortisone). Immunoglobulin. Anti-endotoxin antibo dy (HA-1A, E5). Anti-tumor necrosis factor antibody. Tumor necrosis factor soluble receptor antibody. Interleukin-1 receptor antagonist. Platelet activating factor antagonists, PAF-a se. Bradykinin antagonists. Naloxone. Ibuprofen. N-acetylcysteine, procysteine. L-N-mono-me thyl-arginine (L-NMMA). Antithrombin. Tissue factor pathway inhibitor. Activated protein C. Key papers Bernard GR, for the PROWESS study group. (2001) Ef \201 cacy and safety of reco mbinant human activated protein C for severe sepsis. N Engl J Med 344: 699 \200\223709. Annane D, S bille V, Charpentier C,et al. (2002) Effect of treatment with low doses of hyd rocorti- sone and \202 udrocortisone on mortality in patients with septic shock. JAMA 288 : 862 \200\22371. Sprung C, Annane D, Keh D, et al for the CORTICUS study group. (2008) Hydrocortisone therap y for patients with septic shock. N Engl J Med 358: 111 \200\22324. Turgeon AF, Hutton B, Fergusson DA, et al. (2007) Meta-analysis: intravenous immunoglobulin in critically ill adult patients with sepsis. Ann Intern Med 146: 193 \200\223203. See also: Corticosteroids, p328; Sepsis and septic shock \200\224treatment, p560. 334 CHAPTER 20 Miscellaneous drugs Rituximab This is an anti-CD20 antibody directed against B lymphocytes that is \201 nding increasing use in a variety of hematological, immune, and rheuma- tological conditions. Ma ny of its uses are still off-label, but it is increasingly popular. Modes of action \200 Anti-CD20 antibody directed against normal and malignant B cells. Uses \200 \200 Non-Hodgkin \200\231s lymphoma. Other hematological malignancies, including Burkitt \200 \231s lymphoma, CLL, Waldenstrom \200\231s macroglobulinaemia. Post-transplant lymphoprolif erative disorder (PTLD) without evidence of allograft rejection. Acquired hemophilia. Throm botic thrombocytopaenic purpura. Idiopathic thrombocytopaenic purpura. Rheumatoid arthritis not responding to anti-TNF therapy. Other autoimmune conditions, including SLE. Multifocal motor neuropathy. \200 \200 \200 \200 \200 Routes \200 IV infusion. Adverse effects \200 Pulmonary events (hypoxaemia, pulmonary in \201 ltrates, acute respiratory failure). Hepat itis B reactivation. Tumor lysis syndrome. Severe mucocutaneous reactions (e.g. Stevens \200\223Johnson syndrome). Abdominal pain, bowel obstruction, and perforation. Neutropaenia and thrombocytopaenia. Reactivation of JC virus resulting in progressive multifocal leukoe ncephalopathy. Arrhythmias. Infusion-related syndrome with hypotension, rigors, pyrexia, ur ticaria, angioedema, and bronchospasm. \200 \200 \200 \200 \200 \200 RITUXIMAB 335 See also: Clotting disorders, p470; Platelet disorders, p478; Rheumatic disorders, p572; Va sculitis, p574; Leukemia/lymphoma, p630. This page intentionally left blank 337 Chapter 21 Resuscitation Basic resuscitation 338 Cardiac arrest 340 Fluid challenge 342 338 CHAPTER 21 Resuscitation Basic resuscitation In any severe failure of the cardiorespiratory system, the order of pri ority should be to secure the airway, maintain respiration (manual ventilation if necessary ), restore the circulation (with external cardiac massage if necessary), and consider mecha nical ventilation. Initial assessment should include airway patency, palpation of pulses, m easurement of blood pres- sure, presumptive diagnosis, and consideration of treatment of th e cause. Airway protection The airway should be opened by tilting the head back with one hand on the forehead and lifting the chin with the \201 ngers of the other hand. If there is a neck injury or an inadequate airway with the head tilt and chin lift, a jaw thrust should be per formed. The \201 ngers should be placed behind the angle of the mandible on both sides, a nd the mandible lifted forward and upward until the lower teeth (or gum) are in front of th e upper teeth (or gum). The mouth and pharynx should be cleared by suction and loose \201 tting dentures removed. If necessary, an oropharyngeal (Guedel) airway may be inserted. Manual ventilation Once the airway is protected the patient who is not breathing requires m anual ventilation with a self-in \202 ating bag and mask (Ambu bag). Oxygen should be deli vered in high concentration (FIO2 1.0 for manual ventilation, FIO2 0.6 \200\2231.0 for spon taneously breathing patients) to achieve adequate arterial oxygen saturation. Hyperoxia sho uld not be allowed to persist as this can be detrimental. If the patient breathes inadequat ely (poor arte- rial saturation, hypercapnia, rapid shallow breathing), ventilatory support should continue. Circulation If pulses are impalpable or weak, or if the patient has a severe bradycardia, e xternal cardiac massage is required and treatment should continue as for a cardiac arrest. Hypotension should be treated initially with a \202 uid chal- lenge although life-threate ning hypotension may require blind treatment with epinephrine 0.05 \200\2230.2mg IV increme nts at 1 \200\2232min intervals until a satisfactory blood pressure is restored. Such treat ment should not be pro- longed without circulatory monitoring to ensure the adequacy of car diac output as well as correction of hypotension. Venous access Venous access must be secured early during basic resuscitation. Large- bore c annulae are necessary, e.g. 14G. In cases of hemorrhage, two can- nulae are required. Small peripheral veins should be avoided; forearm \202 exure veins are appropriate if nowhere else is available. In very dif \201 cult patients, a Seldinger approach to the femoral vei n or a central vein may be appropriate. The latter has the advantage of providing central v enous monitoring. BASIC RESUSCITATION 339 See also: Oxygen therapy, p38; Airway maintenance, p40; Endotracheal intubation, p42; Venti latory support \200\224indications, p44; Electrical cardioversion, p94; Central venous cath eter \200\224insertion, p168; Colloids, p246; Inotropes, p264; Vasopressors, p268; Cardiac arrest, p340; Fluid challenge, p342. 340 CHAPTER 21 Resuscitation Cardiac arrest As with basic resuscitation, the order of priority is airway, breathing, cir - culation, and drug treatment. If cardiac arrest is witnessed, a precordial thump may reve rt ventricular tachycardia or \201 brillation. Initial manage- ment of airway and breathi ng is as described for basic resuscitation. Only attempt intubation after adequate pre-oxyg enation. If intubation is dif \201 cult, maintain manual ventilation with an Ambu bag, mas k, and 100% O2. Therapeutic hypothermia is useful to improve cerebral outcome, post- cardiac arrest (particularly out-of-hospital VF or pulseless VT). Cardiac massage External massage provides minimal circulatory support during cardiac arrest . A rate of 100/min with a compression depth of 5cm is recom- mended. Once an arti \201 ci al airway is established, give manual breaths at a rate of 8 \200\22310/min. Compressions s hould not be paused for ventilation. Cardioversion Cardioversion is performed urgently if VT or VF cannot be excluded. Restart c ardiac massage immediately without waiting to review the ECG. Cerebral damage continues whi le there is no blood \202 ow. Drugs Few drugs are necessary for \201 rst-line cardiac arrest management. Drugs should b e given via a large vein since vasoconstriction and poor \202 ow delay peripheral injecti ons reaching the central circulation. If early venous access cannot be secured, the intraos seous route may be used, or double or triple doses of epinephrine may be given via the endo tracheal tube. Epinephrine The A constrictor effects predominate during cardiac arrest, helping to maintai n diastolic blood pressure, and coronary and cerebral perfusion. Irrespective of rhythm giv e 1mg (10mL of 1:10000 solution) every 3 \200\2235min. Vasopressin A recent trial comparing vasopressin and epinephrine showed improved outcomes w ith vasopressin in asystole. The vasopressin dose is 40IU, and may be repeated after 3min i f the \201 rst dose is ineffective. Magnesium A dose of 8mmol can be given in refractory VF, torsades de pointes, hypo- magnesa emia, or if digoxin toxicity is suspected. Atropine A single 3mg dose is given early in asystole or pulseless bradycardia. Amiodarone If VF/VT persists after three shocks, give amiodarone 300mg IV bolus. Calcium chloride Used in pulseless electrical activity if there is hyperkalaemia, hypocal- caemia, or calcium antagonist use. Give 10mL 10% solution. Bicarbonate Only used if cardiac arrest is due to hyperkalaemia or tricyclic poisoning. A d ose of 50mL of 8.4% solution is given. CARDIAC ARREST 341 Key papers The Hypothermia after Cardiac Arrest Study Group. (2002) Mild therapeutic hypoth ermia to improve the neurologic outcome after cardiac arrest. N Engl J Med 346: 549 \200 \22356. Wenzel V for the European Resuscitation Council. (2004) Vasopressor during CPR study. A com - parison of vasopressin and epinephrine for out-of-hospital cardiopulmonary resuscitation. N Engl J Med 350: 105 \200\22313. The European Resuscitation Council (ERC). (2005) Guidelines for Resuscitation 2005. Resusci tation 67S1: S1 \200\223S189. See also: Electrical cardioversion, p94; Therapeutic hypothermia, p100; ECG monitoring, p16 2; Sodium bicar- bonate, p244; Inotropes, p264; Vasopressors, p268; Basic resuscitation, p3 38. 342 CHAPTER 21 Resuscitation Fluid challenge Treat hypovolaemia urgently to avoid the serious complication of multi- org an failure. Ensure an adequate circulating volume before considering other methods of circu latory support. Clinical signs of hypovolaemia (reduced skin turgor, low CVP, oliguria, tac hycardia, and hypotension) are late indicators. Lifting the legs of a supine patient and wa tching for an improvement in the circulation is a useful indicator of hypovolaemia. A high index of suspicion must be maintained; normal heart rate, BP, and CVP do not exclude hypovo laemia The CVP is particularly unreliable in pulmonary vascular disease, right ventricular disease, isolated left ventricular failure, and valvular heart disease. The absolute CVP or PAWP are also dif \201 cult to interpret since peripheral venoconstriction may maintain C VP despite hypovolaemia; indeed, CVP may fall in response to \202 uid. The response to a \202 uid challenge is the safest method of assessment. Choice of \202 uid The aim of a \202 uid challenge is to produce a signi \201 cant (20 0mL) and rapid increase in plasma volume. Colloid \202 uids are ideal; a gelatin solution is recommended for short-term plasma volume expansion in simple hypo- volaemia. Consider h ydroxyethyl starch when there is a probability of cap- illary leak. Packed red cells have a high haematocrit and do not adequately expand the plasma volume. Crystalloid \202 uids a re rapidly lost from the circulation and give a less reliable increase in plasma volume. Assessing the response to a \202 uid challenge Ideally, the response of CVP, PAWP or, pre ferably, stroke volume should be monitored during a \202 uid challenge. Fluid challenges should be repeated if the response suggests continuing hypovolaemia. However, if such moni- toring is not available, it is reasonable to assess the clinical response to up to two \202 uid challenges (200mL each). CVP (or PAWP) response The change in CVP/PAWP after a 200mL \202 uid challenge depends on the starting blood volume (see \201 gure opposite). A \211 3mmHg rise in CVP/ PAWP repr esents a signi \201 cant increase and suggests an adequate circu- lating volume. A positiv e response may sometimes occur in the vasocon- stricted patient with a lower blood volume. It is also important to assess clinical response; if inadequate, it may be appropriate to m onitor stroke volume before further \202 uid challenges or considering further circulator y support (see \201 gure 21.1.). Stroke volume response In the inadequately \201 lled left ventricle, a \202 uid challen ge will increase stroke volume. Failure to increase stroke volume may be due to a well- \201 lled ven- tricle (usually accompanied by a \211 3mmHg rise in \201 lling pressure), ongoing rapid \202 uid loss (e.g. massive hemorrhage), right heart failure or obstruc- t ion (e.g. pericardial tamponade, massive PE, mitral stenosis). It is impor- tant to monitor stroke volume rather than cardiac output during a \202 uid challenge. If the heart rate falls appropriately in response to a \202 uid chal- lenge, the cardiac output may not inc rease despite an increase in stroke volume (see \201 gure 21.1). FLUID CHALLENGE 343 CVP/PAWP >3mmHg 3mmHg <3mmHg Blood volume Stroke volume Blood volume Under filled Well filled Over filled Fig. 21.1. CVP and stroke volume response to \202 uid challenge. See also: Central venous catheter \200\224insertion, p168; Central venous catheter \200\224 use, p170; Cardiac output \200\224central thermodilution, p178; Cardiac output \200\224peri pheral thermodilution, p180; Cardiac output \200\224indicator dilution, p182; Cardiac outpu t \200\224Doppler ultrasound, p184; Cardiac output \200\224 pulse contour analysis, p186; C ardiac output \200\224other techniques, p188; Pressure and stroke volume variation, p190; E chocardiography, p192; Colloids, p246; Basic resuscitation, p338. This page intentionally left blank 345 Chapter 22 Respiratory disorders Dyspnoea 346 Airway obstruction 348 Respiratory failure 350 Atelectasis and pulmonary colla pse 352 Chronic air \202 ow limitation 354 Acute chest infection (1) 356 Acute chest infec tion (2) 358 Acute respiratory distress syndrome (1) 360 Acute respiratory distress syndrom e (2) 362 Asthma \200\224general management 364 Asthma \200\224ventilatory management 366 P neumothorax 368 Haemothorax 370 Haemoptysis 372 Inhalation injury 374 Pulmonary embolus 376 346 CHAPTER 22 Respiratory disorders Dyspnoea De \201 ned as dif \201 culty in breathing. The respiratory rate may be increase d or decreased though the respiratory effort is usually increased with the use of accessory muscles. The patient may show signs of progressive fatigue and impaired gas exchange. Common ICU causes Respiratory Respiratory failure Circulatory Heart failure, hypoperfusion, pulmonary embolus, severe anemia Metabolic Acidosis Central Stimulants, e.g. aspirin Anaphylactic Upper airway obstruction, bronchospasm Psychiatric Hysterical A psychiatric cause of dyspnoea is only made after exclusion of other treatable causes. Dua l coexisting pathologies should be considered, e.g. chest infection and hypovolaemia. Principles of management 1. O2 therapy to maintain SaO2 (ideally 92 \200\22398%). 2. Correc t abnormality where possible. 3. Support therapy until recovery. \200\224Mechanical, e.g. positive pressure ventilation, CPAP. \200\224Pharmacological tre atment, e.g. bronchodilators, vasodilators. 4. Relieve anxiety. DYSPNOEA 347 See also Airway obstruction, p348; Respiratory failure, p350; Asthma \200\224general manage ment, p364; Pilmonary embolus, p376; Heart failure \200\224assesment, p392; Anemia, p472; S ickle cell disease, p474; Metabolic acidosis, p502. 348 CHAPTER 22 Respiratory disorders Airway obstruction Causes \200 \200 \200 In the lumen, e.g. foreign body, blood clot, vomitus, sputum plug. In the wall, e.g. epiglo ttitis, laryngeal oedema, anaphylaxis, neoplasm. Outside the wall, e.g. trauma (facial, nec k), thyroid mass. Presentation \200 \200 In spontaneously breathing patient: stridor, dyspnoea, fatigue, cyanosis. In ventilated pat ient (e.g. due to intraluminal obstruction): raised airway pressures, decreased tidal volum e, hypoxaemia, hypercapnia. Diagnosis \200 \200 \200 Chest and lateral neck X-ray. Fibreoptic laryngoscopy/bronchoscopy. CT scan. Management Presentation outside ICU/operating theater 1. High FIO2. 2. If collapsed or in e xtremis: perform immediate orotracheal intubation. If impossible, emergency cricothyroidotomy or tracheostomy. 3. If symptomatic but not in extremis: consider cause and treat as ap- propriate, e.g. remo val of foreign body. Elective intubation or tracheos- tomy may be required. 4. With acute epiglottitis, the use of a tongue depressor or nasendoscopy may precipitate c omplete obstruction so this should be undertaken in an operating theater ready to perform e mergency tracheostomy. The responsible organism is usually H. in \202 uenzae. Treat early with chloram- phenicol. Acute epiglottitis is recognized in adults. 5. Consider Heliox (79% He/21% O2) alone or as a supplement to oxygen to reduce viscosity and improve air \202 ow. Presentation within ICU/operating theater If intubated: \200 High FIO2. \200 Pass sucti on catheter down the ET tube, assess ease of passage and the contents suctioned. If ET tube is patent, attempt repeated suction interspersed with 5mL boluses of 0.9% saline. Urgent \201 breoptic bronchoscopy may be necessary for diagnosis and, if possible, removal of a f oreign body. If a foreign body cannot be removed by \201 breoptic bronchoscopy, urgent ri gid bronchoscopy should be performed by an experienced operator. If the ET tube is obstruct ed, remove the tube, oxygenate by face mask, then reintubate. If not intubated: \200 \200 As for out-of-ICU presentation. If recently extubated, consider laryngeal oedema. Post-extu bation laryngeal oedema is unpredictable though occurs more commonly after prolonged or rep eated intubation; the incidence may be reduced by proper tethering of the endotracheal tube and prevention of excessive coughing. Diagnosed by nasendoscopy. Dexamethasone 4mg x3 dose s over 24h may reduce the swelling though re-intubation is often necessary in the interim. AIRWAY OBSTRUCTION 349 See also Endotracheal intubation, p42; Continuous positive airway pressure, p70; Tracheotom y, p80; Fibreoptic bronchoscopy, p88; Corticosteroids, p328. 350 CHAPTER 22 Respiratory disorders Respiratory failure De \201 ned as impaired pulmonary gas exchange leading to hypoxaemia a nd/ or hypercapnia. Common ICU causes Central Cerebrovascular accident, drugs (e.g. opiates, sedatives), raised intracranial pressure, tr auma Brainstem/spinal cord Trauma (at or above phrenic level), tetanus, Pickwickian syndrome, motor neuron disease Neuropathy Guillain \200\223Barr , critical illness polyneuropathy Neuromuscular Muscle relaxants, organophosphorus poisoning, myasthenia gravis Chest wall/muscular Flail chest, heart failure, myopathy (including critical illness and disuse myopathy) Airways Upper airways obstruction, airway disruption, asthma, anaphylaxis Parenchymal Pneumonia, ARDS, \201 brosis, pulmonary oedema Extra-pulmonary Pneumothorax, pleural effusion, haemothorax Circulatory Pulmonary embolus, heart failure, Eisenmenger intracardiac shunt Types of respiratory failure \200 \200 Type I: hypoxaemic \200\224often parenchymal in origin. Type II: hypoxaemic, hypercapnic \200\224often mechanical in origin. Principles of management 1. Ensure SaO2 is compatible with survival (i.e. usually >80%, pre ferably >92 \200\22398%). 2. Correct abnormality where possible, e.g. drain pneumothorax, relieve/ bypass obstruction. 3. Support therapy until recovery: \200\224Positive pressure ventilation. \200\224Non-inv asive respiratory support. \200\224Pharmacological treatment, e.g. bronchodilators, antibi otics. \200\224Opiate antagonists, respiratory stimulants. \200\224General measures, e.g. hydration, airway humidi \201 cation. \200\224Removal of secretions, physiotherapy, bron choscopy. 4. Unless the patient is symptomatic (e.g. drowsy, dyspnoeic), the PaCO2 may be l eft elevated to minimize ventilator trauma (permissive hyper- capnia) or if chronically hyp ercapnic (type II respiratory failure). RESPIRATORY FAILURE 351 See also: Oxygen therapy, p38; Bronchodilators, p254; Respiratory stimulants, p256; Antimic robials, p326; Corticosteroids, p328; Airway obstruction, p348; Atelectasis and pulmonary c ollapse, p352; Chronic air \202 ow limitation, p354; Acute chest infection (1), p356; Acut e respiratory distress syn- drome (1), p362; Asthma \200\224general management, p364; Pneum othorax, p368; Inhalation injury, p374; Pulmonary embolus, p376; Heart failure \200\224asse ssment, p392; Stroke, p452; Guillain \200\223Barr syndrome, p456; Myasthenia gravis, p458 ; Critical care neuromuscular disorders, p460; Tetanus, p462; Botulism, p464; Poisoning \200\224general principles, p520; Sedative poisoning, p526; Tricyclic anti- depressant pois oning, p528; Organophosphate poisoning, p540; Systemic in \202 ammation/multi-organ failur e \200\224causes, p556; HIV related disease, p566; Multiple trauma (1), p582; Multiple trau ma (2), p584; Head injury (1), p586; Head injury (2), p588; Spinal cord injury, p590; Blast injury, p596; Near-drowning, p610; Post-operative critical care, p620. 352 CHAPTER 22 Respiratory disorders Atelectasis and pulmonary collapse A collapsed lobe or segment is usually visible on a ches t X-ray. Macroatelectasis is also evident as volume loss. In microatelectasis, the chest X- ray may be normal, but the A \200\223aDO2 will be high. Atelectasis reduces lung compliance and PaO2, and increases work of breathing. This may result in poor gas exchange, increased airway pressures, reduced tidal volume and, if severe, circulatory collapse. Causes \200 Collapsed lobe/segment \200\224bronchial obstruction (e.g. sputum retention, foreign body, blood clot, vomitus, misplaced endotracheal tube). Macroatelectasis \200\224air space compr ession by heavy, oedematous lung tissue, external compression (e.g. pleural effusion, haemo thorax), sputum retention. Microatelectasis \200\224inadequate depth of respiration, nitrog en washout by 100% oxygen with subsequent absorption of oxygen occurring at a rate greater than replenishment. Sputum retention Excess mucus (sputum) normally stimulates coughing. If ciliary clearance i s reduced (e.g. smoking, sedatives) or mucus volume is excessive (e.g. asthma, bronchiectas is, cystic \201 brosis, chronic bronchitis), sputum reten- tion may occur. Sputum retenti on may also be the result of inadequate coughing (e.g. chronic obstructive pulmonary diseas e, pain, neuromus- cular disease) or increased mucus viscosity (e.g. hypovolaemia, inadequa te humidi \201 cation of inspired gas). Preventive measures \200 Sputum hydration \200\224maintenance of systemic hydration and humidi \201 cation of inspi red gasses (e.g. nebulised saline/bronchodilators, heated water bath, heat-moisture exchang ing \201 lter). Cough \200\224requires inspiration to near total lung capacity, glottic c losure, contraction of abdominal muscles, and rapid opening of the glottis. Dynamic compres sion of the airways and high velocity expiration expels secretions. The process is limited if total lung capacity is reduced, abdominal muscles are weak, pain limits contraction, or small airways collapse on expiration. It is usual to \202 ex the abdomen on coughing, and this should be simulated in supine patients by drawing the knees up. This also limits pain in patients with an upper abdominal wound. Physiotherapy \200\224postural drainage, percus sion and vibration, hyperin \202 ation, intermittent positive pressure breathing, incentiv e spirometry, or manual hyperin \202 ation. Maintenance of lung volumes \200\224increased VT, CPAP, PEEP, positioning to reduce compression of lung tissue by oedema. Management Speci \201 c management depends on the cause and should be corrective. All meas ures taken for prevention should continue. If there is lobar or segmental collapse with obs truction of proximal airways, bronchoscopy may be useful to allow directed suction, foreign body removal, and saline instillation. Patients with high FIO2 may deteriorate due to the effects of excessive lavage or suction reducing minute ventilation. ATELECTASIS AND PULMONARY COLLAPSE 353 See also: Fibreoptic bronchoscopy, p88; Chest physiotherapy, p90; Bronchodilators, p254; Ch ronic air \202 ow limitation, p354; Acute weakness, p440; Critical care neuromuscular diso rders, p460; Pain, p618; Post-operative critical care, p620. 354 CHAPTER 22 Respiratory disorders Chronic air \202 ow limitation Many patients requiring ICU admission for community-acquire d pneu- monia have chronic respiratory failure. An acute exacerbation (which may or may not be infection-related) results in decompensation and sympto- matic deterioration. Such infe ctions include viruses, Haemophilus in \202 u- enzae, Klebsiella, and Staphylococcus aureu s, in addition to Streptococcus pneumoniae, and rarely, Mycoplasma pneumoniae and Legionell a pneu- mophila. Otherwise, patients are admitted with coincidental chronic air \202 ow li mitation (CAL) or as a prophylactic measure in view of their limited respiratory function, e.g. for elective post-operative ventilation. Problems in managing CAL patients on the ICU \200 \200 Disability due to chronic ill health. Fatigue, muscle weakness, and decreased physiological reserve leading to earlier need for ventilatory support, increased dif \201 culty in wean ing, and greater physical dependency on support therapies. Psychological dependency on supp ort therapies. More prone to pneumothorax. Usually have greater levels of sputum production . Right ventricular dysfunction (cor pulmonale). \200 \200 \200 Notes \200 Trials of non-invasive ventilatory support 9 respiratory stimulants such as doxepram have s hown considerable success in avoiding intubation and mechanical ventilation. Decisions on w hether or not to intubate should be made in consultation with the patient (if possible), th e family, and a respiratory physician or GP with knowledge of the patient. The patient shou ld be given the bene \201 t of the doubt, and intubated in an acute situation where a prec ise history and quality of life are not known. Accept lower target levels of PaO2 or SpO2 ( e.g. 88 \200\22392%). Accept higher target levels of PaCO2 if patient is known or suspected to have chronic CO2 retention (e.g. elevated plasma bicarbonate levels on admission to hos pital). \200 Weaning the patient with CAL \200 \200 An early trial of extubation may be worthwhile. Weaning may be a lengthy procedure. Daily t rials of spontaneous breathing may reveal faster-than-anticipated progress. Provide plentif ul encouragement and psychological support. Setting daily targets and early mobilization ma y be advantageous. Do not tire by prolonged spontaneous breathing. Consider gradually incre asing periods of spontaneous breathing interspersed by periods of rest. Ensure a good night \200\231s sleep, ideally by natural means. Use patient appearance and lack of symptoms (e. g. tachypnoea or fatigue) rather than speci \201 c blood gas values to judge duration of s pontaneous breathing. Early tracheostomy may bene \201 t when dif \201 culty in weaning i s expected. The patient may cope better with a tracheostomy mask than CPAP. Extrinsic PEEP or CPAP may prevent early airway closure reducing the work of breathing. However, there is a risk of air trapping. Consider heart failure as a cause of dif \201 culty in weaning. \200 \200 CHRONIC AIRFLOW LIMITATION 355 Key papers Brochard L, Mancebo J, Wysocki M, et al. (1995) Non-invasive ventilation for acu te exacerbations of chronic obstructive pulmonary disease. N Engl J Med 333: 817 \200\22322 . Antonelli M, Conti G, Rocco M, et al. (1998) A comparison of non-invasive positive-pressure ven- tilation and conventional mechanical ventilation in patients with acute respiratory f ailure. N Engl J Med 339: 429 \200\22335. Epstein SK, Ciubotaru RL. (1998) Independent effects of etiology of failure and time to rei ntuba- tion on outcome for patients failing extubation. Am J Respir Crit Care Med 158: 489 \200\22393.