Oxygen Environmental hypoxia occurs due to the consumption of oxygen during combustion. Toxins Toxins causing direct damage to the epithelium of the airways include sulfur dioxide , nitrogen dioxide, chlorine and ammonia. Their effects result from pH or free radical dama ge. Distal carriage can occur in the presence of carbon particles. Increased alveolar capil lary permeability and lung water contribute to decreased lung compliance. Epithelial cast f ormation and sloughing, mucociliary dysfunction and oedema result in increased airway resis tance, airway obstruction, atelectasis and predisposition to bacterial overgrowth and the d evelopment of pneumonia. Ventilation \200\223 perfusion mismatch with increased pulmonary s hunt results. Systemic toxins include the asphyxiants carbon monoxide, hydrogen cyanide and hydrogen sul \201 de. These bind to mitochondrial cytochromes causing disruption of the e lec- tron transportation chain. Carbon monoxide has a higher af \201 nity for hemoglobin t han oxygen, preventing binding of the lat- ter and impairing oxygen carriage. Other systemi c toxins include hydrocarbons, organophosphates and metal fumes. Monitoring Vital signs should be monitored continuously during the assessment and initial m anagement phase. Pulse oximetry can give erroneously high readings in the presence of signi \201 cant carboxyhaemoglobin. Speci \201 c investigations Arterial blood gas analysis wi th co-oximetry is essential to assess carboxyhaemoglobin levels. Blood should be drawn for cyanide levels; however, the results may take several days to be ascertained. Cyanide toxic ity should be suspected and treated in patients with persistent high blood lactate levels, acidaemia, high mixed venous oxygen saturation, low oxygen extraction ratio and deteriorati ng neurological and cardiac function despite appropriate resuscitation. Corrected anion gap and osmolar gap should be calculated if acidaemia persists. Toxicology screen should be co nsidered, 273 CHAPTER 17.13 Inhalation injury Cardiovascular support primarily involves \202 uid resuscita- tion. This can be extremely dif \201 cult to assess, particularly if large burns co-exist. Widespread increases in ca pillary permeability result in \202 uid redistribution into the intersti- tium, including that of the lung and airway. Patients with major burns and inhalation injury require far g reater \202 uid resuscitation than those with either injury alone. Limitation of \202 u id resuscitation in victims of smoke inhalation has not been supported in clinical trials. Crystalloid resuscitation for the \201 rst 24h is based on historic evidence, but its use in preference to colloids and blood should be balanced against other injuries. New colloid s are available and in development which may alter the recommended \202 uid resuscitation regimes. Lung injury is a trigger of SIRS and multiple organ dysfunction. Inotrope and vas opressor therapy may be required. Adrenal insuf \201 ciency should be considered in patien ts refractory to vasopressor therapy, and replacement therapy commenced if appropriate. Imp rovement in cardiac output and blood pressure may enhance oxygenation through improved lung perfusion and reduced intrapulmonary shunt. Hypoxic pulmonary vasoconstriction combined wi th increased thromboxane release following smoke inhalation may result in pulmonary hyperte nsion and RV dysfunction. particularly in patients with reduced or inconsistent neuro- logical levels. Bronchoscopic examination is useful in assessing the tra- cheobronchial tree of patients who are stable a nd have undergone endotracheal intubation. It can be combined with therapeutic lavage CXR s igns may lag behind the clinical course of the patient. A normal chest radiograph does not exclude signi \201 cant, early inhalation injury. Management Initial management Attention to airway, breathing and circulatory abnormali- tie s forms the central tenet of initial management. Airway swelling and obstruction is progres sive, and may be exacerbated during \202 uid resuscitation, emphasizing the need for cons tant reassessment. High \202 ow humidi \201 ed oxygen should be administered to all pati ents in the \201 rst instance. If airway compromise is anticipated, expert endotracheal i ntubation should be performed with prior preparation for dif \201 cult or failed intubatio n. Respiratory management should focus on oxygen delivery. Inhalation injury commonly trigg ers ALI and ARDS; however, this may develop insidiously over a period of hours or days. If mechanical ventilation is required, standard recruitment and lung protection measures shoul d be employed. High frequency oscillatory ventilation has been associated with improved out come and reduced incidence of pneumonia. Early bronchoscopy is recommended to record level and degree of injury. Lavage should be per- formed if pulmonary contamination is present; h owever, consideration should be given to the fact that excessive saline lavage may induce l ung injury. Regular administration of aerosolized bronchodilators should be considered. Neb ulized heparin and NAC have been used to reduce cast formation, distal airway obstruc- tion and atelectasis. Antibiotic and steroid therapies have no proven prophylac- tic role but m ay be required in speci \201 c situations. Pneumonia is the most common cause of death in hospitalized patients suffering from inhalation injury. Carboxy-Hb levels >10% should be tr eated with 100% inspired oxygen therapy. The half-life of carboxy-Hb is reduced from 240min at an inspired oxygen concentration (FiO2) of 21% to 80min at an FiO2 of 100%. Hyperbaric therapy should be considered in patients with carboxy-Hb >40%, or 20% if pregnant and in p atients who have had lowered conscious level from no other cause. Suspicion of cyanide pois oning (see above) should prompt empiric treatment. Sodium thiosulfate acts slowly by cata- lysing the metabolism of cyanide. Sodium nitrite reduces cyanide binding by oxidation of he moglobin to methaemo- globin. Methaemoglobin levels of 40% should be targeted. Cyanide-bin ding agents such as dicobalt edetate or hydrox- ycobalamin may be used, though the former m ay induce cardiac arrhythmias and instability if used in the absence of cyanide poisoning. Longer term management considerations Chest physiotherapy remains widely accepted manage- m ent despite a lack of evidence to support it. Tracheostomy should be considered in patients requiring long-term mechanical ventilation or pulmonary toilet. ALI and ARDS from any caus e is associated with increased resting energy expenditure; dramatically so if burns are als o present. Careful attention to nutritional management should be considered at an early sta ge and reviewed continuously. Therapies employed in the management of long-term critically ill and mechanically ventilated patients should be considered. Examples include the use of prophylaxis against venous thromboembolism and GI stress ulceration. Further reading Enkhbaatar P, Traber DL. Pathophysiology of acute lung injury in combined b urn and smoke inhalation injury. Clin Sci 2004; 107: 137 \200\22343. Freitag L, Long WM, Kim CS, et al. Removal of excessive bronchial secretions by asymmetric high-frequency oscillations. J Appl Physiol 1989; 67: 614 \200\2239. Heimbach DM, Waeckerle JF. Inhalation injuries. Ann Emerg Med 1988; 17: 1316. Herndon DN, Barrow RE, Traber DL, et al. Extravascular lung water changes following smoke i nhalation and massive burn injury. Surgery 1987; 102: 341 \200\2239. Herndon DN, Tranber DL, Traber LD. The effect of resuscitation on inhalation injury. Surgery 1986; 100: 248 \200\22351. Orzel RA. Toxicological aspects of \201 resmoke: polymer pyrolysis and combustion. Occup Med 1993; 8: 414 \200\22329. Ware LB, Matthay MA. The acute respiratory distress syndrome. N Engl J Med 2000; 342: 1334 \200\22349. 274 J DARROUJ & P DELLINGER Pulmonary embolism Pulmonary thromboembolism embolism (PE) is de \201 ned as a migration of a clot to the pul monary circulation causing compromised or obstructed \202 ow. Hypoxaemia, shock and death are potential results in massive PE. Physical \201 ndings Tachycardia and tachypnoea are the most common signs. More speci \201 c physical exam \201 ndings include right sided S3 sound, wildly split second sound, murmur of tricuspid regurgitation and an accentuated S2 closure sound. Fever of >100.0 F is present in 14% of patients with angiographi- cally proven PE and no source of fever. It is rarely more than 101.0 F. Pathophysiology Clinically significant PE comes from deep veins, most commonly from femoral or Iliac veins and less likely from pelvic or the inferior vena cava. CVCs can induce deep venous thrombosis (DVT). Untreated, calf vein thrombi may extend into the popliteal and fe moral veins, causing proximal DVT and PE. This is unlikely to occur when asymptomatic popli teal clot is discovered in patients who are progressively ambulating after surgery. PE caus es hypoxaemia by inducing atelectasis (depletion of surfactant), bronchoconstriction secret ion and reperfusion injury to the endothelial \200\223epithelial barrier. Massive PE produc es signi \201 cant dead space with elevation of PaCO2 and the potential for severe pulmona ry artery hypertension-induced right to left shunt through a patent foramen ovale. The morb idity and mortality of PE are almost always due to additional emboli following initial diag nosis. CXR CXR usually is normal, but can show enlarged heart, pleural effusion, Westermark sign ( dilatation of pulmonary artery proximal to the emboli with sharp cut-off), pulmonary in \201 l- trates, elevated hemidiaphragm and atelectasis. Pulmonary infarction can manifest a s wedge- shaped pulmonary in \201 l- trates on chest radiograph. ECG ECG \201 ndings including tachycardia and non-speci \201 c ST-T elevation lack speci \201 city, with more speci \201 c \201 ndings being signs of RV strain such as P pulmo nale, S1Q3T3, right bundle branch block or right axis deviation. Echocardiogram signs of ac ute pulmonary artery hyper- tension include right heart dilation, tricuspid regurgitation, pulmonary artery dilation, loss of respiratory variation in vena cava diameter, and interve ntricular septum bulge into the LV. Acute RV dilation with hypokinesis sparing the apex is the characteristic \201 nding. Risk factors Venous stasis, activation of blood coagulation, and vascular damage (Virchow \200\231s triad). The most common clinically identi \201 able risk factors are: previous h istory of DVT or PE, prolonged immobilization, underlying malignancy, paralysis and recent surgery or pregnancy. Further investigation Patients with low pre-testing clinical probability of PE Normal quant itative D-dimer in the low to intermediate risk patients measured by ELISA probably rules o ut PE especially in the emergency department. If D-dimer is positive, multidetector CT angi ogram (CTA)/CT venogram (CTV) of femoral and popliteal veins is recommended. If negative, t here is no need for fur- ther intervention. Based upon location and certainty of the clot, additional testing may be necessary due to increased false-positive results in this group. Across all risk categories, CTA/CTV has a sensitivity of 90% and speci \201 - city of 95%. Diagnosis Clinical presentation depends upon the size, location, number of emboli and the p atient \200\231s underlying cardiorespi- ratory reserve. The classic triad of chest pain, h aemoptysis and dyspnoea is present in <20% of patients. 97% of patients with PE have at lea st one of the following: pleuritic chest pain, dyspnoea or respiratory rate >20/min. Chest pain can be reproducible. Table 17.14.1 Well \200\231s criteria for pulmonary embolism Patients with intermediate pre-testing clinical probability 29 \200\22338% of patients with intermediate clinical probability have PE. PE is present in 8% if CTA is negative. If CTA/ CTV is negative, PE is ruled out, but venous ultrasound is needed if only CTA (without CTV) is used. Clinical features Points Clinical symptoms of DVT Other diagnosis less likely than PE Heart rate >100/min Immobiliza tion or surgery within past 4 weeks Previous DVT or PE Haemoptysis 3 3 1.5 1.5 1.5 1 Patients with high clinical probability If CTA is negative in a patient with a high probabi lity clinical assessment, PE may still be present in 40%, while if CTA/ CTV are negative, P E is present in 18%. With negative CTA/ CTV in a high clinical probability setting, a digit al subtrac- tion angiogram (DSA) is useful. Malignancy 1 V/Q scan A normal V/Q scan rules out PE, but a high probability V/Q scan rules in PE in mos t cases. Low or intermediate prob- ability results in V/Q scan in the presence of high clin ical probability warrants further investigation. Risk score interpretation: 6 points indicates high probability of DVT (87.4%) 2 \200\2236 p oints indicates moderate risk (27.8%) <2 points indicates low risk (3.4%). Clinical examina tion is not reliable in diagnosis of either PE or DVT, but applying a pre-test probability score such as Well \200\231s criteria (see Table 17.14.1) may be clinically useful. Diagnostic notes DSA is the gold standard in evaluation for PE 275 CHAPTER 17.14 Pulmonary embolism Blood \202 ow to coronary arteries depends upon the aortic pressure as the upstream press ure. In light of the increased right heart pressures (downstream pressure), it is impor- ta nt to maintain systemic blood pressure to maintain \201 lling of right heart coronary art ery. A combined inotrope/ vasopressor is preferred to maintain blood pressure in massive PE to increase cardiac output and improve oxygen transportation. An IVC \201 lter is indica ted when anticoagulation is contrain- dicated or when thrombolysis would be given but is co ntraindicated. If the initial testing is V/Q lung scanning, leg ultrasound is recommended when: \200 non-diagnostic (low or intermediate probability) lung perfusion scan normal perfusion scan in high clinical probability (high risk patients) or high probability scans in low risk pat ients. CTA/CTV is an option to leg ultrasound in these scenarios leg ultrasound may be used in combination with negative CTA to enhance the negative predictive power. Miscellaneous The healthy RV cannot generate mean pulmonary artery pressure >40mm Hg in an acute situation like PE. The pres- ence of higher pressure re \202 ects pre-existing pulmo nary hypertension. In mechanically ventilated patients, a fall in end-tidal CO2 (ETCO2) mig ht be useful in raising the clinical suspicion of PE, while the decrease in difference betw een PaCO2 and ETCO2 probably indicates an effective thrombolysis. Further reading Buller HR, Agnelli G, Hull RD, et al. Antithrombotic therapy for venous thr omboembolic disease: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy . Chest 2004; 126 (3 Suppl): 401S \200\22328S Davidson B, Karmy-Jones R. When pulmonary embolism treatment isn \200\231t working. Chest 2006; 129: 839 \200\22340. Dellinger RP. Pulmonary thromboembolism in critical care board review. Northbrook, IL: Amer ican College of Chest Physicians, 2007. Treatment Kruip MJ, Leclercq MG, van der JHeul C, et al. Diagnostic strategies for excluding pulmonar y embolism in clinical outcome studies. A systematic review. Ann Intern Med 2003; 138: 941 \200\22351. LMWH is at least as effective as UFH in treating PE. Therapy with heparin for at least 4 \200\2235 days is recommended while the patient is on vitamin K antagonist even if the INR is >2. Intermittent injection of heparin is associated with a higher rate of bleeding than heparin infusion; therefore, it is not recommended. Consider thrombolytics in haemodynami- cally unstable patients (vasopressor requirement). There are not enough data to support rou tine use of thrombolyt- ics in PE complicated with RV dysfunction without haemo- dynamic co mpromise, although it may be appropriate in some scenarios. Thrombolysis failure, which is de \201 ned as persistent RV dysfunction and haemodynamic instability, is expected in 8% o f cases. In this case, rescue surgical embolectomy may lead to a better outcome than repeat ed thrombolysis. In massive PE, infusion of a large amount of \202 uids might have a dele terious effect on the LV function as a result of RV dilation and interventricular shift tow ard LV, causing decreased LV compliance and lowered cardiac output. McConnell MV, Solomon SD, Rayan ME, et al. Regional right ventricular dysfunction detected by echocardiography in acute pulmonary embolism. Am J Cardiol 1996; 78: 469 \200\22373. PIOPED Investigators. Value of the ventilation/perfusion scan in acute pulmonary embolism: results of the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED). JAMA 199 0; 263: 2753 \200\2239. Stein PD, Afzal A, Henry JW, et al. Fever in acute pulmonary embolism. Chest 2000; 117: 39 \200\22342. Stein PD, Woodard PK, Weg JG, et al. Diagnostic pathways in acute pulmonary embolism: recom mendations of the PIOPED II Investigators. Am J Med 2006; 119: 1048 \200\22355. Wiegand UK, Kurowski V, Giannitsis E, et al. Effectiveness of end- tidal carbon dioxide ten sion for monitoring thrombolytic therapy in acute pulmonary embolism Crit Care Med 2000; 28 : 3588 \200\22392. Wood KE. Major pulmonary embolism: review of a pathophysio- logic approa ch to the golden hour of hemodynamically signi \201 cant pulmonary embolism. Chest 2002; 1 21: 877 \200\223905. 276 T PARKE Community-acquired pneumonia Community-acquired pneumonia (CAP) has an overall incidence of 5 \200\22311 per 1000 adults . It is characterized by cough, tachypnoea, sputum production, focal chest signs and eviden ce of systemic sepsis. A CXR will show shadowing in one or more lung segments. About 30% of such patients are admitted to hospital and, of these, 5 \200\22310% require ICU admission. This chapter will deal with severe CAP in adults, and will not include patients in hospita l >10 days, those with acute exacerbations of COPD or patients with severe immunosuppressio n. Urine for pneumococcal C polysaccharide antigen and Legionella antigen testing. This is 95% speci \201 c and 80% sensitive, and is especially useful if antibiotics have been given p rior to cultures being taken. Paired serology testing (on admission and 7 \200\22310 days l ater) for Mycoplasma, Chlamydiae and viruses. Treatment CAP which requires ICU is a severe illness with a high mortality. Treatment consi sts of early administration of appropriate antibiotics, within 8h of admission, and sup- po rtive care. Patients may require ICU for the support of the respiratory system, the circula tion and other organ systems. Etiology Of patients admitted to ICU, the most common organisms isolated are: \200 \200 \200 \200 \200 Streptococcus pneumoniae (22%) Legionella (18%) Viral (10%) Staphylococcus aureus (9%). May complicate in \202 uenza Chlamydia pneumonia. This can be present as a co-patho- gen to S . pneumonia or occur in isolation. Antibiotic therapy In all patient groups S. pneumoniae is the most common pathogen in sever e CAP. Unlike meningitis, penicillin resistance of S. pneumoniae is not an issue in the tre atment of pneumonia, since tissue levels approximate blood levels. Legionella and C. pneumo niae are sensitive to clarithromycin. \200 In 1/3 of cases no organism is isolated. However, the mortality rate of patients with posit ive and negative micro- biology investigations is similar. Clinical and radiological featur es are not helpful in distinguishing between different aetiologies. Patients from nursing h omes are at risk of aspiration pneumonitis. Initial antibiotic therapy should consist of co-amoxiclav 1.2g 8 hourly IV, or cefuroxime 1 .5g 8 hourly IV, plus a macrolide, usually clarithromycin 500mg 12 hourly IV. In patients w ith anaphylactic reactions to -lactams discuss with the local microbiology department. Qu inolones (e.g. levo \202 oxacin 500mg 12 hourly IV) with enhanced pneumococcal activity ar e one option. In con \201 rmed Legionella, treatment is continued with clarithromycin, and rifampicin (600mg 12 hourly IV) can be added. Rifampicin can be considered in severe CAP w hich is failing to improve. Treatment with antibiotics should continue for 10 days, extendi ng to 14 \200\22321 days in cases of legionella, staphylo- cocci or Gram-negative enteric b acilli. Initial management In severe CAP, initial management should follow standard ABCDE assessmen t. The airway should be assessed, and high \202 ow oxygen administered to ensure an oxyge n satura- tion (SaO2) >92%. Signs of respiratory distress, respiratory rate, poor perfusion , shock, focal chest signs and level of consciousness are noted. IV access is established, baseline investigations performed and IV antibiotics commenced (see below). The CURB-65 sco re should be measured. CURB-65 The CURB-65 score is a 6-point scale (0 \200\2235) for assessing severity and risk of death in CAP. One point is given to each of \200 \200 \200 \200 Note that MRSA and Pseudomonas are not covered by this regime \200 The incidence of MRSA is rising in the community, particularly in some nursing homes. The l ocal micro- biology department should be noti \201 ed early if MRSA is suspected. MRSA pne umonia is treated with linezolid 600mg 12 hourly IV (vancomycin has poor lung penetration) Pseudomonas is a rare cause of CAP (<4%). The American Thoracic Society recommends cover in patients with the following four risk factors: bronchiectasis; malnutri- tion; broad-spect rum antibiotics for >7 days within the last month; and chronic steroid therapy (>10mg predn isolone/day). Treatment of Pseudomonas pneumonia is with ceftazi- dime 2g 8 hourly IV plus gentamicin Confusion: new onset confusion (mini-mental test \211 8) Urea: raised urea >7 mmol/l. Resp iratory rate: \211 30 breaths/min Blood pressure: systolic blood pressure <90mm Hg and/ or diastolic blood pressure \211 60mm Hg 65: age \211 65yrs Mortality rates are: score 0, 0.7%; score 1, 3.2%; score 2, 13%; score 3, 17%; score 4, 41. 5%; score 5, 57%. Patients with a score of \211 3 require urgent hospital admission and as sessment for ICU admission. Investigations All patients with severe pneumonia require a CXR, FBC, U&Es, liver function tests (LFTs), CRP, blood gas analysis and lactate. Microbiological investigations required are; \200 Ventilation \200 NIV can produce a transient improvement in oxygen saturation, but >50% of patients subseque ntly require intubation. Patients >40yrs old, and those with a respiratory rate >38 have th e highest failure rates. If NIV or CPAP are undertaken for CAP it should be in an intensive care environment, where invasive ventilation can be under- taken rapidly Blood cultures, ideally before the \201 rst dose of antibiotic, although this should not be delayed. They are positive in 10 \200\22320%. Sputum culture with urgent Gram stain. Int ubated patients should have a broncoalveolar lavage sample taken (blind or bronchoscopic), again with urgent Gram stain. 277 CHAPTER 17.15 Community-acquired pneumonia Lung abscesses are more common in debilitated patients, alcoholics and following aspiration . A variety of organisms may be responsible. Treatment consists of prolonged antibiotics, a nd a surgical opinion. Invasive ventilation should aim at ensuring a safe level of oxygenation (PaO2 >8kPa) whilst minimizing pulmonary barotrauma and volotrauma. Tidal volumes should be set at 6 \200\2237 ml/kg, with plateau pressures \211 30cm H2O. In severe lobar pneumonia, much of the lung m ay not be recruitable. High levels of PEEP can damage normal alveoli and worsen shunt. ARDS can complicate severe CAP and may be more PEEP responsive. Systemic complications \200 Patients with S. aureus or S. pneumoniae may develop metastatic infections, including menin gitis, endocarditis and septic arthritis. Legionella can produce a variety of complications includ- ing encephalitis, pericarditis, pancreatitis, polyarthropa- thy, hyponatraemia, ab normal liver function, thrombocytopaenia, diarrhea and renal failure. Circulation Septic shock worsens the prognosis in CAP, and should be treated with optimal v olume loading and inotropes (noradrenaline dobutamine). In the acute stage (ideally with in 6h) poor organ perfusion (lactate 4mmol/l) and septic shock should be managed as describ ed by Rivers et al. \200 \200 \200 Prognosis The CURB-65 score gives the best early indication of mortality. Mortality is wors ened by the presence of signi \201 - cant co-morbidities, septic shock, and in Pseudomonas pneumonia. CVP >8mm Hg MAP >65mm Hg Central venous saturation of \211 70%. Hydrocortisone 50mg qds for 7 days and activated protein C can be considered. After the ini tial resuscitation, \202 uid management should be more cautious to avoid worsening gas ex change and increasing lung water. Further reading British Thoracic Society Pneumonia Guidelines (2001, updated 2004) http://www.brit-thoracic.org.uk/bts_guidelines_ Complications Parapneumonic effusions and lung abscess Up to 50% of patients with bacterial CAP develop parap- neumonic effusions. \200 pneumonia_html Chiou CCC, Yu VL. Severe pneumococcal pneumonia; new strate- gies for management. Curr Opin Crit Care 2006; 5: 470 \200\2236. Lim WS, Van der Eerden MM, Laing R, et al. De \201 ning community acquired pneumonia sever ity on presentation to hospital; an international derivation and validation study. Thorax 2 003; 58: 377 \200\22382. Effusions should be tapped under ultrasound control. The appearance is noted, and microscop y and culture requested. The pH is measured anaerobically in a blood gas syringe. A complic ated parapneumonic effusion is de \201 ned as clear \202 uid with a pH <7.2. In empyema, the \202 uid is cloudy; frank pus, or organisms are present on Gram stain Both require e ffective pulmonary drainage and, in the case of an empyema, a surgical opinion. Rivers E, Nguye B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001; 345: 1368 \200\22377. Wilkinson M, Woodhead MA. Guidelines for community acquired pneumonia in the ICU. Curr Opin Crit Care 2004; 1: 59 \200\22363. 278 T LISBOA & S RELLO Hospital-acquired pneumonia De \201 nition and epidemiology Hospital-acquired pneumonia (HAP) is de \201 ned as a pne u- monia beginning >48h after hospital admission. It represents the second most common noso comial infection, accounting for >25% of all ICU nosocomial infections. Its incidence is be tween 5 and 15 episodes per 1000 hospital admissions. More than 80% of HAP episodes in ICU are related to mechanical ventilation \200\224VAP. HAP mortality in the ICU may vary from 3 0 to 70% in different series. Several factors such as age, diabetes mellitus, head trauma and coma, local \202 ora and previous exposure to antibiotics Early-onset pneumonia (<5 days) S. pneumoniae Late-onset pneumonia (>5 days) P. aeruginosa H. in \202 uenzae MRSA Acinetobacter baumannii MSSA Pathogenesis For HAP occurrence there must be the entry of pathogens into the lower respira tory tract, followed by colonization, then overwhelming host \200\231s defenses. The balanc e among pathogen virulence, host \200\231s defense and bacterial burden (related to volume of aspiration) is the most important factor for HAP/VAP development. Important mechanisms a ssociated with pathogenesis are: \200 may increase the frequency of speci \201 c pathogens. In VAP patients, a very important is sue is the time of onset of pneumonia. Prevention HAP episodes must be considered preventable until proven otherwise. Prevention o f HAP/VAP episodes constitutes a cornerstone of optimal clinical practice on ICU. The appli cation of a bundle of evidence-based interven- tions (care bundlles) has demonstrated reduc tion in pneumonia incidence. The main evidence-based interven- tions are: \200 Aspiration of oropharyngeal pathogens and leakage of bacteria around the cuff of tracheal t ube (>90% of episodes) Colonization of tracheal tube (bio \201 lm) Condensate on ventilato r circuits, nebulizer and humidi- \201 ers Inhalation or direct inoculation of pathogens into the lower airway Haematogenous spread (uncommon). \200 No ventilatory circuit tube changes unless speci \201 cally indicated Hand hygiene Appropr iatelly educated and trained staff Daily interruption of sedation Reduce duration of intuba tion and of mechanical ventila- tion through an improvement on sedation management and earl y weaning Oral hygiene with chlorhexidine Control endotracheal cuff pressure at least every 24h Infection control measures Avoid intubation and reintubation as possible Semi-recumben t position (30 \200\22345 ) \200 \200 \200 Risk factors The risk factors for HAP include patient characteristics and infection control -related problems. The main risk factor is intubation and mechanical ventilation, increasin g the risk of HAP 6- to 21-fold. \200 \200 \200 \200 Severe acute or chronic illness Immunocompromise Hypotension Advanced age Coma Alcoholism Diagnosis HAP diagnosis should be suspected in every patient with a new or progressive radi ographic in \201 ltrate with purulent respiratory secretions plus new onset of fever, leuc ocytosis or hypoxaemia. Clinical approach Initial clinical approach should include: \200 COPD Respiratory failure Patient-related risk factors include: An important issue in HAP is the increasing rates of HAP episodes due to MDR pathogens, especially in ICU. Risk factors associated with MDR HAP are: \200 Antimicrobial therapy in last 90 days \200 Current hospitalization >5 days \200 Immunosuppressive disease or therapy \200 Hospitalization for >2 days in the preced ing 90 days \200 Residence in nursing home \200 \200\230Homecare \200\231 \200 Chron ic dyalisis \200 Family member with MDR infection Comprehensive medical history, looking for risk factors associated with speci \201 c patho gens. CXR, evaluating the presence of complications such as pleural effusion. Arterial oxyg enation/respiratory rate assessment Assess presence of organ dysfunction/evaluate severity scores. All patients should have blood cultures collected Samples of lower respiratory trac t secretions should be obtained (see below). Microbiological \201 agnosis Quantitative cu ltures should be obtained by non-invasive (endotracheal aspirate) or invasive techniques (b ronchos- copy-guided bronchoalveolar lavage or protected speci- men brush (PSB)). The choic e of method depends on local expertise, availability and cost. A large RCT failed in dem- \200 \200 Etiology Most common pathogens include aerobic Gram-negative bacilli (P. aeruginosa, E. col i, K. pneumoniae and Acinetobacter baumannii). Gram-positive cocci, S. aureus, particularly MRSA, are a very important issue in most ICUs. Polymicrobial episodes are very common. 279 CHAPTER 17.16 Hospital-acquired pneumonia onstrating any difference between an invasive and non- invasive approach. To achieve optimal antibiotic treatment, appropriate dosage, route of administration and re gimen should be employed to ensure tissue penetration (e.g. linezolid has a better tissue p enetration than vancomycin when treating VAP due to MRSA). Modi \201 cation of empirical a ntimicrobial treatment (de-escalation, rescue therapy) The empiric antibiotic treatment mus t be reviewed once the culture results are available. De-escalation consists of a broad-spe ctrum initial antibiotic therapy, followed by a simpli \201 cation of the regimen based on culture results and clinical evolution. Such a strategy is associated with lower mortality . Rescue therapy is implemented when there is primary resistance on cultures or a poor clin ical evolution. Evolution assessment Clinical parameters such as fever and resolution of hy pox- aemia (PO2/FiO2 ratio) are valuable markers of clinical resolution in VAP. Use of clin ical scores, such as CPIS (Clinical Pulmonary Infection Score), may be useful. Use of bioma rkers such as CRP or procalcitonin are promising strategies to evaluate resolution, but the ir use still needs to be evaluated by further studies. Optimal duration of therapy is unkno wn. A randomized trial concluded that outcomes are similar when treating patients for 8 or 15 days. Treatment The therapeutic approach of HAP/VAP must be patient- based and institution-speci \201 c. Empirical treatment choice must be guided by characteristics of patients, local pa ttern of antimicrobial resistance and direct staining of respiratory samples. Initial empir ic therapy for HAP/VAP according to time to onset and presence of risk factors Onset Pathogens Antibiotic therapy S. pneumoniae H. in \202 unzae MSSA Enterobacteriaceae GNB MDR P. aeruginosa K. pneumoniae Acinetobacter baumannii Early onset without risk factors Ceftriaxone or Quinolone or Ampi/sulbactam or Ertapenem Antipseudomonal cephalosporin or An tipseudomonal carbapenem or Piperacilin/tazobactam and quinolone or aminoglycoside \200 Late onset or with risk factors for MDR pathogen Further reading American Thoracic Society. Guidelines for the management of adults with hos pital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Cri t Care Med 2005; 171: 388 \200\223416. MRSA Linezolid or vancomycin Canadian Critical Care Trial Group. A randomized trial of diagnostic techniques for ventila tor-associated pneumonia. N Engl J Med 2006; 355: 2619 \200\22330. Key points \200 Empirical antibiotic choice driven by local micro- biological data Data demonstrate an impo rtant variability in pathogens in different centers and different ICUs. Prompt initiation o f appropriate antimicrobial treatment Appropriate initial antibiotic treatment is associate d with better outcomes in HAP/VAP patients. The shorter the delay in starting empirical tre atment, the better the impact on prognosis, LOS and cost. Appropriateness of antimicrobial treatment (dose, pharmacokinetics/dynamics considerations, tissue penetration) Chastre J, Wolff M, Fagon JY, et al. Comparison of 8 vs 15 days of antibiotic therapy for v entilator-associated pneumonia in adults: a randomized trial. JAMA 2003; 290: 2588-98. Rello J, S -Borges M, Correa H, et al. Variations in etiology of ventilator-associated pne umonia across four treatment sites: implications for antimicrobial prescribing practices. A m J Respir Crit Care Med 1999; 160: 608 \200\22313. Rello J, Vidaur L, Sandiumenge A, et al. De-escalation therapy in ventilator-associated pne umonia. Crit Care Med 2004; 32:2183 \200\22390. Resar R, Pronovost P, Haraden C, et al. Using a bundle approach to improve ventilator care processes and reduce ventilator- associated pneumonia. Jt Comm J Qual Patient Saf 2005; 31: 243 \200\2238. 280 B MADDEN Pulmonary hypertension De \201 nition Pulmonary hypertension is said to occur when the mean pulmonary artery pres sure exceeds 25mm Hg at rest or 30mm Hg with exercise. The term pulmonary arterial hyperten sion (PAH) denotes a series of apparently unre- lated disorders which share the histopathol ogical entity of plexogenic pulmonary arteriopathy (PPA). Examples include idiopathic PAH, familial PAH and pulmonary hyper- tension associated with scleroderma, hepatic cirrhosis, H IV infection and Eisenmenger \200\231s syndrome. In addition, pulmo- nary hypertension can occur in association with cardiac diseases (left heart failure, mitral valve disease), resp iratory disorders (emphysema, pulmonary \201 brosis), pulmonary thromboembolic disease an d various miscellaneous conditions. Although these latter conditions are more common causes of pulmonary hypertension, the severity of pulmonary hypertension is usually less than tha t seen in PAH and the histopathology is not PPA in nature. Idiopathic PAH was typically des cribed in young females, although with increasing awareness the condition is now being diag nosed in patients beyond the 4th and 5th decades of life. The incidence and prevalence of t he condi- tion is estimated to be 4 per million and 10 per million of the population, respe ctively. The prevalence of PAH is estimated to be in the region of 100 per million of the p opulation. The incidence and prevalence of pulmonary hypertension in patients with cardiac and respiratory disorders are not precisely known, although they are believed to be conside rably higher than for PAH. 5 Miscellaneous \200 Histiocytosis Lymphangioleiomyomatosis PAH is associated with a poor survival and a poor quality of life. There is no cure, limite d treatment options and incomplete understanding of the disease. Pathology PPA occurs in a select group of disorders. The reason why this pathological entit y occurs is not clear, although it is possible that the lung only has a \201 nite number of responses to injury which feed into \201 nal common pathway mecha- nisms. This may exp lain why similarities occur in patients with conditions such as obliterative bronchiolitis following lung transplantation and those with obliterative bronchiolitis associated with rh eumatoid disease or respiratory syncytial virus infection in childhood. Likewise, although many condi- tions have been implicated as causing ARDS, the pathology is similar regardless of etiology. In PPA there is initial vasocon- striction and subsequent smooth muscle migra tion from the inner half of the media of muscular pulmonary arterioles into the lumen to be come myo \201 broblasts capable of laying down either smooth muscle or \201 brous tissue . The cells pro- liferate in a concentric fashion and ultimately obliterate the lumen. When sectioned, the vessels have the appearance of a cut onion, hence the term onion skin proli feration. As the radius gets progressively compromised, the resistance to \202 ow increas es. At points of weakness in the vessel (proxi- mally at branching areas) the vessel disten ds and ruptures. Hemorrhage occurs and primitive blood vessels grow into this area in a hap hazard or plexiform arrangement. The combination of concentric laminar intimal (onion skin) pro- liferation and plexiform lesions is referred to as PPA. Some authors believe that ple xiform lesions may represent a form of collateral irculation. Why these particular changes occur in diseases with such diverse etiology and clinical presentation is not under- stood. Immunoreactive cells in the lung for gastrin-releasing peptide and calcitonin may be impor tant factors in smooth muscle migration. There is extensive ongoing research into endotheli al dysfunction in patients with PAH. Pulmonary h9ypertension Diagnostic classi \201 cation (World Congress on Pulmonary Hyperte nsion Venice 2003) 1 Pulmonary arterial hypertension (PAH) \200 \200 Idiopathic PAH Familial PAH Related to \200 \200 \200 \200 \200 Pulmonary capilla ry haemangiosis Pulmonary veno-occlusive disease Others (e.g. glycogen storage disease, spl enectomy) Connective tissue diseases HIV Portal hypertension Anorexigens Congenital heart diseases Survival PAH carries a poor prognosis, and for those patients with class IV New York Heart Association (NYHA) status, the 5-yr actuarial survival is signi \201 cantly lower than tha t for patients with lung, breast, prostate, colon and gastric carcinoma. A median survival of 2.8yrs has been reported for untreated patients in class III or IV NYHA. Survival and qu ality of life have improved for selected patients treated with agents such as endothelin re ceptor antago- nists, prostacyclin analogs and PDE inhibitors.