Further reading Delclaux C, L \200\231Her E, Alberti C, et al. Treatment of acute hypoxemic nonhypercapnic respiratory insuf \201 ciency with continuous posi- tive airway pressure d elivered by a face mask: a randomized con- trolled trial. JAMA 2000; 284: 2352 \200\22360. \200 \200 \200 \200 Giles TL, Lasserson TJ, Smith BJ, et al Continuous positive airways pressure for obstructiv e sleep apnoea in adults. Cochrane Database Syst Rev 2006; (1): CD001106. Application of CPAP in clinical settings Acute respiratory insuf \201 ciency \200\224as a bridge to recovery. Early clinico-physiological improvement, based upon sub- jective parame ters, respiratory rate and oxygenation improve, as compared with face mask oxygen alone. Ho wever, CPAP may not reduce intubation rates in acute lung injury. There remains some debate as to the minimum effective PEEP level to produce a CPAP effect on oxygena- tion that is n ot merely a high \202 ow phenomenon. This is particularly so with the availability of hig h= \202 ow humidi \201 ed oxygen systems through nasal cannulae. Placidi G, Cornacchia M, Polese G, et al. Chest physiotherapy with positive airway pressure : a pilot study of short-term effects on sputum clearance in patients with cystic \201 br osis and severe air- way obstruction. Respir Care 2006; 51: 1145 \200\22353. Richardson A, Killen A. How long do patients spend weaning from CPAP in critical care? Intens Crit Care Nurs 2006; 22: 206 \200\22313. Sullivan CE, Issa FG, Berthon-Jones M, et al. Reversal of obstructive sleep apnoea by conti nuous positive airway pressure applied through the nares. Lancet 1981;1: 862 \200\2235. 26 L MASCIA, M ZANIERATO, & M RANIERI Recruitment maneuvers If gas exchange and lung mechanics do not improve sub- stantially with recruitment maneuver s, the patients are considered to have a \200\230low potential for recruitment \200\231, a nd the use of higher level of PEEP may provide little bene \201 t and actually be harmful since application of PEEP may cause overdistention. Data suggest that patients with \200 \230high potential for recruit- ment \200\231 are those ventilated for not more than 48 \200\22372h, while patients with \200\230low potential for recruitment \200\231 are those ventilated for >3 days; the underlying disease responsible for ARDS (primary vs secondary A RDS) seems not to have a role in identifying responders or non-responders to recruitment ma neuvers. The mechanism underlying hypoxaemia in acute lung injury is intrapulmonary shunt due to non -ventilated but per- fused alveoli. Any maneuver that recruits lung volume and increases th e amount of aerated lung can be expected to improve gas exchange. However, the challenge is to recruit atelectatic alveoli without overdistending normal lung units. Although PEEP is the most commonly used method to achieve or maintain recruitment, others techniques have be en evaluated: volume recruitment maneuvers, prone position and HFOV. Volume recruitment man euvers, peri- odic in \202 ations to airways pressures of 35 \200\22345cm H2O sus- tained for 5 \200\22330s, are used to reverse alveolar derecruitment and to improve gas exchange w hile allowing acceptable ventilator pressure. In ALI/ARDS, inadequate levels of PEEP may ca use tidal recruitment/derecruitment of part of the consolidated lung and may expose these r egions to shear stress. The combined use of low tidal volume and PEEP may minimize VILI. Re cruitment maneuvers are procedures speci \201 cally designed to reach an opening pressure suf \201 cient to open the collapsed lung regions that, in association with an increased l evel of PEEP post- recruitment maneuver, may improve gas exchange, reducing intrapulmonary shunt. However, the effectiveness of recruiting maneuvers to improve oxygenation is also in \202 uenced by elastic proper- ties of the chest wall since part of the pressure applied to the respiratory system during the recruiting maneuvers can be dissipated against a stiff chest wall. Moreover, the response to recruitment maneuvers is a function of the potential for recruitment (unstable units), the phase and extent of lung injury, the level of PEEP a nd the characteris- tics of the recruiting technique. In clinical practice, RM may play a r ole in the lung-protective ventilatory strategies based on the so-called \200\230open lung approach \200\231; however, their utility has not been con \201 rmed by large clinical tr ials. Lung recruitment maneuvers have also been successfully used in patients during genera l anesthesia, to restore the decreased respiratory system compliance and oxygenation. Monitoring Clinical evaluation of the response to recruitment manoeu- vres and of its poten tial use can be evaluated at the bedside. More accurate evaluation of the percentage of pot entially recruitable lung may be obtained by analysis of CT images or of respiratory mechan ics. Clinical evaluation After performing a recruitment maneuver, its ef \201 cacy can be evalu ated at the bedside by looking at the values of plateau pressure (or tidal volume if the pa tient is ventilated in a pressure-controlled mode), PaO2 and PaCO2. If the recruitment mane uver: (1) decreases plateau pressure (or increases tidal volume if the patient is ventilate d in a pressure-controlled mode); (2) increases PaO2; and (3) decreases PaCO2 (even if only few mm Hg), the patients may be considered as a responder. CT scanning Analysis of CT \201 ndings can identify the distribution of normally aerated lung regions in the non-dependent regions, and poorly aerated lung regions distributed in t he dependent lung region. The CT analysis can assess the effects of the recruitment maneuve rs as well as its safety, and most importantly the adequate PEEP levels to keep the lungs o pened after the recruitment maneuvers. With an inspiratory and expiratory pause image acqui sition of the lung, the regional tidal volume distribution can be assessed. Techniques Several approaches have been used to perform the recruit- ment maneuvers: \200 Respiratory mechanics Pressure \200\223volume (P/V) curve Analysis of P/V curves can con \201 rm that the lower in \202 ec- tion point and upper in \202 ection point correspond t o CT scan evidence of atelectasis and overdistension. Alveolar recruitment is con \201 rme d to occur continuously and along the inspiratory limb of the P/V curve, while the critical point for lung derecruitment is identi \201 ed below the point of maximum curvature of th e de \202 ation limb. Sustained in \202 ation by application of CPAP at 30 \200\22340cm H2O for 40s. Incremental PEEP on maximum pressure: PEEP is increased in increments of 5cm H2O from a baseline PEEP to 35cm H2O, reducing tidal volume to limit peak inspiratory pressure to 35cm H2O. CPAP of 35cm H2O is maintained for 30s. Intermittent higher tidal volume in pressure-controlled ven tilation applied with escalating PEEP and constant driving pressure: peak pressure of 45cm H2O, I:E ratio of 1:2 and PEEP level of 16cm H2O for 2min. Stress index The analysis of the dynamic pressure/time (P/T) curve during constant \202 o w ventilation (stress index) is a new parameter to identify clinically the best compromise between alveolar recruitment and overdistention. The stress index is the exponent of the eq uation correlating the airway pressure pro \201 le and time during each tidal volume. A st ress index <1 is associated with recruitment, assessed by CT scan, whereas a stress index > 1 is associ- ated with hyperin \202 ation. Modern ventilators are able to If gas exchange and lung mechanics improve substantially with recruitment maneuvers, the pa tients should be con- sidered to have \200\230high potential for recruitment \200\231. How ever, in gauging response to PEEP, it is important to consider the oxygenation response as well as CO2 exchange: when PEEP is applied, PaO2 tends to increase and CO2 exchange may imp rove, re \202 ecting increased alveolar ventilation. 27 CHAPTER 1.11 Recruitment maneuvers Further reading Gattinoni L, Caironi P, Cressoni M, et al. Lung recruitment in patients wit h the acute respiratory distress syndrome. N Engl J Med 2006; 354: 1775 \200\22386. deliver square-wave inspiratory flow profiles and are equipped with monitoring that provide s on-line dynamic P/T curves. Risks The potential risks of the recruitment maneuvers are barotrauma (high transpulmonary pressure) and haemody- namic derangement (high pleural pressure). In patients with \200 \230low potential for recruitment \200\231 (non-responders), application of recruiting mane uvers may result in a sub- stantial haemodynamic impairment. These effects are due a reduce d preload secondary to transmission of pleural pressure to intrathoracic structures and an increased after- load due to increased lung volume. The degree of pleural pressure transmit ted is higher in patients with a stiff chest wall than in patients with a normal chest wall . Therefore, the use of recruitment maneuvers may be indicated only in patients with high p otential for recruitment, keeping in mind that after the maneuver, the level of PEEP has to be increased otherwise its bene \201 cial effects on gas exchange and respiratory mechani cs will be lost in a few minutes. Grasso S, Mascia L, Del Turco M, et al. Effects of recruiting maneu- vers in patients with acute respiratory distress syndrome ventilated with protective ventilatory strategy. Anesth esiology 2002; 96: 795 \200\223802. Grasso S, Terragni P, Mascia L, et al. Airway pressure \200\223time curve pro \201 le (str ess index) detects tidal recruitment/hyperin \202 ation in experimental acute lung injury. Crit Care Med 2004; 32: 1018 \200\22327. Lachmann B. Open up the lung and keep the lung op en. Intensive Care Med 1992; 18: 319 \200\22321. Lim S-C, Adams AB, Simson DA, et al. Intercoparison of recruit- ment maneuvers ef \201 cac y in three models of acute injury. Crit Care Med 2004: 32: 2371 \200\2237. 28 M SHANKAR HARI & A JONES Prone position ventilation Other effects \200 \200 Acute lung injury (ALI) occurs in 7.1% of ICU admissions, with 55% of these patients progre ssing to ARDS within 72h. The population-based incidence of ALI is estimated to be 78.9 per 100 000 person-years. Interestingly, respiratory failure is thought to be the primary caus e of death in only 16% of patients with ARDS. However, it is now recognized that mechanical ventilation may itself be directly harmful to the injured lung, so-called ventilator induc ed lung injury (VILI), and contribute to the development of multi-organ dysfunction. As suc h, the present literature supports a lung-protective approach to ventilation in patients wi th ARDS, via limitations on plateau pressure and tidal volume. Prone position ventilation i s one of several adjuncts employed by clinicians when adequate gas exchange can- not be ach ieved with conventional ventilatory strategies, and has been used effectively to improve ox ygenation in patients with both ALI and ARDS from a wide range of aetiologies. Reduction in VILI Reduction in extravascular lung water (EVLW) Effect on alveolar ventilation Prone positioning results in a more homogenous distribution of alveolar pressure and ventilation, due a reduction in thoraco-abdominal compliance secon dary to restriction of the anterior thoracic and abdominal walls. The more uniform distribu tion of alveolar pressure also prevents collapse of vulnerable lung units on expiration, ma intaining alveolar recruitment. In addition, in the prone position, the heart is dependent and the diaphragm is caudally displaced, reducing posterior compression of the lung parench yma and improving regional ventilation in these areas. The net result of these effects is a reduction in intrapulmonary shunt and an improvement in hypoxaemia. There is emerg- ing ev idence that relative to the semi-recumbent position, indices of lung stress are reduced in the prone position, offering the potential for prone positioning to attenuate VILI. Oxygenation response to prone position In numerous observational and randomized studies in ALI/ ARDS, prone positioning results in improved oxygenation (increased PaO2/FiO2 of 10 \200\22330%) in 70 \200\22380% of patients. Three oxygenation response patterns have been described. \200 Effects on pulmonary perfusion Traditionally, the effect of gravity has been used to explai n the heterogeneity in regional pulmonary perfusion. As such, in ALI, perfusion and atelect asis are both greater in the dependent lung, resulting in shunt and hypoxaemia. It was sugg ested that prone positioning would allow redis- tribution of perfusion to aerated lung regi ons and thus improve shunt and oxygenation. Experimental studies have had con \202 icting results, and the effect of the prone position on perfusion distribution, independent of cha nges in ventilation, are thought to be minimal. Prolonged prone position (18h) may also red uce EVLW . Non-responders (20%) \200\224no improvement in oxygena- tion Responders (80%) \200 Persistent: improve oxygenation and maintain improved oxygenation on turning supine (50%) N on-persistent: improvement in oxygenation is not sustained on returning to supine position (30%) Attempts have been to de \201 ne factors that predict a favor- able response to oxyg enation. Although in an individual subject response to prone positioning may vary from one episode to another, the following have generally been asso- ciated with a more favorable ox ygenation response. \200 \200 \200 \200 \200 \200 Technique of prone position Prone positioning requires a concerted effort from all members of the multi-disciplinary team. Although there is no standard approach to the prone maneuve r, detailed descriptions of appropriate algorithms have been pub- lished. Specialist beds d o exist, but are not commonplace, with most units using a modi \201 ed two-step \200\230l ogroll \200\231, with speci \201 c individuals assigned to manage the ETT, vascular access devices and surgical drains. At least one of those present must be competent to undertake re-intubation if required. Prone positioning requires no additional monitor- ing, although ECG leads must be placed on the back. The need for endotracheal suctioning may increase in frequency and there needs to be strict attention to potential pressure areas, including reg ular repositioning of the patient, pad- ding to vulnerable areas and speci \201 c attentio n to ETT and catheter entry sites. As with the standard supine position, elevation of the h ead of the bed (reverse Trendelenberg) may reduce the risk of pharyngeal aspiration as well as help minimize ocular and facial oedema whilst prone. Despite this, however, enteral fee ding may be more problematic in the prone position, and a reduction in the target rate may need to be considered to minimize potential complica- tions. In the presence of adequate le vels of sedation, paralysis is not usually required, and may have detrimental effects on di aphragm-related benefits. The optimal duration of prone positioning is unknown. Whilst most earlier studies used repeated periods of up to 6 \200\2238h/day, more recent studies have preferred more prolonged Higher baseline PaCO2 Improved PaCO2 clearance during prone positioning More severe lung in jury Early vs late lung injury Extrapulmonary vs pulmonary lung injury Lobar radiological p attern of lung injury. Physiological effects of prone position The improvement in oxygenation and respiratory mech anics observed during prone positioning result from a synergistic interaction of the effect s of the prone position on the lung parenchyma, chest and abdominal wall, and the pulmonary circulation. The physiological effects of prone position Ventilation-related effects \200 More homogenous distribution of ventilation due to favorable changes in thoraco-abdominal c ompliance Improved alveolar recruitment Sustained effect of recruitment maneuvers Better dr ainage of secretions \200 \200 Perfusion-related effects \200 More homogenous distribution of perfusion 29 CHAPTER 1.12 Prone position ventilation \200 \200 Nerve compression Persistent hypoxaemia Haemodynamic instability periods (up to 20h day), in an attempt to make use of the persisting oxygenation bene \201 t via application of a lung- protective ventilatory approach. Although manually oner- ous, with appropriate equipment, guidelines and training in place, prone positioning is a relat ively simple and safe procedure with a low economic burden. Outcome with prone position ventilation There have been four randomized controlled trials o n prone positioning, and none has shown a survival advantage. However, one small study was con \201 ned to patients with polytrauma, and a second larger study considered patients wi th acute hypoxaemic respiratory failure of all causes, of whom only 45% had ALI/ARDS. In th e largest study in unselected patients with ALI/ARDS, 304 patients were randomized to recei ve supine vs prone ventilation (>6h) for 10 days. Although oxygenation improved during pron e positioning, there was no difference in 10-day, ICU and 6-month mortality, non-pulmonary organ failure or iatro- genic complications, between the two groups. A post hoc analysis im plied improved 10-day survival with prone venti- lation in the sickest patients (PaO2/FiO2 <88; Simpli \201 ed Acute Physiology Score II (SAPS II) >49), but this did not persist to ICU discharge. However, this study employed relatively short periods of prone ventilation a nd a ventila- tory strategy (Vt >10ml/kg and relatively low levels of PEEP) that preceded p resent lung-protective approaches. In a more recent study, 136 patients with early severe A RDS were randomized to supine or prolonged prone ventilation (20h/day), with an established protective venti- latory approach. Although there no difference in overall mortality, the 12 \200\22315% and 20 \200\22325% reduction in ICU and hospital mortality in the prone grou p is clinically intriguing, especially as they were deemed to be sicker at study entry. Contraindications Contraindications to prone positioning detailed in previous studies inclu de; \200 \200 \200 \200 \200 \200 \200 severe haemodynamic instability/arrythmias spinal instability pelvic fractures/multiple tra uma pregnancy raised ICP recent tracheal surgery or sternotomy abdominal surgey/raised intr a-abdominal pressure Spinal instability is the main absolute contraindication, although haemodynamic instability and arrythmias are strong relative contraindications due to the inherent dif \201 - culti es in immediate access for CPR (cardiopulmonary resuscitation) in the prone position. Prone positioning in patients with wounds/surgical intervention to the face or ventral body surf ace, or in obese individuals, may cause special problems, but can be possible on an individ ual patient basis. Complications Prone positioning is associated with complications which have both immediate and long term effects for the patient. Marked facial oedema is almost ubiquitous, and press ure sores to the face, anterior chest wall, and iliac crests are common unless speci \201 cally targeted. Displacement or mal- function of the ETT, chest drains and vascular access are potentially serious complications during the proning maneuver. Conclusions Prone positioning improves oxygenation but not outcome in unselected patients w ith ARDS. With appropriate education and training, it can be safely performed in most patie nts. At present it should be considered an adjunct for those patients with severe ARDS fail ing to progress or deteriorating with conventional ventilatory approaches. We advocate more prolonged periods of prone position, incorporating existing lung-protective approaches to mechanical ventilation. Complications observed with prone positioning During turning \200 \200 \200 \200 \200 \200 Loss of airway and vascular access Injury to cervical spine, shoulder Increased sedation re quirements Transient hypoxaemia Cardiac arrhythmia Haemodynamic instability Further reading Gattinoni L, Tognoni G, Pesenti A, et al. Effect of prone positioning on th e survival of patients with acute respiratory failure. N Eng J Med 2001; 345: 568 \200\2237 3. During prone position ventilation \200 Guerin C, Gaillard S, Lemasson S et al Effects of systematic prone positioning in hypoxemic acute respiratory failure: a randomized controlled trial. JAMA 2004; 292: 2379 \200\22387. Oedema and pressure sores of the face, thorax and iliac crests Conjuctival oedema and hemor rhage Retinal damage Airway obstruction Malfunction of vascular access, bladder catheter, e nteral feeding tubes, chest drains Intolerance to enteral feeding \200 \200 \200 Mancebo J, Fernandez R, Blanch L et al. A Multicenter Trial Of Prolonged Prone Ventilation In Severe Acute Respiratory Distress Syndrome. Am J Resp Crit Care Med 2006; 173: 1233 \200 \2239. Voggenreiter G, Aufmkolk M, Stiletto R et al. Prone positioning improves oxygenation in pos t-traumatic lung injury \200\224a prospective randomized trial. J Trauma 2005; 59: 333 \200 \22341. 30 S SINGH Non-invasive positive pressure ventilation (NIPPV) Introduction Non-invasive positive pressure ventilation (NIPPV) is the delivery of mechanic ally assisted or generated breaths through a facial interface, without the placement of an arti- \201 cial airway, such as an ETT or a tracheostomy. It is an estab- lished alternat ive to invasive mechanical ventilation, for selected patients with ARF, and as a weaning mo de following extubation or tracheostomy decannulation. However, it does not replace invasiv e mechanical ventilation in patients requiring emergent endotracheal intubation. instability) are less common in NIPPV. Local skin damage is related to pressure effects of the mask and straps. Cushioning the forehead and the bridge of the nose helps. Mask leaks a re common and do not preclude NIPPV. Consider using different masks or ventilator settings. Eye irritation and sinus congestion may occur and may neces- sitate lower inspiratory pres sures or the use of a facial mask rather than a nasal mask. Gastric distension occurs with some frequency but is rarely signi \201 cant. Routine use of a nasogastric tube is not war ranted. Barotrauma is uncommon in NIPPV when administered in the pressure support or bileve l modes. Adverse haemodynamic effects due to NIPPV are unusual. Bene \201 ts NIPPV is a safe, effective technique that can avoid the side effects associat ed with endotracheal intubation. It is prima- rily used to avert invasive mechanical ventil ation in patients with early acute respiratory failure, and prevent re-intubation in patien ts with recurrent weaning failure. NIPPV preserves upper airway defense mechanisms, speech and swallowing. NIPPV improves alveolar ventilation, decreases work of breathing and reduce s intubation rates, length of hospital stay morbidity (i.e. pneumonia) and mortality. These are greatest for patients with acute exacerbations of COPD associated with hypercapnic res piratory failure. There is also bene \201 t in cardiogenic pulmonary oedema complicated by hypercapnia. Conversely, failure of NIPPV to prevent intubation has been associated with a higher mortality in patients with respiratory failure due to other causes, emphasizing the need for careful patient selection and monitoring for markers of early of treatment failur e. Indications The success of NIPPV depends on several factors, such as type of ARF, the under lying disease, location of treatment, experience of the team. The timing of initiation and dura- tion of use are also important for outcomes. Guidelines for the use of NIPPV improve the utilization and process of care, without changing clinical outcomes Acute hypercapnic respiratory failure Patients with acute hypercapnic respiratory acidosis secondary to an exacerbation of COPD bene \201 t the most from NIPPV, and are the best stu died group in the context of randomized controlled trials, and systematic reviews of NIPPV for ARF. Medical treatment failure rates vary between 27 and 74% from studies. The successf ul use of NIPPV can reduce mortality (relative risk (RR) 0.41), intu- bation rates (RR 0.42 ) and treatment failure rates (RR 0.51). It can also reduce length of hospital stay, and ma y be cost- effective through reduced ICU admissions/tracheostomy rates. These bene \201 ts are for patients with mild to moder- ate ARF (i.e. pH <7.3 and >7.25), who can be managed on a dedicated general ward/intermediate care setting with trained staff. The bene \201 ts are less and potentially harmful (i.e. through delayed intubation) in the more severely il l patients, who should be managed in a higher dependency setting, with greater staf \201 n g and monitoring, thus allowing intubation without delay if deemed necessary. There is no e vidence to suggest that NIPPV can prevent acute respira- tory distress/failure in mild exac erbations (i.e. pH >7.35, respiratory rate RR <20). There are no robust, easily reproducibl e clinical predictors of success/failure in acute exacerbations of COPD. Poor signs include an increase in respiratory rate and/or worse pH at 1 \200\2232h post-initiation. A Glasgow Coma Score below 11, and/or an APACHE II index of >29 can predict increasing need for intu bation. Contraindications Other than the need for emergent intubation, contraindi- cations for NIPP V include cardiorespiratory arrest, non- respiratory system organ failure (e.g. severe ence phalopathy, haemodynamic instability, severe gastrointestinal bleeding), facial or upper ai rway trauma, post-neurosurgery to the head, loss of airway patency, excessive airway secret ions or lack of cooperation with a high aspiration risk. Severe respiratory acidosis is not a contraindication to NIPPV, so long as intubation is available in an ICU setting if the N IPPV trial fails. In a case \200\223control study of 64 patients with COPD and severe hyper capnic respiratory failure (mean pH 7.18) who received NIPPV, 38% never required an ETT. Th ose who failed NIPPV and required intubation were not harmed by the delayed intubation and prolonged acidaemia. Technical considerations Pressure-cycled modes (pressure support or bilevel, BiPAP) are pre ferred for patient comfort, although volume- cycled modes may further reduce the work of br eathing. Delivery through standard ventilators can offer time-cycled options to improve syn chrony, precise O2 concentrations and enhanced CO2 clearance. Full face masks, nasal masks or alternatives such as helmets are available. Initiation requires dedicated staff, awarene ss of mask-related complications and troubleshooting skills. Early clinico- physiological a ssessment of success/failure by blood gasses and respiratory rate at 1h is vital. Hypoxaemic respiratory failure The ef \201 cacy of NIPPV in patients with hypoxaemic respi ra- tory failure has been demonstrated in pneumonia, immunosuppression, and following singl e lung resection. However, the studies have generally enrolled patients with moderate ARF, in whom emergent endotracheal intubation was not necessary. In a heterogeneous population o f 105 ICU patients, bilevel NIPPV decreased the need for intubation (25 vs 52%) and the inc idence of septic shock (12 vs 31%), improved ICU mortality (18 vs 39%) and increased 90-day survival vs high concentration oxygen. The bene \201 ts of NIPPV in ARF (PaO2/FiO2 <33kPa ) due to Complications Complications associated with invasive ventilation (e.g. nosocomial pneumonia , barotrauma, haemodynamic 31 CHAPTER 1.13 Non-invasive positive pressure ventilation (NIPPV) pneumonia may be limited, to those with underlying COPD, although a trial in all comers is justi \201 ed. Asthma Only one prospective trial has adequately assessed the value of NIPPV in acute asthm a (not requiring emergent intubation). Using sham (subtherapeutic BiPAP) as the con- trol a rm, NIPPV improved lung function and reduced admission rates from the emergency room. Alternative to invasive ventilation Weaning off invasive ventilation Patients with COPD rec eiving invasive mechanical ventilation for >48h and failing SBTs can be safely extubated to NIPPV, shortening ICU stay and reducing mortality. ARDS There is insuf \201 cient information to recommend the use of NIPPV in this setting. If used, then an ICU setting with early recognition of failure and intubation is advisable. Extubation failure NIPPV reduces re-intubation rates when used early in patients at risk of post-extubation failure (i.e. previous extubation failure, high APACHE score >12, hypercap nia, chronic heart failure, poor cough, stridor, co-morbidities). However, it is ineffectiv e, and potentially harmful in post- extubation respiratory failure 48h on, due to delayed r e- intubation. Thus the early use of NIPPV is once again emphasized for best ef \201 cacy. It has been used successfully to pre-oxygenate patients prior to endotracheal intuba- tion , compared with bag-valve-mask ventilation. Neuromuscular disease NIPPV has been used successfully to support decompen- sated neuromusc ular diseases such Guillan \200\223Barre syn- drome and muscular dystrophies to recovery, w hile it is also a bridge to transplantation in cystic \201 brosis, avoiding intubation. Further reading Demoule A, Girou E, Richard JC, et al. Bene \201 ts and risks of success o r failure of noninvasive ventilation. Intensive Care Med 2006; 32: 1756. Other speci \201 c indications Cardiogenic pulmonary oedema. NIPPV reduces the incidence o f intubation compared with standard medical therapy and oxygen alone. It is equivalent to C PAP, but may be more advantageous in patients with associated hypercapnia. There appears to be no additional risk of acute myocardial infarction associated with the use of NIPPV in t his setting. Evans TW. International Consensus Conferences in Intensive Care Medicine: non-invasive posi tive pressure ventilation in acute respiratory failure. Intensive Care Med 2000; 27: 166 \200\22378. Liesching T, Kwok H, Hill NS. Acute applications of noninvasive positive pressure ventilation. Chest 2003; 124: 699. Lightowler J, Wedzicha J, Elliott M, et al. Non-invasive positive pressure ventilation to t reat respiratory failure resulting from exacerbations of chronic obstructive pulmonary dise ase. BMJ 2003; 326: 185. Patients with \200\230do not intubate \200\231 orders. In patients unsuitable for, or decl ining intubation for ARF, NIPPV can act as a bridge to recovery in >40%. It may also be use d as palliation for breathlessness if tolerated. Sinuff, T, Cook, DJ, Randall, J, et al. Evaluation of a practice guideline for noninvasive positive-pressure ventilation for acute respiratory failure. Chest 2003; 123: 2062. 32 B CHARLES & G PEEK Extracorporeal membrane oxygenation (ECMO) for adults in respiratory failure Introduction Extracorporeal membrane oxygenation (ECMO) uses modi \201 ed cardiopulmonary bypass technology to provide prolonged respiratory or cardiorespiratory support to patients of all ages who have failed conventional intensive care. Venous blood is drained into the ECMO circuit where it is oxygenated, carbon dioxide is removed and it is rewarmed before be ing returned to the body. ECMO can be used to support any patient with severe but potential ly reversible respiratory, cardiac or multi-organ failure who does not have a contraindicat ion to limited heparinization. Heat exchanger There is considerable heat loss from the circuit. Normo- thermia is maintain ed with a heat exchanger which is usually integral to the oxygenator. Pressure transducers Pressure transducers constantly measure pre- and post- oxygenator pres sures. A high post-oxygenator pressure signi \201 es a cannula obstruction, and an increas ing pressure drop across the oxygenator implies membrane lung failure. Cannulation Cannulation for VV is percutaneous. The patient must be anesthetized and paraly zed to reduce the risk of air embolism. Types of ECMO There are two types: venoarterial ECMO (VA ECMO) and venovenous ECMO (VV ECMO ). VA ECMO drains deoxygenated blood from a central vein or right atrium and returns it to a central artery. This \202 ow is in addition to the native cardiac output, hence there i s partial cardiac support. VV ECMO drains blood from a central vein or right atrium and ret urns the oxygenated blood back to a large vein. The volumes of blood drained from and re-in fused into the venous system are equal, therefore there is no change in CVP or ventricular \201 lling; the pulmonary artery pressure usually falls due to the increased venous oxyge n tension. Native cardiac output provides the full systemic blood \202 ow, which usually improves with the reduction in airway pressure. VV ECMO is preferred to VA ECMO in the trea tment of respiratory failure as normal pulmonary blood \202 ow is maintained. ECMO patient management Maintain haemostasis The principle is to balance the anticoagulatio n so as to pre- vent signi \201 cant circuit thrombus formation without causing major hemo rrhage. The main agent used is heparin. Anticoagulation is initiated with a bolus of 75 uni ts/kg of heparin IV followed by an infusion to achieve an activated clotting time of 180 \200\223200s. The international normalized ratio (INR), \201 brinogen levels and platelet count should also be monitored and corrected. Progressive elevation of D-dimers can indica te thrombolytic activity related to the circuit or patient. Allow lung recovery by use of gentle ventilation. Once on ECMO, the high pre-ECMO ventilato r settings are gradually decreased to \200\230rest settings \200\231 which is positive ins piratory presure (PIP) 20 \200\22325, PEEP 10 \200\22315cm H2O, FiO2 0.3, and rate 10/min. The aim is to reduce ventilator- induced barotrauma and oxygen toxicity. The ECMO circuit The ECMO circuit consists of cannulae, pump, membrane lung, servo-regulato r, heat exchanger, pressure transducers and a bridge. It is designed to eliminate areas of stasis so that only small amounts of anticoagulation are required. Provide adequate systemic oxygen delivery Oxygen delivery is dependent on : \200 \200 \200 \200 \200 Capacity (rated \202 ow) of membrane oxygenator Oxygen binding capacity of blood Flow thr ough circuit Oxygen uptake through native lung Cardiac output Oxygenator The key component of the circuit is the oxygenator or membrane lung. Modern circ uits use non-porous hollow \201 bre oxygenators (polymethylpentene). They have much bette r gas exchange, lower priming volume and resistance, and are more biocompatible than previo us silicone devices. Oxygen content of blood = (1.39 x Hb x % saturations) + dissolved Hb (minimal and usually i gnored) Cannulae The amount of oxygen delivered by the ECMO circuit is related to the oxygen conten t of the blood and the ECMO circuit \202 ow. This is limited by the size and number of ve nous drainage cannulae. The shortest widest cannula possible should be used. On ECMO, to maximize oxygen delivery, the oxygen content of blood needs to be optimized by maintaining a normal Hb concentration of 12 \200\22314g/dl. Within the range of the rated \202 ow (design maximum for the oxygenator), increasing the \202 ow can increase oxygena tion. Oxygenation is assessed during VV ECMO using the arterial PaO2 and SpO2. Carbon dioxi de removal Carbon dioxide clearance is more ef \201 cient than oxygen uptake because unlik e oxygen it is diffusion dependent. As the sweep gas contains no carbon dioxide, the diffus ion gradient is highest at the inlet end of the oxygenator. Increasing the sweep gas \202 ow will clear more carbon dioxide. Pump The pump pulls bloods either from a small compliance chamber (bladder) or directly fro m the patient, pumps it through the oxygenator and then back to the patient. It is vital to have a mechanism preventing negative pressure developing proximally when the venous \202 ow is inadequate as this pressure, if unchecked, can cause damage to the atrium and vessel wall as it is \200\230sucked in \200\231. It can also cause haemolysis and cavitation as gas is pulled out of solution. 33 CHAPTER 1.14 ECMO for adults in respiratory failure conditions such as pulmonary \201 brosis are excluded as they are unlikely to recover wit h ECMO support. Though carbon dioxide removal is relatively independent of blood \202 ow rate it is depen dent on the surface area of the gas-exchanging membrane. When the effective gas exchange ar ea decreases, CO2 clearance is affected before oxygenation is. Evidence The CESAR (Conventional Ventilation or ECMO for Severe Adult Respiratory failure) trial is a multi-center RCT conducted in the UK It evaluates survival without severe disabi lity at 6 months and the cost \200\223bene \201 ts of ECMO vs conventional ventila- tion. A total of 180 patients were recruited and the result is currently awaited. The only other trial dates back to the 1970s. This was a multi-center trial sponsored by the National Inst itutes of Health and it compared VA ECMO with conventional ventilation in adults. This tria l did not show any difference in outcome, but case selection, ECMO techniques and technolog y, and ventilation strategies in this trial have been superseded by modern protocols. ECMO is an evidence-based therapy for neonates with severe respiratory failure. The ELSO registr y (1990 \200\2232006) shows a 59% survival for adult ECMO patients with respiratory failure , and our experience in Glen \201 eld (Leicester UK) is similar, with a survival of 66%. Intensive care Normal intensive care principles apply to ECMO patients. Full nutrition and appropriate use of antibiotics, steroids and other drugs are essential. In addition to an I ntensive Care Nurse, there is an ECMO specialist with the patient and circuit at all times. The ECMO specialist is trained in the management of ECMO circuit and any potential com- pl ications. Weaning, \200\230trial off \200\231 and decannulation The ECMO \202 ow rate is reduced as the patient gets better. This is shown by improved gas exchange, lung compliance and rad iological appearance. Once the \202 ow has come down to 1l/min the patient is usually rea dy to come off ECMO. To trial off VV ECMO, the patient is ventilated using optimum settings and the oxygen supply to the membrane oxygenator is disconnected. If the patient is stable for 2h, the cannulae can be removed. Conclusion ECMO is a rational treatment for adult respiratory failure in patients who have failed conventional treatment. The CESAR trial will further de \201 ne the role of ECMO in these patients. Complications The main complication of ECMO is bleeding. The main potential areas for bleed ing are gastrointestinal, intracra- nial and pulmonary, as well as cannulation sites. Bleed ing should be anticipated and actively prevented. Experienced medical staff should be invol ved in all procedures. Other complications are associated with cannulation, which includes pneumothorax, haemothorax, pericardial tamponade, vascular tears, embolization and complica tions associated with the circuit, including cannula obstruction, clots or air in the circu it, oxygenator failure and tubing rupture. Further reading ELSO. Extracorporeal cardiopulmonary support in critical care, 3rd edn. Ext racorporeal Life Support Organization, Ann Arbor, MI, 2005. Kolla S, Awad SS, Rich PB, et al. Extracorporeal life support for 100 adult patients with s evere respiratory failure. Ann Surg 1997; 226: 544 \200\22366.