Mechanical Ventilation of the Patient with Severe Chronic Obstructive

Intensive Care Med (1998) 24:898-910 © Springer-Verlag 1998

M. T. Gladwin Mechanical ventilation D. J. Pierson of the patient with severe chronic obstructive pulmonary disease

with severe COPD who requires mechanical ventila- Received: 1 January 1998 Accepted: 20 May 1998 tion.

M. T. Gladwin Department of Critical Care Medicine, NIH, Building 10, Non-invasive ventilation Room 7D43, 10 Center Drive, Bethesda, MD 20892, USA While this review focuses on mechanical ventilation of D. J. Pierson (~) the patient with COPD requiring endotracheal intuba- Division of Pulmonary and Critical Care Medicine, tion, it should be stressed that the primary goal is to Harborview Medical Center, 325 Ninth Avenue, avoid intubation whenever possible. There are two prin- Box 359762, Seattle, WA 98104, USA Tel.: 206-731-3356 cipal reasons for this. First, in most exacerbations of Fax: 2 06-7 31-85 84 COPD intubation is unnecessary if appropriate man- email: [email protected] agement is undertaken; and, secondly, intubation is fraught with iatrogenic, infectious and ventilator associated complications [1, 2]. It is clear that the intubated COPD patient has a high mortality rate, which probably Introduction reflects not only the severity of illness leading to intuba- Patients with severe chronic obstructive pulmonary dis- tion but also the incidence of complications inherent in ease (COPD) may require mechanical ventilation fol- the intubated and mechanically ventilated state [3, 4]. lowing cardiac or general surgery, in connection with Consequently, there is a growing body of literature that thoracic surgery such as lobectomy, wedge resection, supports the use of non-invasive positive- or negative- lung reduction or bullectomy, during an episode of acute pressure ventilation, in lieu of intubation, in COPD pa- respiratory failure (ARF) secondary to a disease other tients with acute ventilatory failure. than COPD such as sepsis, drug overdose, or trauma, In negative-pressure ventilation the thorax is en- or for acute-on-chronic respiratory failure (the COPD closed in an airtight system, often forming a seal around exacerbation) where acute illness, usually presumed to the neck, and application of negative (subatmospheric) be infectious in nature, destabilizes the characteristical- pressure around the chest during inspiration facilitates ly compensated state. chest wall expansion. There are various devices avail- Because of space limitations, this review will only able, ranging from the traditional iron lung and never briefly cover non-invasive ventilation and focus primar- lightweight fiberglass or plexiglass boxes that accommo- ily on the management of the intubated, mechanically date the entire body, to chest cuirasses and less rigid ventilated patient with COPD, with particular empha- body suits, tents and ponchos. Negative-pressure venti- sis on factors unique to this patient population such as lation has been successfully used in patients with chron- acid-base status, the propensity for dynamic hyperinfla- ic respiratory failure due to neuromuscular disease and tion and auto-PEEP, barotrauma, difficult weaning and patients with central hypoventilation [5-7], but a recent the prognosis following mechanical ventilation. It at- study failed to demonstrate a benefit in patients with se- tempts to identify important principles, and the ventila- vere COPD treated for 12 weeks [8]. Corrado et al. [9] tor manipulations required to execute them, that will retrospectively reviewed their experience treating pa- maximize the successful management of the patient tients with severe ventilatory failure, hypoxemia and 899 coma (Glasgow coma scale score 3-8) with negative- chard et al. [3] randomized 85 patients with severe pressure ventilation in an iron lung, and reported a COPD and acute ventilatory failure to non-invasive in- 70 % rate of recovery without intubation, although the spiratory positive airway pressure of 20 cm H20 or to lack of controls and retrospective nature of the study standard therapy. The intubation rates in the two groups leave many questions. Futhermore, some rigid nega- were 26 % and 74 %, respectively, with mortality 9 % tive-pressure devices, such as the chest cuirass, often do versus 29 %, complications 16 % versus 45 % and hospi- not fit well enough to form a tight seal, and the other de- tal length of stay 23 _+ 17 days versus 35 + 33 days. Kra- vices are tight fitting around the neck and can be confin- met et al. [17] studied 31 patients with acute ventilatory ing, precipitating anxiety in some patients [10]. failure and the rate of intubation was 9 % using non-in- Non-invasive positive-pressure ventilation (NPPV) vasive bilevel positive airway pressure in the subgroup is increasingly being employed in the treatment of the with COPD, as compared to 67 % for the standard treat- patient with COPD. It is primarily used to treat acute- ment group. on-chronic ventilatory failure but also appears to be ef- With the advent of NPPV, mandatory criteria for en- fective in weaning, as a bridge from the ventilator to dotracheal intubation are difficult to identify. While ap- spontaneous breathing [11-13]. Non-invasive positive- nea or agonal respiration, uncontrolled agitation, life- pressure ventilation can be delivered by volume- or threatening hypoxia, hemodynamic instability or se- pressure-limited ventilators or small portable devices, rious dysrhythmia and high risk for aspiration remain via face mask, nasal mask or nasal pillows. Portable de- relative exclusion criteria for NPPV and indications for vices effectively deliver bilevel positive airway pressure endotracheal intubation [16, 25], a falling arterial pH as well as continuous positive airway pressure (CPAP). secondary to ventilatory failure and rising PaCO 2 is less Alternatively, nasal or face masks can be applied using so. Thus, while a pH of 7.25 or less has been considered intensive care ventilators in the pressure-controlled or historically to represent a reasonable "line in the sand" pressure-support modes. The advantage of using stan- [26] beyond which intubation was required, this may dard ventilators over portable devices is that ventilator now be a manageable degree of ventilatory failure with alarms can be set, flow-by systems allow the patient to properly applied NPPV. Indeed, in a recent study [3], breathe without having to open valves, and there is less the average pH in patients successfully avoiding intuba- rebreathing of exhaled gas, a problem encountered tion was as low as 7.28 +/- 0.1 with average PaCO2 70 with some portable pressure-targeted devices when the +/-12 mmHg. The level of consciousness acceptable exhaled pressure setting is too low [14-16]. for non-invasive ventilation is likewise controversial. In either case, inspiratory and expiratory pressures While patients with severe obtundation have frequently are typically set initially at low levels for patient comfort been excluded from studies of NPPV, other authors and compliance and gradually raised to 8-20 cm H20 in- have documented success even in this group [9]. spiratory pressure and 0-6 cm H20 expiratory pressure. For more in-depth discussion of this rapidly evolving Two recent studies of NPPV in patients with severe ex- topic, the reader is referred to recent reviews on NPPV acerbations of COPD used different levels of pressure [27, 28] and negative-pressure ventilation [10, 29] in support with equally positive results. Kramer et al. [17] acute respiratory failure. used an average inspiratory pressure of 11 cm H20 delivered by nasal mask with an average expiratory pressure of 3 cm H20, while Brochard et al. [3] used an in- Acid-base issues spiratory pressure of 20 cm and expiratory pressure of 0 cm H20 delivered via face mask. Gastric distention In the face of increased dead space ventilation (VD/VT) with air is said to be less likely with pressure support and increased work of breathing, patients with severe levels less than 25 cm H20 [18]. As will be discussed la- COPD fiequently develop stable, compensated respira- ter, the application of modest amounts of expiratory po- tory acidosis. Arterial PCO 2 rises to allow adequate sitive airway pressure will reduce the inspiratory work steady-state elimination of CO2, at a reduced level of al- of breathing associated with dynamic hyperinflation. veolar ventilation (VA). The kidneys retain HCO3- until This is supported by the results of a trial using non-inva- a compensated state is achieved, characterized by a high sive CPAP without additional inspiratory pressure in pa- PaCO2, high HCO3- , and normal or near-normal arte- tients with COPD and acute ventilatory failure that rial pH. If the existence of this pre-existing state is not demonstrated improvements in dyspnea, inspiratory ef- appreciated by the clinician when such patients are first fort and arterial blood gas values [19]. intubated and ventilated, acute overventilation and po- Numerous uncontrolled studies as well as those using tentially life-threatening alkalemia can result (see Ta- historical controls have consistently demonstrated an ble 1) [25, 30]. Furthermore, if a "normal" minute venti- improvement in ventilatory failure with NPPV [18, lation (e. g. to PaCO2 40 mmHg) is pursued over the 20-23]. Three prospective randomized trials have next 2-3 days, the patient's kidneys will excrete the pre- demonstrated similar positive results [3, 17, 24]. Bro- viously retained HCO 3- until the overall acid-base bal- 900

Table 1 Acute alkalosis on initiating mechanicalventilation in the patient with acute-on-chronicventilatory failure: mechanismand effect on subsequent weaning Baseline Acute Initial values New stable state Return of acute compensated state decompensation on mechanical after 2-3 days at decompensation ventilation same settings during weaning Arterial blood values: pH (units) 7.38 7.24 7.56 7.40 7.24 PCO2 (mmHg) 56 86 40 40 56 HCO 3- (mEq/1) 33 36 34 24 26 Description: Chronic respiratory Acute-on-chronic Unopposedchronic Lossof compensatory Unopposedacute acidosis with corn- respiratoryacidosis; metabolicalkalosis; metabolicalkalosis; respiratoryaci- pensatory metabolic prior compensation alkalemia "normal" acid-base dosis; acidemia atkalosis; normal pH inadequate;acidemia status; normal pH

ance returns to "normal", such that when weaning is at- recoil pressure of the respiratory system, at which the tempted the patient may be unable to maintain the V A inward elastic recoil forces of the lung equal the oppos- necessary to keep PaCO 2 normal, and once again devel- ing outward recoil forces of the chest wall [35]. In pa- op acute respiratory acidosis. tients with airflow limitation, such as in COPD, the The goal of ventilatory management with respect to lung may not empty completely prior to the next in- acid-base status should therefore be homeostasis, with spiratory effort, resulting in end-expiratory lung maintenance of the patient's previous compensatory volumes higher than FRC [34, 36-39]. This results in pro- state. This can be accomplished by controlled hypoventi- gressive increases in lung volumes, as shown schemati- lation, attempting to keep the pH at or below 7.40. Cor- cally in Fig. 1. Trapped air increases with larger tidal rection of the initially low pH should be approached slow- volumes, increased expiratory airflow resistance and ly and "from below", allowing for acidosis and avoiding higher lung compliance (i. e., prolonged time constant) alkalosis. Indeed, allowing respiratory acidosis and fur- as well as with decreased expiratory time [38, 40]. Dy- ther HCO3- retention (permissive hypercapnia) will re- namic hyperinflation denotes the progressive increase duce the work of breathing during weaning. With the ad- in lung volumes consequent to this incomplete emptying. vent of NPPV it is now possible to wean patients from in- Auto-PEEP (endogenous positive end-expiratory pres- tensive care unit (ICU) ventilators to portable positive sure or intrinsic PEEP) refers to the state of elevated airway pressure devices [11-13] that may be used inter- net static recoil pressure of the respiratory system at end mittently after discharge from th ICU. This strategy will expiration that occurs in the dynamically hyperinflated help the patient to maintain a more normal V a and lower lung [34, 39, 41, 42]. This elevated end-expiratory alveo- PaCO2, and represents a viable alternative strategy. lar pressure has also been called occult PEER because it The elevated VJV T caused by air trapping (dynamic is not registered on the ventilator's pressure manometer hyperinflation) and emphysema presents another acid- (since the manometer communicates with atmospheric base challenge. Often the COPD patient has a persis- pressure during exhalation) [37, 38, 43]. tent respiratory acidosis even after the initiation of me- Dynamic hyperinflation or auto-PEEP can be con- chanical ventilation employing standard or high minute ceptualized using the now famous waterfall analogy volume. Indeed, as the respiratory rate and tidal volume (See Fig, 2) [38, 44, 45]. Airflow limiation occurs at a cri- are increased, the PaCO2 may actually rise due to pro- tical closing point in the airways, at which there is a gressive dynamic hyperinflation consequent upon re- back-up of pressure in the airways that is analogous .to duced expiratory time in a system with severe airflow the crest of a waterfall. Pressure drops across the critical obstruction [31]. Controlled hypoventilation and per- closure point as water drops down the face of a water- missive hypercapnia [32, 33] are well-tolerated even at fall. Airway pressure at the mouth is represented by pH levels as low as 7.15-7.20, and tend to reduce the the water downstream of the waterfall. If the down- above risks [34]. This strategy buys time for the princi- stream water level rises it will not influence that at the pal pharmacologic interventions, such as corticoster- crest of the waterfall until the level downstream rises oids, bronchodilators and antibiotics, to take effect. higher than the waterfall itself. Therefore, adding external pressure or extrinsic-PEEP will not affect alveolar pressure (or lung volume) until it is greater than the actual pressure proximal to the critical closure point. Dynamic hyperinflationand auto-PEEP The waterfall analogy illustrates three concepts. In persons breathing at normal rates, functional residual First, the extrinsic PEEP needed to increase overall capacity (FRC) is defined by the point of zero net static lung volume (and hence alveolar pressure) will repre- 901

Airway obstruction sent an approximation of auto-PEEP (i. e., the height of Lung the waterfall). Second, adding less extrinsic PEEP than volume auto-PEEP will not increase overall lung volume and, third, adding extrinsic PEEP in excess of auto-PEEP will increase lung volumes. Importantly, the addition of extrinsic PEEP that is slightly less than or equal to the measured auto-PEEP level may still increase lung vol- FRC , , , , , ume as there may be areas of inhomogeneity within the Insp. Exp. lung [46]. ti te Time Dynamic hyperinflation associated with expiratory Fig.1 The lung volumes of successive mechanically ventilated flow limitation as discussed here occurs at tidal breath- breaths are plotted over time in a normal patient and in a patient ing even in paralyzed patients (thus eliminating auto- with progressive dynamic hyperinflation. In the normal lung the PEEP caused by excessive expiratory abdominal muscle entire tidal volume (VT) is exhaled and lung volume returns to activity [47] and high respiratory rates) [48]. In the functional residual capacity (FRC) prior to the subsequent breath. In the patient with airflow obstruction there is incomplete empty- COPD patient this is attributable to dynamic airways ing of V Twith each breath, resulting in progressive dynamic hyper- collapse, increased airway resistance from airways mu- inflation. Vtrap ~d is the volume of trapped air in the dynamically cus, edema and smooth muscle contraction, and the hyperinflated ~ung; VEI is the volume at end-inspiration, and is the overall reduction in elastic recoil of the emphysematous sum of V T and Vtrappe d (Used with permission. From Tuxen [33] lung.

A. Detection of auto-PEEP and dynamic hyperinflation C V +1o The clinician must maintain a high level of suspicion and A frequently measure or estimate the level of auto-PEEP to avoid the complications of dynamic hyperinflation, B. which include hypotension and hemodynamic collapse, barotrauma and increased work of breathing. Auto- PEEP and dynamic hyperinflation should be suspected in all patients with COPD undergoing mechanical venti- PEEP O lation, but especially under the circumstances outlined C. in Table 2. The most practical method of measuring auto-PEEP is by end-expiratory occlusion. This measurement of static auto-PEEP can be accomplished by manually occluding the ventilator expiratory port at end-expiration ~ External PEEP8 and temporarily deferring the next inspiration, or by ac- D. tivating an end-expiratory pause button in ventilators equipped with this feature [37, 43]. At end-expiration the pressure at the airway opening is measured as zero, but after occlusion the trapped air in the alveoli equili- brates with that in the airways beyond the critical clo- External PEEP 12 sure point, thus permitting detection of positive pres- Fig.2 Dynamic hyperinflation or auto-PEEP can be conceptua- sure (see Fig. 3). This positive pressure represents the lized using the waterfall analogy. (A) Airflow limitation occurs at summation of auto-PEEP in areas of lung with normal, a critical closure point in the airways resulting in a back-up of pres- short and long time constants, provided that the occlu- sure in the airways; an alveolar pressure of 10 cm H20 is depicted in this illustration of an alveolar-airway unit. This is analogous to sion time is long enough to allow emptying of those the crest of a waterfall (B). The pressure drops across the critical lung units with the longest time constants. If the patient closure point as the water level drops down the face of the water- makes an inspiratory effort, or uses excessive abdominal fall. The airway pressure at the mouth is represented by the water muscle expiratory effort, this end-expiratory occlusion downstream of the waterfall. If the downstream water level rises measurement is difficult to interpret [49]. Measure- (C, as an extrinsic PEEP of 8 cm H20 ) it will not affect the water ments in the deeply sedated or paralyzed patient are, level at the crest of the waterfall until the water level downstream rises higher than the waterfall itself (D, extrinsic PEEP of 12 cm therefore, the most reliable. H20) If the ventilator incorporates a graphics display, auto- PEEP can be detected (although not conveniently quantified) by observing that the expiratory flow does not 902

Table 2 Dynamic hyperinflation and auto-PEEP during mechanical ventilation 10 0 . 10 .. ,0. Clinical circumstances in which auto-PEEP should be suspected Unexplained tachycardia, hypotension or pulseless electrical activity, especially on initiation of mechanical ventilatory sup- End-Expiration End-Expiratory Occlusion port Patient appears to be working very hard to trigger each breath Patient's inspiratory efforts do not trigger airflow from the ventilator every time Clinical observation of active expiration or wheezes that continue to the onset of inspiration Fig.3 End-expiratory occlusion pressure technique for quanititat- If monitoring with a graphics display, expiratory flow is still pre- ing auto-PEER The illustration depicts an alveolar-airway unit sent at the initiation of the next breath with 10 cm H20 of auto-PEEP proximal to a critical closure point. Measurement or estimation of auto-PEEP At end-expiration the pressure at the airway opening will be mea- Determination of end-expiratory occlusion pressure: manually sured as zero (left side of figure; asterix), because the manometer occlude expiratory port at end-expiration or activate end-expi- is open to atmospheric pressure during exhalation. A static mea- ratory pause button on ventilator. A 1-3 s occlusion allows time surement of the trapped alveolar gas (static auto-PEEP) can be ac- for the trapped air to equilibrate across most obstructed airways. complished by manually occluding the expiratory port at end-ex- (Only applicable in patients who are not actively attempting to piration (right side of figure) or by activating an end-expiratory breathe) pause button on the ventilator. After occlusion of the expiratory Measurement of expired volume (VEx) during a 30-50 s apnea. port the trapped air in the alveoli will equilibrate with the airways Subtraction of tidal volume from V H will give the volume of beyond the critical closure point, resulting in a deflection of posi- trapped air (Vei - Vr = Vtrapped) (Requires relaxed patient with- tive pressure measured after occlusion out inspiratory effort) Direct measurement of pleural (esophageal) pressure with an esophageal balloon and pressure transducer Measurement of peak inspiratory pressure (PIP) and plateau the end-expiratory positive alveolar pressure and elastic pressure (Pplat) while increasing dialed-in PEEP by 3-cm H~O recoil, of the respiratory system (i. e. auto-PEEP). As is increments; as long as PIP and Pplat do not change, set PEEP is the case with the end-expiratory occlusion technique, below auto-PEEP; if PIP and/or Pplat go up with the addition of external PEER the mean auto-PEEP level has been exceeded. abdominal muscle contraction may result in overestima- (Only PIP can be measured if patients are actively attempting to tion of auto-PEEP [47]. These techniques for the mea- breathe) surement of auto-PEEP are summarized in Table 2. During simultaneous recording of airway flow and pressure tracings, measurement of applied pressure required to initiate inspiratory flow (Requires relaxed patient without spontaneous inspiratory effort) Complications of dynamic hyperinflation/auto-PEEP Dynamic hyperinflation and auto-PEEP may cause cardiovascular compromise and barotrauma, and may sub- reach zero prior to inspiration (see Fig. 4). To quantify stantially increase the patient's work of spontaneous auto-PEEP associated with such extended expiratory breathing. These processes can all present insidiously flow, Rossi et al. [41] recorded airway pressure and and delay liberation from mechanical ventilation, pre- flow simultaneously, and measured the pressure re- disposing the patient to increased morbidity and mortal- quired to initiate inspiratory flow. This applied pressure ity. counterbalances the elastic recoil present at the dynamically elevated lung volume and represents auto-PEEP [41, 50]. Cardiovascular compromise Dynamic hyperinflation can be further quantified by measuring expired volume during a period of apnea in With dynamic hyperinflation lung volume and intratho- a paralyzed patient [51, 52]. After a period of tidal racic pressure increase, venous return is impaired and breathing apnea is imposed for 30-50 s, allowing expira- the right ventricle and pulmonary veins are mechanical- tion to occur until there is no further elevation in mea- ly compressed [39]. This reduces left ventricular preload sured airway pressure with occlusion of the expiratory and cardiac output. Central venous and pulmonary ar- port. The expired air is measured (called VEI for end-in- tery occlusion pressures are elevated, reflecting inspiratory volume) and when subtracted from tidal vol- creased intrathoracic pressure rather than increased in- ume provides an estimation of trapped air (see Fig. 1). travascular volume. The combination of high filling Finally, an esophageal balloon can be used to mea- pressures, reduced cardiac output and hypotension may sure dynamic auto-PEEP [53, 54]. The negative esopha- be mistakenly diagnosed as left ventricular failure. Con- geal pressure generated prior to the initiation of inspira- tinued dynamic hyperinflation may result in pulseless tory flow represents the pressure needed to overcome electrical activity (PEA) and cardiac arrest [37, 55-60]. 903

ly in patients with COPD and pre-existing hypercapnia 3 - [60]. The transition from manual to mechanical ventilation carries the iatrogenic hazards of attempting to ap- o /- ply the usual tidal volumes and respiratory rates em- .._1 ployed in acute respiratory failure and ill-advised at- O tempts to drive the PaCO 2 down to the normal range, interventions that further reduce expiratory time. It is instructive to consider case reports of patients -3- with COPD who develop PEA and do not respond to aggressive resuscitation. In several cases, after resuscita- Presence of Auto-PEEP No Auto-PEEP tive efforts had been discontinued, the arterial line be- Fig,4 Ventilator graphics display of flow during sequential me- gan to pick up a pulse [55-58]. Discontinuation of mechanically ventilated breaths in the presence and absence of auto- chanical ventilation allowed full exhalation to occur PEER Auto-PEEP can be detected (although not conveniently and intrathoracic pressure to decrease, resulting in en- quantified) by observing expiratory flow that does not reach zero hanced venous return and restoration of cardiac output prior to inspiration [37]. A recent review of 89 in-hospital cardiac arrests, 35 of which involved PEA, revealed no discernible etiol- ogy in 18, and 13 (74%) of these patients were subse- c 5.0] quently found to have COPD by history, pulmonary 4.37 "E 3.0 function testing or autopsy [59]. By contrast, only 11% , * d T 2.62 2.81 of the remaining patients had COPD [59]. This suggests 1.0 that unrecognized auto-PEEP may be a common cause of PEA. 150 - Dynamic hyperinflation and auto-PEEP must be E 100 considered as potential causes of hypotension in the me- E BP chanically ventilated patient with COPD, as well as in 50 the setting of cardiac arrest with PEA. A 30-s interrup- 30- tion of positive-pressure ventilation can be diagnostic, ~ i1~"~ ""I""~ '1" Wedge as prolonged expiration and reduction in intrathoracic E 15- pressure relieve hemodynamic embarrassment [34]. Fig- E ~ ESOPH ure 5 illustrates the hemodynamic effects of dynamic

OT i hyperinflation in a patient with COPD, and improve- 0 2? 40 60 s ment during 30 s of apnea [37]. 'PPV --I I 'PPV Fig,5 Illustration of the hemodynamic effects of dynamic hyperin- Barotrauma flation in a patient with COPD, with improvement during 30 s of apnea. Discontinuation of intermittent positive pressure ventila- Dynamic hyperinflation results in overdistention of tion (IPPV) results in increased cardiac output (QT), blood pres- fragile emphysematous lung parenchyma, which may sure (BP), pulmonary capillary wedge pressure (WEDGE) and esophageal (ESOPH) pressure. (Used with permission. From lead to alveolar disruption and extra-alveolar air (clini- Pepe and Marini [37]) cal barotrauma). Following alveolar rupture, air dissects into the pulmonary interstitium, follows the broncho- vascular sheath to the mediastiunum and from there en- ters the pleura and other tissues. A comprehensive dis- The patient with COPD may be at greatest risk for cussion of pneumothorax and bronchopleural fistula this complication immediately following intubation. during mechanical ventilation is beyond the scope of The urgency of the situation often leads to overzealous this article and the reader is directed to other sources manual ventilation prior to connection to the ventilator: for a more complete review [61-64]. large tidal volumes and rapid respiratory rates increase Prevention of clinical barotrauma centers on the con- lung volume and shorten expiratory time, preventing trol of auto-PEER by extending expiratory time as well adequate exhalation and potentiating dynamic hyperin- as by limiting high tidal volumes and maximum alveolar flation. In the setting of non-elective emergency intuba- distention [62]. The commonly used strategy of limiting tion, the reduction in cardiac output associated with dy- peak inspiratory pressure (PIP) to 50 cm H20 or less de- namic hyperinflation is often compounded by volume rives from the observation of a reduced incidence of depletion and sedation [34]. Hypotension may occur in barotrauma at these controlled pressures in asthmatics up to 25 % of all emergency intubations, more frequent- [65, 66]. Unfortunately, PIP reflects not only lung com- 904

Fig.6 Effect of extrinsic PEEP Zero Applied PEEP 8 cm H20 Applied (Extrinsic) PEEP on patient triggering effort in the presence of auto-PEER (A) Il- End-Expiratory + 10 cm H20 Auto-PEEP lustration of an alveolar-airway End-Expiratory + 10 cm H20 Auto-PEEP + 8 cm H20 Applied PEEP unit at end expiration with + 10 cm H20 alveolar pressure and zero pressure at the airway 0 +8 +8 distal to the critical closure point. A A Initiating inspiratory flow re- CContinued FI0wat End-Expirati0n Continued Flow at End-Expiration quires reversing this pressure gradient so that alveolar pressure is less than airway pressure. If end- -lo Inspiratory Effort -2 Insplratory Effort expiratory alveolar pressure remains at 10 cm H20 then an intrapleural pressure of less than +8 +8 - 10 cm H20 is necessary to drop A A alveolar pressure to less than at- No Flow No Flow mospheric pressure and initiate -lO -2 inspiratory flow. (B) Carefully applying extrinsic PEEP (here, Increased Inspiratory Effort Increased Inspiratory Effort -11 -3 8 cm H2 O) will increase the airway pressure at the airway opening and reduce the pressure gra- -1 ~ o +8 +8 dient required to reverse flow on A /N inspiration Row Begins FI0w Begins A C-11 B -3 pliance but also flow resistive properties (airway and en- can only be achieved with deep sedation, usually with dotracheal tube resistance and peak inspiratory flow). neuromuscular blockade. Indeed, in asthmatics high PIP alone is not a reliable in- dicator of the risk of barotrauma [67, 68]. Increasing peak inspiratory flow to reduce inspiratory time is thus Effects on work of breathing (WOB) a reasonable strategy to prevent dynamic hyperinflation. Although increased peak inspiratory flow raises The impact of auto-PEEP on patient WOB, both on and PIP as measured at the airway opening, it may actually off the ventilator, is significant. With dynamic hyperin- reduce alveolar distension by allowing more expiratory flation, at end-expiration there will be a significant pres- time, and paradoxically reduce the risk of pneumotho- sure gradient between the alveolar pressure and pres- rax. sure in the airway distal to the critical closure point. Identifying clinical assessments that actually reflect Spontaneous inspiration requires reversing this pressure alveolar distention and limit the magnitude of this phe- gradient such that alveolar pressure is less than the air- nomenon are appropriate goals. Plateau pressure way pressure and flow reverses. If end-expiratory alveo- (Pplat) is measured by occluding the proximal airway lar pressure remains at 10 cm H20, intrapleural pres- at end inspiration, allowing the peak proximal airway sures must exceed - 10 cm H20 in order to reduce the pressure to equilibrate across airways with high resis- alveolar pressure to less than atmospheric and initiate tance. PIP falls to a lower post-occlusion pressure that inspiratory flow (Fig.6A). Therefore, auto-PEEP re- more accurately reflects the elastic recoil of the respira- presents an inspiratory threshold load that must be tory system and thus alveolar distention [34]. In pa- overcome if the patient is to breathe spontaneously or tients with COPD, PIP is highly dependent on the de- trigger the ventilator [39]. Furthermore, this must occur gree of airflow resistance and peak flow while Pplat is at higher lung volumes, such that inspiration occurs in a independent of flow resistive properties, unless the less compliant portion of the pressure-volume curve, pause time is inadequate to allow complete equilibra- where there is a greater inward elastic recoil of the over- tion or the airways are completely obstructed. It has expanded chest wall [38, 70]. been recommended that Pplats be kept below 30 cm The mechanically ventilated patient with dynamic hy- H20 [69], although this remains theoretical [34]. Alter- perinflation must first overcome this inspiratory thresh- natively, limiting end-expiratory volume (VEI - see old load and, depending on the triggering mechanism of Fig. 1) to less than 1.4 1 [68] may be relevant for patients the ventilator, further reverse flow (flow-triggered) or with COPD, in that hypotension and barotrauma are lower the airway pressure (pressure-triggered) to initiate uncommon in patients with severe asthma when V H is delivery of a breath. This can be detected at the bedside less than this. Unfortunately, the measurement of VEI by observing chest wall expansion and accessory muscle requires a 30-60 s complete exhalation which clinically activity that do not trigger a ventilated breath [71]. Air- 905

o 20. Table 3 General principles of mechanical ventilation in patients with chronic obstructive pulmonary disease m E o O- ~ ~ ~ ~ ~...._~ Rest patient while pharmacotherapy takes effect Provide full ventilatory support, regardless of ventilation mode employed (e. g. enough ventilation to keep total respiratory rate below 30 breaths/min) Prevent dynamic hyperinflation (auto-PEEP) and its complications Fig.7 Illustration of simultaneous airway (PAw) and esophageal Increase expiratory time (PEs) pressure tracings in a patient with dynamic hyperinflation, Tidal volume 5-8 ml/kg revealing negative inspiratory excursions that do not trigger a High peak inspiratory flow (70-100 l/rain) breath alternating with triggered breaths. If end-expiratory alveo- Low respiratory rate to avoid relative hyperventilation lar pressure (i. e. auto-PEEP) remains at 10 cm HaO then, the pa- Non-compressible ventilator tubing tient must reduce intrapleural pressure (measured by an esopha- Sedation as required geal manometer-Pes) to less than - 10 cm HzO to drop alveolar Add extrinsic PEEP at 80 % of auto-PEEP level to reduce pa- pressure to less than atmospheric pressure and initiate inspiratory tient triggering effort flow. The mechanically ventilated patient with dynamic hyperinfla- Provide controlled hypoventilation (permissive hypercapnia) tion must first overcome this inspiratory threshold load and then, Avoid alkalemia, allowing patient to maintain compensatory depending on the triggering mechanism of the ventilator, further metabolic alkalosis reverse flow (flow-triggering) or lower the airway pressure (pres- Provide sufficient ventilation to maintain pH > 7.15-7.20 sure-triggering) prior to delivery of a breath Resulting PaCO 2 value is less important than avoidance of alkalemia Bicarbonate infusion may be necessary at very low pH if cardiovascular instability is present way and esophageal pressure tracings reveal negative in- Ventilator mode used is relatively unimportant if above principles spiratory excursions that do not trigger a breath, alter- are followed nating with those that do (see Fig. 7) [72]. Carefully ap- Assist-control ventilation (A/C, AMV): Use high inspiratory flow rate plying extrinsic PEEP increases the proximal airway Minimize patient triggering effort pressure and reduces the pressure gradient required to Use sedation if necessary to reduce minute ventilation reverse flow on inspiration (see Fig. 6B) [38, 40-42, 53, Synchronized intermittent mandatory ventilation (SIMV): 73]. Applied PEEP can be titrated to a level at which ev- Use high inspiratory flow rate ery inspiratory effort triggers a breath, resulting in sharp Monitor patient's total rate as index of comfort (should be reductions in the patient's WOB. < 30/min) Sedate patient if necessary Patients with emphysema, characterized by compli- Pressure support ventilation (PSV): ant or floppy airways poorly tethered by damaged elas- May be more comfortable than other modes, at least for some tic fibers, develop an early "equal pressure point" as patients the positive extramural pressure exceeds the elastic re- For safe use patient's ventilatory drive must remain intact coil forces of the airway and the positive intramural air- Adjust inspiratory pressure to keep respiratory rate way pressure. Theoretically, the application of extrinsic < 30 breaths/rain Pressure control ventilation (PCV): PEEP less than the original level of auto-PEEP should Reduce inspiratory time (e. g. 25 %) to maximize expiration serve to prevent this early dynamic airway closure at Adjust inspiratory pressure to keep respiratory rate < 30/min the equal pressure point by maintaining a positive air- Sedate patient if necessary way pressure that counterbalances the positive extra- Auto-PEEP will have different effects on different ventilator modes mural pressure that surrounds the airways [48]. With AMV and SIMV: increase in Pplat and PIP with no change Unfortunately, the concept that applied PEEP thus in tidal volume "stents" open airways and facilitates lung emptying is With PSV and PCV: reduction in delivered VTwith no change in not supported by clinical studies. The application of ex- Pplat and PIP ternal PEEP rarely leads to actual reductions in lung volume [42, 46, 74, 75]. As the level of applied PEEP approaches that of auto-PEER lung volume actually in- It is therefore reasonable judiciously to apply PEEP creases [34, 42, 46, 53, 74, 75]. This is in keeping with to about 80 % of the measured auto-PEEP level, to re- the waterfall analogy: as the downstream water rises duce WOB associated with patient-initiated mechanical above the dam, the water backs up behind the dam. In ventilation. However, there is no rationale for its use fact, the greatest risk of applied PEEP in the COPD pa- during controlled mechanical ventilation when there is tient is inducing further hyperinflation with cardiovas- no patient inspiratory effort, or in an attempt to "stent" cular compromise. Progressive increments of PEEP open airways to reduce lung volume. compared with zero PEEP induce hemodynamic impairment when the levels of applied PEEP exceed 85 % of the measured auto-PEEP [46]. 906

Principles for mechanical ventilation of the COPD patient therapist is cognizant that increases in duty cycle will increase dynamic hyperinflation. Once a patient with acute respiratory failure complicat- There has been considerable debate about whether ing severe COPD has been intubated and placed on a nebulizers are more effective than MDIs in ventilated ventilator, the primary objective is to take over the patients. Numerous studies support the efficacy of work of breathing and rest the respiratory muscles, al- MDIs provided spacer devices are used, the MDI is ac- lowing time for the primary therapies (corticosteroids, tuated immediately prior to inspiratory flow with a bronchodilators, antibiotics, diuretics, etc.) to take ef- 30 s-1 min pause between actuations, and the above fect. Ventilator strategies then focus on avoiding com- general recommendations are adhered to [82, 83]. Using plications and weaning the patient as soon as possible. these techniques, four puffs (90 ~g/puff) of albuterol re- Table 3 presents an overview of the basic principles of duced airway resistance to the same degree as 8 and ventilatory management necessary to achieve these 16 puffs, without the rise in heart rate that occurred goals. If these strategies are adhered to, the actual with the higher doses [83]. The advantage of the MDI mode of mechanical ventilation chosen is not of primary is the lower cost, freedom from contamination and, pos- importance. It is important to utilize a mode that is fa- sibly, the ease of dosing [77]. The advantage of nebu- miliar to the clinicians that care for the patient, as com- lized bronchodilators is the therapist can simply attach plications such as dynamic hyperinflation and pneumo- the nebulizer into the inspiratory limb of the ventilator thorax are manifest in different ways on pressure-versus circuit. volume-targeted modes (see Table 3). Sedation and occasionally paralysis may be required The complications of dynamic hyperinflation can be to reduce the minute ventilation. However, the use of avoided by timely suspicion, detection and therapy. neuromuscular blocking agents should be limited, to Control of dynamic hyperinflation is primarily achieved avoid precipitating the necrotizing myopathy associated by facilitating adequate lung emptying by reducing in- with these agents and corticosteroids [84]. Short acting spiratory, and prolonging expiratory, time on the venti- agents such as propofol, fentanyl or midazolam may al- lator. Reducing overall minute ventilation most effec- low for more rapid weaning, but there are few data to tively increases expiratory time; tidal volumes of support one agent over the other. 5-8 ml/kg and rates of 8-10 breaths/min are recommended. Inspiratory time can be shortened by increasing the inspiratory flow rate, which will increase peak Weaning from mechanical ventilation airway pressure although alveolar or plateau pressures will be unaffected. The use of non-compressible ventila- Weaning is often difficult in the patient with COPD [85, tor tubing will also reduce inspiratory time by reducing 86] because of the increased elastic and resistive work- the volume the ventilator must deliver in order to reach loads [87]. The patient with COPD is also subject to the set (corrected) V T [76]. non-respiratory stresses, including coronary artery dis- Beta-adrenergic and anticholinergic bronchodilators ease and left ventricular dysfunction, malnutrition and can be effectively delivered to the mechanically venti- iatrogenic insults such as residual sedation, volume lated patient via small volume nebulizers (SVN) or me- overload and disruption of acid-base status [88]. Table 4 tered-dose inhalers (MDI). These medications, when presents a summary of management strategies for wean- dosed and delivered effectively, will reduce airway resis- ing the COPD patient. The reader is further directed to tance (measured by Ppeak-Pplat/airflow) and hyperin- recent comprehensive reviews of respiratory and non- flation [77]. The delivery will be maximized by a num- respiratory aspects of weaning [87-91]. ber of factors. First, medication should be delivered at The overriding principles should be early weaning a distance from the endotracheal tube in the inspiratory and avoidance of complications that adversely impact limb of the ventilator circuit to avoid impaction and de- this process. Three critical factors deserve special men- position of larger aerosol particles [78]. Second, humidi- tion. Alkalemia should be avoided, in that imposing re- fication of the ventilator circuit reduces aerosol delivery spiratory acidosis and HCO 3- retention will allow wean- by one-third to one-half, probably by increased particle ing to occur at a lower V A. Secondly, excessive sedation size resulting in particle impaction in the circuit should be avoided and short acting agents used when [79-81]. Finally, the ventilator settings will affect deliv- possible. Propofol has been shown to decrease the ery; in a lung model, delivery was enhanced by sponta- duration of ICU stay (and costs), but use it in the neous breathing (CPAP mode), larger tidal volumes knowledge that high dose propofol has significant fat and an increase in duty cycle (total inspiratory time/ calories [92, 93]. Thirdly, the work of breathing must duration of total breathing cycle) [79]. Many authors re- be minimized during weaning. Maintain enough sup- commend a breath hold after an MDI actuation to in- port so that the patient's total respiratory rate is less crease duty cycle. This recommendation is reasonable than 30-35 breaths/min with adequate tidal volumes provided dynamic hyperinflation is modest and the (e. g. > 300 ml). Trials of spontaneous ventilation are 907

Table 4 Weaning from ventilatory support cult to design and perform this form of clinical research, Reduce the patient's work of breathing and probably no one method of weaning is intrinsically Patient factors: superior to another. Aggressive use of bronchodilators and steroids A balance must be found between imposing weaning Ventilator factors: delays by overcautious reductions in support (such as Optimize inspiratory flow and sensitivity of triggering system slowly reducing the level of pressure support or the Add extrinsic (applied) PEEP to 80-85 % of auto-PEEP to reduce triggering effort number of mandatory volume breaths) and rapid unmo- Allow hypercapnia to persist; avoid alkalosis nitored withdrawal of support in the failing patient. A Consider addition of 5-8 cm H~O inspiratory pressure support reasonable approach is to reduce the amount of ventila- during trials of spontaneous breathing to reduce deleterious tory support progressively by whatever mode the clini- effects of endotracheal tube resistance cian prefers, while ensuring that the patient is not over- Rest patient with full support when dyspneic and during sleep working, as identified by a respiratory rate of more periods than 30-35 breaths/min and VT less than 250-300 ml, Maximize non-respiratory factors until a minimal level of support is achieved. Adding dai- Provide adequate nutritional support Optimize treatment of volume overload, coronary artery ly trials of spontaneous breathing (whether via T-piece, disease and left ventricular dysfunction continuous positive airway pressure or low-level in- Correct electrolyte and metabolic disorders spiratory pressure support) ensures that the slower Avoid excessive sedation and paralysis weaning methods do not mask the patient's readiness Maximize psychological factors for extubation [94, 96]. Obtain patient's understanding and cooperation Weaning by extubating the patient and applying Mobilize patient; sitting in chair is optimal NPPV is ~ newer strategy that has been reported to be Allow sleep at night successful iri many patients with COPD [11-13]. Success Oral feeding Diversion and entertainment; liberal family visitation rates approximate 80 %, which mirror the success rates of NPPV used for post-extubation failure [97, 98]. Wean as soon as possible Usually can wean within 1-2 days The indications for and timing of tracheotomy in me- Maintain PaO 255-65 mmHg (saturation 85-90 %) when at- chanically ventilated patients are the subject of much tempting weaning debate [99-101]. A tracheostomy offers~ the advantages PSV, SIMV with PSV and trials of spontaneous breathing with of reducing laryngeal injury, allowing the patient to T-piece, CPAP or minimal PSV are all reasonable approaches, communicate and move more freely with a lessened taking care to avoid excessivework of breathing and signs of risk of self-extubation and facilitates oral nourishment, fatigue Consider use of non-invasive positive-pressure ventilation as a pulmonary toilet and early ICU discharge. Complica- transitional procedure in difficult-to-wean patients tions include tracheal stenosis, a greater incidence of bacterial colonization [102], and postoperative complications such as pneumothorax, tracheo-innominate fistula, pneumothorax and death [100, 101]. Good clinical reasonable so long as the patient is not left to struggle. data are lacking concerning the role of tracheostomy in The clinican should consider adding low levels of in- the difficult-to-wean patient with COPD. The inherent spiratory pressure support to overcome endotracheal advantages to the patient, such as increased oral nutri- tube resistance and low levels of extrinsic PEEP to re- tion, ambulation and psychological factors, are again duce the muscular effort required to trigger the ventila- balanced by an increase in surgical complications as tor [89]. well as the risk of early transfer to a service that is less With respect to the actual mode of weaning em- equipped to deal with this population's unique ventila- ployed, two recent studies evaluated weaning techni- tor problems. However, it should be noted that a recent ques in populations of difficult-to-wean patients and retrospective review of 259 patients with severe COPD came to differing conclusions. Brochard et al. [85] found (mean FEV 1 0.73 1) who had tracheostomies for at least that pressure support weaning was superior and Esteban 1 year revealed an actuarial survival rate of 70% at et al. [94] determined that intermittent trials of sponta- 2 years, 44 % at 5 years and 20 % at 10 years [103]. Tra- neous breathing via a T-piece were superior to pressure cheostomy and home mechanical ventilation may prove support weaning. Weaning via intermittent mandatory to play an important role in the management of the diffi- ventilation was found to be less effective than either cult-to-wean patient, but more data are sorely needed, pressure support or T-piece in both studies. Careful re- especially with the advent of NPPV. A protocol that ran- view of these trials suggests that differing study design domized difficult-to-wean patients to standard therapy, elements, such as the level of pressure support em- early or late tracheotomy, or early or late extubation to ployed prior to extubation and criteria selected to assess NPPV, would help to answer many of these questions. patient tolerance of weaning, may have affected the outcome of the technique employed [87, 95]. It is very diffi- 908

Outcome database which disclosed ICU, hospital and 1-year mortality rates of 16 %, 32 %, and 50 %, respectively [107]. The overall prognosis of the patient with COPD who re- Nevertheless, it is clear that the patient with severe quires mechanical ventilation for acute-on-chronic re- COPD in acute respiratory failure can survive mechani- spiratory failure is poor and dependent on premorbid cal ventilation and be discharged from the hospital. How- factors such as the degree of airflow obstruction and ever, such patients continue to have a high risk of further functional status [104, 105]. Weiss and Hudson [105] re- exacerbations, resulting in frequent admissions and mor- viewed 11 studies with an average hospital mortality tality in excess of 50 % at I and 2 years [104-108]. rate of 43 %. Two other studies reported ICU mortality Therefore, the physician and patient should share a of 27 % and a 1-year mortality of 62 % [104] and ICU clear understanding that providing aggressive ICU and mortality, hospital mortality and 2-year mortality rates ventilator support is reasonable, but that discussions of of 50 %, 53 %, and 58 %, respectively [106]. These data end-of-life issues and possible limitations of duration are in keeping with a recent review of the APACHE III and level of aggressive care are necessary.

References 1, Pingleton SK (1988) Complications of 10. Corrado A, Gorini M, Villella G, et al 18. Brochard L, Isabey D, Piquet J, et al acute respiratory failure. Am Rev Re- (1996) Negative-pressure ventilation (1990) Reversal of acute exacerbations spir Dis 137:1463-1493 in the treatment of acute respiratory of chronic obstructive lung disease by 2. Pierson DJ (1990) Complications of failure: an old noninvasive technique inspiratory assistance with a face mechanical ventilation. Curr Pulmo- reconsidered. Eur Respir J 9: mask. N Eng J Med 323:1523-1530 nol 11:19-46 1531-1544 19. Goldberg R Reissmann H, Maltais F, 3. Brochard L, Mancebo J, Wysocki M, 11. Udwadia ZF, Santis GK, Steven MH, et al (1995) Efficacy of noninvasive et al (1995) Noninvasive ventilation Simonds AK (1992) Nasal ventilation CPAP in COPD with acute respiratory for acute exacerbations of chronic ob- to facilitate weaning in patients with failure. Eur Respir J 8:1894-1900 structive pulmonary disease. N Engl J chronic respiratory insufficiency. 20. Confalonieri M, Aiolfi S, Gandola L, Med 333:817-822 Thorax 47:715-718 et al (1994) Severe exacerbations of 4. Weiss SM, Hudson LD (1994) Out- 12. Restrick LJ, Scott AD, Ward EM, et al chronic obstructive pulmonary disease come from respiratory failure. Crit (1993) Nasal intermittent positive- treated with BiPAP by nasal mask. Re- Care Clin 10:197-215 pressure ventilation in weaning intu- spiration 61:310-316 5. Curran FJ (1981) Night ventilation by bated patients with chronic respiratory 21. Meduri GU, Turner RE, Abou-Shala body respiratory for patients in chron- disease from assisted intermittent, po- N, et al (1996) Noninvasive positive ic respiratory failure due to late stage sitive-pressure ventilation. Respir pressure ventilation via face mask: Duchenne muscular dystrophy. Arch Med 87:199-204 first-line intervention in patients with Phys Med Rehabil 62:270-274 13. Nava S, Ambrosino N, Clini E, Prato acute hypercapnic and hypoxemic re- 6. Garay SM, Turino GM, Goldring RM M, Orlando G, Vitacca M, et al (1998) spiratory failure. Chest 109:179-193 (1981) Sustained reversal of chronic Noninvasive mechanical ventilation in 22. Confalonieri M, Parigi R Scartabellati hypercapnia in patients with alveolar the weaning of patients with respira- A, et al (1996) Noninvasive mechani- hypoventilation syndromes: long-term tory failure due to chronic obstructive cal ventilation improves the immedi- maintenance with noninvasive noctur- pulmonary disease. A randomized, ate and long-term outcome of COPD nal mechanical ventilation. Am J controlled trial. Ann Intern Med 128: patients with acute respiratory failure. Med 70:269-274 721-728 Eur Respir J 9:422-430 7. Goldstein RS, Molotiu N, Skrastins R, 14. Ferguson GT, Gilmartin M (1995) CO~ 23. Vitacca M, Clini E, Rubini F, et al et al (1987) Reversal of sleep-induced rebreathing during BiPAP ventilatory (1996) Non-invasive mechanical venti- hypoventilation and chronic respira- assistance. Am J Respir Crit Care lation in severe chronic obstructive tory failure by nocturnal negative- Med 151:1126-1135 lung disease and acute respiratory fail- pressure ventilation in patients with 15. Lofaso F, Brochard L, Touchard D, et ure: short- and long-term prognosis. restrictive ventilatory impairment. al (1995) Evaluation of carbon dioxide Intensive Care Med 22:94-100 Am Rev Respir Dis 135:1049-1055 rebreathing during pressure support 24. Bott J, Carroll MR Conway JH, et al 8, Shapiro SH, Ernst R Gray-Donald K, ventilation with airway management (1993) Randomized controlled trial of et al (1992) Effect of negative-pressure system (BiPAP) devices. Chest 108: nasal ventilation in acute ventilatory ventilation in severe chronic obstruc- 772-778 failure due to chronic obstructive air- tive pulmonary disease. Lancet 340: 16. Hillberg RE, Johnson DC (1997) ways disease. Lancet 341:1555-1557 1425-1429 Noninvasive ventilation. N Engl J 25. Pierson DJ (1992) Clinical approach to 9. Corrado A, De Paola E, Gorini M, et Med 337:1746-1752 the patient with acute ventilatory fail- al (1996) Intermittent negative-pres- 17. Kramer N, Meyer TJ, Meharg J, et al ure. In: Pierson DJ, Kacmarek RM sure ventilation in the treatment of hy- (1995) Randomized, prospective trial (eds) Foundations of respiratory care. poxic hypercapnic coma in chronic re- of noninvasive positive pressure venti- Churchill Livingstone, New York, spiratory insufficiency. Thorax 51: lation in acute respiratory failure. pp 707-719 1077-1082 Am J Respir Crit Care Med151: 1799-1806 909

26. Muir JF, Levi-Valensi P (1987) When 41. Rossi A, Gottfried SB, Zocchi L, et al 53. Petrol BS, Linegare M, Goldberg R et should patients with COPD be ven- (1985) Measurement of static lung al (1990) Continuous positive airway tilated? Eur J Respir Dis 70:135-139 compliance of the total respiratory sys- pressure reduces work of breathing 27. Meduri GU (1996) Non-invasive posi- tem during mechanical ventilation: the and dyspnea during weaning from me- tive-pressure ventilation in patients effect of intrinsic positive end-expira- chanical ventilation in severe obstruc- with acute respiratory failure. Clin tory pressure. Am Rev Respir tive pulmonary disease. Am Rev Re- Chest Med 17:513-565 Dis 131:672-677 spir Dis 141:281-289 28. American Respiratory Care Founda- 42. Smith TC, Marini JJ (1988) Impact of 54. Haluzska J, Chartrand DA, Grassino tion: Concensus conference: Noninva- PEEP on tung mechanics and work of AE, et al (1990) Intrinsic PEEP and sive positive pressure ventilation-pre- breathing in severe airflow obstruc- arterial PCO 2 in stable patients with amble and concensus statement. Re- tion. J Appl Physio165:1488-1499 chronic obstructive pulmonary dis- spir Care 42:364-396 43. Johnson B, Nordstrom L, Olsson SG, ease. Am Rev Respir Dis 141: 29. Simonds AK (1996) Negative-pressure et al (1975) Monitoring of ventilation 1194-1197 ventilation in acute hypercapnic and lung mechanics during automatic 55. Martens R Vandekerhove Y, Mullie A chronic obstructive pulmonary dis- ventilation: a new device. Bull Eur (1993) Restoration of spontaneous cir- ease. Thorax 51:1069-1070 Physiopathol Respir 11:729-743 culation after cessation of cardiopul- 30. Rosen RL, Bone RC (1990) Treatment 44. Permutt S, Bromberger-Barnea B, monary resusitation. Lancet 341:1217 of acute exacerbations of chronic ob- Bane HN (1962) Alveolar pressure, 56. Kollef MH (1992) Lung hyperinflation structive pulmonary disease. Med Clin pulmonary venous pressure, and the caused by inappropriate ventilation re- North Am 74:691-700 vascular waterfall. Med Thoracl9: sulting in electromechanical dissocia- 31. Haluzska J, Chartrand DA, Grassino 239-260 tion: a case report. Heart Lung21: AE, et al (1990) Intrinsic PEEP and 45. Pride NB, Permutt S, Riley RL, et al 74-77 arterial PaCO 2 in stable patients with (1967) Determinants of maximal ex- 57. Myles PS, Madden H, Morgan EB chronic obstructive pulmonary dis- piratory flow from the lungs. J Appl (1995) Intraoperative cardiac arrest ease. Am Rev Respir Dis 141: Physio123:646-662 after unrecognized dynamic hyperin- 1194-1197 46. Ranieri VM, Giuliani R, Cinnella G, flation. Br J Anaesth 74:340-342 32. Feihl F, Perret C (1994) Permissive hy- et al (1993) Physiologic effects of posi- 58. Rogers PL, Schlichtig R, Miro A, Pins- percapnia. How permissive should we tive end-expiratory pressure in COPD ky M (1991) Auto-PEEP during CPR. be? Am J Respir Crit Care Med 150: patients during acute ventilatory fail- An "occult" cause of electromechani- 1722-1737 ure and controlled mechanical ventila- cal dissociation? Chest 99:492-493 33. Tuxen DV (1994) Permissive hyper- tion. Am Rev Respir Dis 147:5-13 59. Lapinsky SE, Leung RS (1996) Auto- capnic ventilation. Am J Respir Crit 47. Ninane V, Yernault JC, Detroyer A PEEP and electromechanical dissocia- Care Med 150:870-875 (1993) Intrinsic PEEP in patients with tion (letter). N Engl J Med 335:674 34. Leatherman JW (1996) Mechanical chronic obstructive pulmonary dis- 60. Franklin C, Samuel J, Hu T (1994) ventilation in obstructive lung disease. ease: role of expiratory muscles. Am Life-threatening hypotension associ- Clin Chest Med 17:577-590 Rev Respir Dis 148:1037-1042 ated with emergency intubation and 35. Vinegar A, Sinnett EE, Leith DE 48. Marini JJ (1989) Should PEEP be used the initiation of mechanical ventila- (1979) Dynamic mechanisms deter- in airflow obstruction? Am Rev Re- tion. Am J Emerg Med 12:425-428 mine functional residual capacity in spir Dis 140:1-3 61. Keith RL, Pierson DJ (1996) Compli- mice, Mus musculus. J Appl Phy- 49. Ranieri VM, Mascia L, Petruzzelli V, cations of mechanical ventilation: a sio146:867-871 et al (1995) Inspiratory effort and mea- bedside approach. Clin Chest Med 17: 36. Kimball WR, Leith DE, Robins AG surement of dynamic intrinsic PEEP in 439-451 (1982) Dynamic hyperinflation and COPD patients: effects of ventilator 62. Pierson DJ (1994) Barotrauma and ventilator dependence in chronic ob- triggering systems. Intensive Care bronchopleural fistula. In: Tobin MJ structive pulmonary disease. Am Rev Med 21:896-903 (ed) Principles and Practice of Me- Respir Dis 126:991-995 50. Milic-Emili J, Gottfried SB, Rossi A chanical Ventilation. McGraw-Hill, 37. Pepe PE, Marini JJ (1982) Occult posi- (1987) Dynamic hyperinflation: intrin- New York, p 813-836 tive end-expiratory pressure in me- sic PEEP and its ramifications in pa- 63. Pierson DJ (1994) Pneumomediasti- chanically ventilated patients with air- tients with respiratory failure. In: Vin- num. In Murray JF, Nadal JA (eds) flow obstruction. Am Rev Respir cent JL (ed) Update in intensive care Textbook of respiratory medicine. Dis 126:166-170 and emergency medicine: update 2nd edn Saunders, Philadelphia 38. Tobin MJ, Lodato RF (1989) PEER 1987. Springer-Verlag, Berlin, pp pp 2250-2265 auto-PEER and waterfalls. Chest 96: 192-198 64. Pingleton SK (1988) Complications of 449M51 51. Tuxen DV, Lane S (1987) The effects acute respiratory failure. Am Rev Re- 39. Ranieri VM, Grasso S, Fiore T, Giulia- of ventilatory pattern on hyperinfla- spir Dis 137:1463-1493 ni R (1996) Auto-positive end-expiration, airway pressures, and circulation 65. Braman SS, Kaemmerlen JT (1990) tory pressure and dynamic hyperinfla- in mechanical ventilation of patients Intensive care of status asthmaticus. tion. Clin Chest Med 17:379-394 with severe airflow obstruction. Am A 10-year experience. JAMA264: 40. Lodato RE Tobin MJ (1991) Estima- Rev Respir Dis 136:872-879 366-368 tion of auto-PEER Chest 99:520-522 52. Ranieri VM, Eissa NT, Corbeil C, et al 66. Darioli R, Perret C (1984) Mechani- (1991) Effects of positive end-expira- cally controlled hypoventilation in sta- tory pressure on alveolar recruitment tus asthmaticus. Am Rev Respir and gas exchange in patients with the Dis 129:385-387 adult respiratory distress syndrome. Am Rev Respir Dis 144:544-545 910

67. Leatherman JW, Ravenscraft SA, Iber 80. Diot P, Morra L, Smaldone GC (1995) 94. Esteban A, Frutos F, Tobin MJ, et al C, et al (1989) High peak inflation Albuterol delivery in a model of me- (1995) A comparison of four methods does not predict barotrauma during chanical ventilation: comparison of of weaning patients from mechanical mechanical ventilation of status asth- metered-dose inhaler and nebulizer ef- ventilation. N Engl J Med 332:345-350 maticus. Am Rev Respir Dis139: ficiency. Am J Respir Crit Care 95. Pierson DJ (1995) Weaning from me- 154A Med 152:1391-1394 chanical ventilation: Why all the con- 68. Williams TJ, Tuxen DV, Scheinkestel 81. O'Riordan TG, Palmer LB, Smaldone fusion? Respir Care 40:228-232 CD (1992) Risk factors for morbidity GC (1994) Aerosol deposition in me- 96. Ely EW~ Baker AM, Dunagan DR et al in mechanically ventilated patients chanically ventilated patients: optimiz- (1996) Effect on the duration of me- with acute severe asthma. Am Rev Re- ing nebulizer delivery. Am J Respir chanical ventilation of identifying pa- spir Dis 146:607-615 Crit Care Med 149:214-219 tients capable of breathing sponta- 69. Slutsky AS (1993) Mechanical ventila- 82. Dhand R, Jubran A, Tobin MJ (1995) neously. N Engl J Med 335:1864-1869 tion. ACCP Consensus Conference. Bronchodilator delivery by metered- 97. Meduri GU, Abou-Shala N, Fox RC, Chest 104:1833-1857 dose inhaler in ventilator-suported et al (1991) Noninvasive face mask 70. Tobin MJ (1988) Respiratory muscles patients. Am J Respir Crit Care mechanical ventilation in patients in disease. Clin Chest Med 9:263-285 Med 151:1827-1833 with acute hypercapnic respiratory 71. Gottfried SB (1991) The role of PEEP 83. Dhand R, Duarte AG, Jubran A, et al failure. Chest 100:445.454 in the mechanically ventilated COPD (1996) Dose response to bronchodila- 98. Wysocki M, Tric L, Wolff MA, et al patient. In: Marini JJ, Roussos C (eds) tor delivered by metered-dose inhaler (1993) Noninvasive pressure support Ventilatory failure. Springer-Verlag, in ventilator-supported patients. Am ventilation in patients with acute re- Berlin, pp 392-418 Rev Respir Crit Care Med154: spiratory failure. Chest 103:907-913 72. Nava S, Bruschi C, Rubini F, et al 388-393 99. Heffner JE (1989) Medical indications (1995) Respiratory response and in- 84. Hansen-Flaschen J (1997) Neuromus- for tracheotomy. Chest 1:186-190 spiratory effort during pressure sup- cular complications of critical illness. 100. Consensus conference on artificial air- port ventilation in COPD patients. In- Pulm Perspectives (Am Coil Chest ways in patients receiving mechanical tensive Care Med 21:871-873 Phys) 14:1-4 ventilation (1989) Chest 1:178-180 73. Hoffman RA, Ershowsky R Krieger 85. Brochard L, Rauss A, Benito S, et al 101. Marsh HM, Gillespie D J, Baumgart- BP (1989) Determination of auto- (1994) Comparison of three methods ner AE (1989) Timing of tracheostomy PEEP during spontaneous and con- of gradual withdrawal from ventilatory in the critically ill patient. Chest 1: trolled ventilation by monitoring chan- support during weaning from mechan- 190-193 ges in end-expiratory thoracic gas ical ventilation. Am J Respir Crit 102. E1-Naggar M, Sadagopa S~ Levin H~ et volume. Chest 96:613-616 Care Med 150:896-903 al (1976) Factors influencing choice 74. Gay PC, Rodarte JR, Hubmayr RD 86. Esteban A, Alia I, Ibanez J, et al between tracheostomy and prolonged (1989) The effects of positive expira- (1994) Modes of mechanical ventila- translaryngeal intubation in acute re- tory pressure on isovolume flow and tion and weaning. A national survey spiratory failure: a prospective study. dynamic hyperinflation in patients re- of Spanish hospitals. Chest 106: Anesth Analg 55:195-201 ceiving mechanical ventilation. Am 1188-1193 103. Muir JF, Girault C~ Cardinaud JR et al Rev Respir Dis 139:621-626 87. Lessard MR, Brochard LJ (1996) (1994) Survival and long-term follow- 75. Georgopoulos D, Giannouli E, Pata- Weaning from ventilatory support. up of tracheostomized patients with kas D (1993) Effects of extrinsic posi- Clin Chest Med 17:475-489 COPD treated by home mechanical tive end-expiratory pressure on me- 88. Pierson DJ (1995) Non-respiratory as- ventilation. Chest 106:201-209 chanically ventilated patients with pects of weaning from mechanical ven- 104. Menzies R, Gibbons W, Goldberg P chronic obstructive pulmonary disease tilation. Respir Care 40:263-270 (1989) Determinants of weaning and and dynamic hyperinflation. Intensive 89. Marini JJ (1995) Weaning techniques survival among patients with COPD Care Med 19:197-203 and protocols. Respir Care 40: who require mechanical ventilation 76. Scott LR, Benson MS, Pierson DJ 233-238 for acute respiratory failure. Chest 95: (1986) Effect of inspiratory flow rate 90. MacIntyre NR (1995) Respiratory fac- 398-405 and circuit compressible volume on tors in weaning from mechanical venti- 105. Weiss SM, Hudson LD (1994) Out- auto-PEEP during mechanical ventila- latory support. Respir Care 40: come from respiratory failure. Crit tion. Resp~r Care 31:1075-1079 244-248 Care Clin 10:197-215 77. Dhand R, Tobin MJ (1996) Broncho- 91. Pierson DJ (1995) Long-term mechan- 106. Ludwigs UG, Baehrendtz S, Wanecek dilator delivery with metered-dose in- ical ventilation and weaning. Respir M, et al (1991) Mechanical ventilation halers in mechanically ventilated pa- Care 40:289-295 in medical and neurological diseases: tients. Eur Respir J 9:585-595 92. Barrientos-Vega R, Sanchez-Soria 11years of experience. J Intern 78. Crogan SJ, Bishop MJ (1989) Delivery MM, Morales-Garcia C, et al (1997) Med 229:117-124 efficiency of metered-dose aerosols Prolonged sedation of critically ill pa- 107. Seneff MG, Wagner DR Wagner RR et given via endotracheal tubes. Anes- tients with midazolam or propofol: im- al (1995) Hospital and 1-year survival thesiology 70:1008-1010 pact on weaning and costs. Crit Care of patients admitted to intensive care 79. Fink JB, Dhand R, Duarte AG, et al Med 25:33-40 units with acute exacerbations of (1996) Aerosol delivery from a me- 93. Carrasco G, Molina R, Costa J, et al chronic obstructive pulmonary dis- tered-dose inhaler during mechanical (1993) Propofol vs midazolam in ease. JAMA 274:1852-1857 ventilation. Am J Respir Crit Care short-, medium- and long-term seda- 108. Gottlieb LS, Balchum OJ (1973) Med 154:382-387 tion of critically ill patients. A cost Course of chronic obstructive pulmo- benefit analysis. Chest 103:557-564 nary disease following first onset of respiratory failure. Chest 63:5-8