2230 PART 8 Critical Care Medicine

Writing Group for The Alveolar Recruitment for Acute

Respiratory Distress Syndrome Trial (ART) Investigators:

Effect of lung recruitment and titrated positive end-expiratory pressure (PEEP) vs low PEEP on mortality in patients with acute respiratory distress syndrome. JAMA 318:1335, 2017.

■ WEBSITES

ARDS Foundation: www.ardsusa.org

ARDS Support Center for patient-oriented education: www.ards.org

National Health, Lung, and Blood Institute ARDS Clinical Trials information: www.ardsnet.org and www.petalnet.org

Mechanical ventilation refers to devices that deliver positive-pressure

gas, of varying oxygen content, to patients with acute or chronic

respiratory failure. Hypoxemic respiratory failure refractory to supplemental oxygen and requiring mechanical ventilation is most often

due to ventilation-perfusion mismatch or shunt caused by processes

such as pneumonia, pulmonary edema, alveolar hemorrhage, acute

respiratory distress syndrome (ARDS), and sequelae of trauma or

surgery. Hypercapnic respiratory failure is most frequently caused by

severe exacerbations of obstructive lung disease, including asthma and

chronic obstructive pulmonary disease (COPD); loss of central respiratory drive from acute neurologic events, such as stroke, intracranial

hemorrhage, or drug overdose; and respiratory muscle weakness from

diseases such as Guillain-Barré syndrome. Mechanical ventilation may

also be necessary if patients have an artificial airway placed (an endotracheal tube) due to poor airway protection, such as in coma or in the

context of a large upper gastrointestinal hemorrhage and vomiting, or

due to processes leading to large airway obstruction, such as laryngeal

edema. Finally, since mechanical ventilation can lower the work of

breathing compared to spontaneous ventilation, it is a useful adjunct

therapy for shock and multiorgan system failure.

PRINCIPLES OF MECHANICAL

VENTILATION

Although contemporary mechanical ventilators use positive pressure

to inflate the lungs, a patient’s response to pressure applied across the

lung (transpulmonary pressure) depends on the elastic properties of

their lungs and chest wall; the amount of pressure needed to inflate a

lung is the same, therefore, whether applied positively via mechanical

ventilation or negatively using the diaphragm and chest wall muscles.

In ARDS, for example, lungs are “stiff ” or poorly compliant and often

require much more pressure to achieve a physiologic tidal volume

(Fig. 302-1), which, over time, may lead to respiratory muscle fatigue.

If a patient with ARDS is on mechanical ventilation and makes no

spontaneous respiratory effort, using sedation and neuromuscular

blockade, the amount of positive pressure needed to inflate the lung

is equal to the negative inflation pressure required if the patient were

spontaneously breathing; however, the work of breathing is removed

on a ventilator, allowing for sustainable ventilation.

Mechanical ventilation can be lifesaving by restoring adequate oxygenation and correcting hypercapnia. Optimal application of positivepressure ventilation, however, requires avoiding underinflation, which

can cause cycles of alveolar recruitment and then collapse, and at the

other extreme, alveolar overinflation (Fig. 302-2); collectively, these

processes can cause ventilator-induced lung injury by barotrauma and

volume trauma. Optimal tidal volume ventilation occurs along the

lung pressure-volume curve where respiratory system compliance is

302 Mechanical Ventilatory

Support

Scott Schissel

1005 L

2.5 L

0.5 L

90

80

70

60

50

40

30

20

10

–30 –20 –10 0

Pressure (cmH2O)

Volume (liters and % total lung capacity)

10

ARDS

Normal

20 30 40 50

0

FIGURE 302-1 Hypothetical pressure-volume curves of patients with normal lung

function (normal) and acute respiratory distress syndrome (ARDS). A tidal volume

breath of 0.5 L in the normal lung requires 8 cmH2O of pressure (open box), but in

ARDS requires 28 cmH2

O (shaded box).

1005 L

2.5 L

0.5 L

90

80

70

60

50

40

30

20

10

–30 –20 –10 0

Pressure (cmH2O)

Volume (liters and % total lung capacity)

10

ARDS

D.

Alveolar

overdistension

B.

Optimal PEEP:

20 cmH2O

C.

Protective

ventilation

A.

Alveolar

collapse

20 30 40 50

0

FIGURE 302-2 Hypothetical pressure-volume curve of a patients with acute

respiratory distress syndrome (ARDS), demonstrating optimal positive endexpiratory pressure (PEEP) and protective ventilation. A tidal volume breath of

0.5 L initiated at a PEEP of 20 cmH2

O (B), after the area of greatest alveolar collapse

(A). End inhalation occurs within the most compliant portion of the pressure-volume

curve (C) and at a pressure <30 cmH2

O, before the area where lung over distention

occurs (D), minimizing lung injury.

greatest, or where the smallest change in applied pressure leads to the

greatest increase in lung volume (Fig. 302-2, shaded box). To prevent

too low lung volumes at end exhalation, where alveolar collapse occurs,

the ventilator can be set to maintain a specified positive pressure at end

exhalation, or positive end-expiratory pressure (PEEP) (Fig. 302-2, B.

Optimal PEEP). Lower tidal volume ventilation (goal 6 mL/kg of ideal

body weight) can help prevent the end-inhalation, or “plateau,” pressure (measured just after flow stops at end inhalation) from exceeding 30 cmH2

O; this approach minimizes barotrauma- and volume

trauma–induced lung injury, especially in ARDS patients (Fig. 302-2,

C. Protective ventilation).

2231 Mechanical Ventilatory Support CHAPTER 302

mode where tidal volume is set at x. Importantly, since lung compliance

can change dynamically, tidal volume may also change with PCV; tidal

volume and minute ventilation, therefore, must be monitored since

there is no assurance of delivered ventilation volumes as with volume

control. PCV is often used to limit peak airway and lung distending

(plateau) pressures in situations where high pressure can cause harm,

such as in ARDS or after thoracic surgery with fresh suture lines in the

airways or lung parenchyma. Importantly, however, inspiratory flow

rate and volume are dependent variables in PCV, unlike in volume

control ventilation, and not set by the clinician. Spontaneously breathing patients on PCV can generate a relative negative pressure in the

ventilator circuit, transiently decreasing the positive pressure below the

set point; the ventilator responds by increasing gas flow until it restores

the set pressure, resulting in higher inspiratory flow rates, a higher

tidal volume for that breath, and importantly, increased pressure across

the alveoli, equal to the absolute (negative) pressure generated by the

patient plus the positive pressure set by the clinician (Fig. 302-3).

Since mechanical ventilators do not routinely measure or graphically

display the negative pressure generated by the patient, clinicians can be

unaware of this additional transalveolar pressure and potential harm

by volume and barotrauma; importantly, therefore, clinicians should

monitor for increases in tidal volume on PCV.

■ PRESSURE-REGULATED VOLUME CONTROL

VENTILATION

Advances in ventilator technology, such as flow and pressure sensors and

microprocessors, allow for new modes of mechanical ventilation that

meld the benefits of volume and pressure control ventilation. Pressureregulated volume control ventilation (PRVC) is a fully supported mode

of ventilation where the clinician sets a target tidal volume, as in volume control ventilation, but it allows a patient to make spontaneous

respiratory efforts and vary inspiratory flow rates, as in PCV, enhancing patient comfort and ventilator synchrony. PRVC senses patient

inspiratory efforts and delivers the least amount of positive pressure

to achieve the targeted tidal volume; since patient efforts can vary and

ventilator adaptation is not instantaneous, tidal volumes can vary from

breath to breath on PRVC. In disease states where tidal volume needs

tight control to prevent volume trauma, such as in ARDS, PRVC must

be used cautiously if the patient can make significant respiratory effort.

■ PRESSURE SUPPORT VENTILATION

Pressure support ventilation (PSV) and PCV are very similar except

there is no mandated ventilation, or set mechanical respiratory rate,

MECHANICAL VENTILATION MODES

Mechanical ventilation entails controlling or monitoring the same

basic variables involved in spontaneous, negative-pressure breathing,

including respiratory rate, tidal volume (VT), inspiratory flow rate and

time, and the fraction of inspired oxygen (Fio2

). In addition, PEEP is

a variable specific to positive-pressure ventilation and set by the clinician. The mechanical ventilation mode determines how much control

the clinician and ventilator have over these variables versus the patient;

for example, assist control (AC) mode allows for essentially complete

operator control of all variables, whereas pressure support (PS) permits

the patient to control important variables, such as respiratory rate, VT

,

and flow rates (Table 302-1).

■ ASSIST CONTROL VENTILATION

AC allows the clinician to control nearly all ventilator variables and

is widely used when patients cannot safely participate in their own

ventilatory efforts, such as when deeply sedated or unstable from acute

respiratory failure or other critical illness. Most AC ventilation is in volume control mode where the operator sets a specific VT and respiratory

rate, thereby assuring a minimum minute ventilation (VE

). In addition

to the set rate, patients can get additional, fully supported breaths at

the set VT by making an inspiratory effort, which is sensed by the ventilator and triggers the breath. The inspiratory flow rate is set by the

operator; thus, a dyspneic patient may meet resistance on inhalation

if their desired flow rate is higher than the set rate, possibly leading to

patient distress and increased work of breathing. In AC volume mode,

the operator also sets the PEEP and Fio2

. Importantly, since VT is an

independent variable in volume control (i.e., set by the clinician), the

end-inhalation (or plateau) pressure is a dependent variable not controlled by the clinician but rather determined by the compliance of the

lung. Inspiratory pressures must be monitored, therefore, to minimize

barotrauma.

Although AC is often volume controlled, it can be used in a pressure

control mode, also referred to as pressure control ventilation (PCV).

The key difference between volume control and PCV is that an inspiratory (or “driving”) pressure is set instead of a tidal volume in PCV;

thus, every time the ventilator delivers a breath, it raises the airway

pressure to the set amount above PEEP until inspiratory flow decreases

below a set threshold, therefore ending inhalation. Thus, the resulting

tidal volume will vary depending on the compliance of the lung. In a

sedated and paralyzed patient (making no respiratory effort), the pressure required to generate a specific tidal volume (x) using PCV should,

in the same patient, be equal to the plateau pressure in volume control

TABLE 302-1 Key Features of Commonly Used Mechanical Ventilation Modes

MODE

VARIABLES SET BY CLINICIAN

(INDEPENDENT)

MONITORED VARIABLES

(DEPENDENT) ADVANTAGES DISADVANTAGES

Assist control–volume

control

VT

Respiratory rate

PEEP

Fio2

Inspiratory flow rate

Peak inspiratory airway

pressure

End-inhalation (plateau)

pressure

VE

Guarantee minimum VT

 and VE

Control VT

, limiting volume trauma

Barotrauma from high plateau pressure

Patient-ventilator dyssynchrony,

increased work of breathing

Assist control–

pressure control

Inspiratory driving pressure

Respiratory rate

PEEP

Fio2

Tidal volume

VE

Limit barotrauma (if patient

respiratory efforts minimal)

Inspiratory flow can vary with

patient effort (improved comfort/

synchrony)

Vt

 and VE

 not mandated; must

monitor closely

Patient’s respiratory effort can lead to

large VT

 and volume trauma

Pressure-regulated

volume control

VT

Respiratory rate

PEEP

Fio2

Peak inspiratory airway

pressure

End-inhalation (plateau)

pressure

VE

Patient effort can vary inspiratory

flow, increasing comfort, and

ventilator synchrony

Guarantee minimum VT

 and VE

Variable patient effort can lead to VT

larger than set VT

; monitor to prevent

volume trauma

Pressure support Inspiratory pressure

PEEP

Fio2

VT

Respiratory rate

VE

Patient effort preserved and

controls VT

, inspiratory flow, and

respiratory rate, allowing for

ventilator synchrony

Apnea and hypoventilation possible;

must monitor respiratory rate, VT

, and VE

closely

Abbreviations: Fio2

, fraction of inspired oxygen; PEEP, positive end-expiratory pressure; VE

, minute ventilation; VT

, tidal volume.

2232 PART 8 Critical Care Medicine

1005 L

2.5 L

0.5 L

90

80

70

60

50

40

30

20

10

–30 –20 –10 0

Pressure (cmH2O)

Volume (liters and % total lung capacity)

10 20 30 40 50

0

A

B

FIGURE 302-3 Hypothetical pressure-volume curve of a patient on pressure control

ventilation, paralyzed (A) and breathing spontaneously (B). A. Paralyzed patient

(light shaded box): positive end-expiratory pressure (PEEP), 10 cmH2

O; inspiratory

(driving) pressure: 15 cmH2

O; end-inhalation (plateau) pressure, 25 cmH2

O; tidal

volume (VT

), 300 mL. B. Breathing patient (dark shaded box): PEEP, 10 cmH2

O;

inspiratory (driving) pressure, 15 cmH2

O; patient effort (negative “pulling” pressure),

10 cmH2

O; end-inhalation (plateau) pressure displayed on ventilator, 25 cmH2

O; net

end-inhalation (transalveolar) pressure, 35 cmH2

O; VT

, 700 mL.

TABLE 302-2 Common Contraindications to Noninvasive Ventilation

Inability to protect the airway, such as severe encephalopathy

High risk for aspiration, such as vomiting or severe upper gastrointestinal

bleeding

Difficulty clearing respiratory secretions

Facial trauma or surgery

Upper airway obstruction or compromise

Significant hemodynamic instability

on PSV, and ventilator support is entirely patient triggered and controlled. The clinician sets the Fio2

, PEEP, and maximum inspiratory

pressure. When patients make a negative-pressure inspiratory effort on

PSV, the ventilator senses this pressure change and increases positive

pressure to the set inspiratory pressure level, maintaining it until flow

decreases below a set threshold (often ~20% of peak inspiratory flow);

at this point, inhalation ends and pressure drops back to the set PEEP.

The tidal volume on PSV is monitored but not assured, is determined

by lung compliance, and depends on the patient’s sustaining an inspiratory effort. Tidal volume, minute ventilation, and respiratory rate,

therefore, must be closely monitored on PSV to detect hypopnea/apnea

and hypoventilation. PSV is often used when patients are less sedated

and able to participate in respiratory work, such as when transitioning

off mechanical ventilation or on a ventilator only for airway support.

■ NONINVASIVE POSITIVE-PRESSURE

VENTILATION

Noninvasive ventilation (NIV) is historically referred to as positivepressure ventilation and is delivered via a nasal or full-face mask at a

continuous pressure (continuous positive airway pressure [CPAP]) or

at different inspiratory and expiratory pressures (bilevel positive airway

pressure [BiPAP]). Most current noninvasive ventilators, however, can

function in full support modes, including volume control ventilation.

NIV is particularly beneficial for acute respiratory failure where the

underlying cause responds quickly to treatment, minimizing the need

for prolonged mechanical ventilatory support. For example, in moderate acute hypercarbia (blood pH between 7.25 and 7.35) due to exacerbations of COPD, NIV reduces the need for endotracheal intubation

and shortens hospital length of stay; more severe acute respiratory

acidosis from COPD exacerbations (blood pH <7.2) generally requires

mechanical ventilation with an endotracheal tube. NIV can also be an

important adjunct treatment for respiratory failure from acute cardiogenic pulmonary edema, where interventions, such as diuresis and

vasodilator therapy, can rapidly improve gas exchange and respiratory

mechanics. NIV, particularly with volume support modes, is effective

in managing chronic respiratory failure from restrictive lung diseases,

such as severe scoliosis and respiratory muscle weakness, and in COPD

complicated by chronic hypercapnia, where nocturnal NIV reduces

COPD-related hospital admissions. Despite the technical innovations

in NIV and expanding clinical applications, several important contraindications to using mechanical ventilation without a secure airway,

such as an endotracheal tube or tracheostomy tube, include delirium,

difficulty managing respiratory secretions, and hemodynamic instability (Table 302-2).

STRATEGIES TO OPTIMIZE GAS EXCHANGE

ON MECHANICAL VENTILATION

■ ARTERIAL OXYGENATION

The optimal partial pressure of arterial oxygen (Pao2

) and oxygen

saturation measured by pulse oximetry (SpO2

) during mechanical

ventilation remain uncertain. Although tissue hyperoxia can cause

oxidative injury, with some clinical studies of mechanically ventilated

patients suggesting worse clinical outcomes with higher Fio2

 and when

Pao2

 frequently reaches supraphysiologic levels, randomized studies

comparing conservative oxygen delivery to a more liberal oxygen strategy have not demonstrated a clear advantage to conservative oxygen

delivery. In ARDS, targeting a lower Pao2

 of 55–70 mmHg (or SpO2

 of

88–92%) versus a higher, but more physiologic, Pao2

 of 90–105 mmHg

(or SpO2

 >96%) did not lower mortality, with adverse events being

more frequent in the lower Pao2

 group, including mesenteric ischemia.

Pao2

 and SpO2

 targets, therefore, should be individualized to patients

considering circumstances where even mild hyperoxia may be harmful, such as in recovery from ischemic brain injury and, conversely,

where lower Pao2

 levels (<55–70 mmHg) may be less optimal, such as

in patients with ARDS and evidence of bowel dysfunction. Regardless

of the approach, there is no evidence that a supraphysiologic Pao2

(>100 mmHg) has clinical benefit; thus, sustained hyperoxia should

be avoided.

Arterial hypoxemia refractory to standard mechanical ventilation

techniques is common in severe acute lung disease, especially ARDS.

In general, if the Fio2

 requirement is >0.6 or the Pao2

:Fio2

 ratio is <150

mmHg, additional interventions should be considered to improve

arterial oxygenation. The application of adequate PEEP to prevent

alveolar collapse during exhalation improves oxygenation by decreasing V.

/Q

.

mismatch and shunt in areas of atelectatic lung. PEEP should

ideally be set at the lower inflection point of the most compliant region

of the lung pressure-volume curve (Fig. 302-2B). Although optimal

PEEP may improve arterial oxygenation, achieving best PEEP has

not been shown to improve clinical outcomes definitively and may

have deleterious effects, including barotrauma with pneumothorax

and hypotension from decreasing venous return to the right ventricle.

Patients with refractory hypoxemia are often dyspneic on mechanical

ventilation and make significant respiratory efforts dyssynchronous

with the ventilator despite deep sedation, leading to poor ventilation

and preventing optimal V.

/Q

.

 matching. In this context, neuromuscular

blockade can be very effective at restoring effective mechanical ventilation and optimizing gas exchange. Although a necessary intervention

at times, neuromuscular blockade does not improve overall outcomes

in ARDS, can contribute to critical illness myopathy, and requires adequately deep sedation to prevent conscious paralysis; thus, it should

be used only when necessary to treat refractory hypoxemia. In ARDS,

diseased lung is predominantly dependent, and placing the patient in a

prone position for extended periods can significantly improve arterial

2233 Mechanical Ventilatory Support CHAPTER 302

oxygenation. The role of prone positioning in other disease states is

unknown and can be associated with adverse events unless performed

by a trained team, such as dislodging endotracheal tubes and central

venous catheters. Delivery of pulmonary vasodilator medications

through the airway can improve perfusion to ventilated alveolar units,

therefore improving V.

/Q

.

matching and arterial oxygenation. Inhaled

prostacyclins, such as epoprostenol, and nitric oxide are commonly

used to treat refractory hypoxemia and can increase, on average,

the Pao2

:Fio2

 ratio by 20–30 mmHg. Hypoxemia refractory to these

multiple interventions may require consideration of transitioning to

extracorporeal membrane oxygenation (ECMO), see below.

■ HYPERCAPNIA

Except for rare circumstances of excess carbon dioxide (CO2

) production (Vco2

), which can occur in the setting of fever, sepsis, overfeeding,

and thyrotoxicosis, most hypercapnia is due to inadequate alveolar

ventilation (VA) from an increase in the fraction of dead space (VD)

(the volume of each breath not participating in CO2

 exchange) relative

to the total minute ventilation (VE

), expressed as VA = VE

 (1 – VD/VT).

Normal physiologic dead space is ~150 mL (~2 mL/kg), making the

VD/VT for a 500-mL tidal volume breath 0.3. In acute respiratory failure

due to ARDS, for example, VD may increase due to poorly perfused

but ventilated portions of lung, while ventilation strategies lead to low

VT; thus, a modest increase in VD to 200 mL and a low VT of 300 mL

will result in a VD/VT of 0.66, a situation where hypercapnia may easily

develop. Hypercapnia in the context of low tidal volume (6 mL/kg)

ventilation for ARDS often causes acute respiratory acidosis that can

be managed with higher respiratory rates, up to 30 breaths/min. Respiratory acidosis is often tolerated down to a pH of 7.2, so-called “permissive hypercapnia,” but progressive acidosis may require intravenous

alkalinizing therapy (e.g., sodium bicarbonate or tromethamine) or

accepting an increase in VT

. In severe exacerbations of obstructive lung

disease, COPD, and status asthmaticus, hypercapnia and acute respiratory acidosis are common despite mechanical ventilation, with average

Paco2

 values of 65 mmHg and blood pH of 7.20 after initial endotracheal intubation. Poor alveolar ventilation is primarily due to dead

space created by alveolar capillary compression in areas of alveolar

overdistension and lung hyperinflation. Increasing minute ventilation

by increasing the respiratory rate or tidal volume will, therefore, often

paradoxically worsen hypercapnia by increasing gas trapping and VD/

VT

. The optimal ventilator strategy for severe obstructive lung disease

physiology entails using lower respiratory rates, usually 9–12 breaths/

min, and moderate tidal volumes (7–9 mL/kg) to maintain a minute

ventilation of ~10 L/min; higher minute ventilation usually worsens

hyperinflation and can cause barotrauma. To prevent dyspneic patients

from driving hyperventilation, deeper sedation and occasionally neuromuscular blockade are necessary until severe bronchial obstruction

responds to medical therapy. Although permissive hypercapnia can

minimize barotrauma and volume trauma during mechanical ventilation, hypercapnia has adverse effects including increased intracranial

pressure, pulmonary artery vasoconstriction, and even depressed

cardiac contractility (Table 302-3). The benefits and risks of a hypercapnia ventilatory strategy must, therefore, account for the individual

patient’s comorbid medical conditions, for example, acute neurologic

injury and risk of critical increases in intracranial pressure.

COMPLICATIONS OF MECHANICAL

VENTILATION

■ AIRWAY

Endotracheal intubation and mechanical ventilation can lead to several

pulmonary and extrathoracic complications, especially when patients

remain on mechanical ventilation for >7 days. Upper airway complications from endotracheal tube placement include vocal cord trauma

(edema, avulsion, paralysis), tracheal stricture due to granulation tissue, and tracheomalacia. Vocal cord injury can lead to postextubation

stridor (PES) and need for replacement of an endotracheal tube. PES

risk factors include prolonged (>7 days) or traumatic intubation, large

endotracheal tube size, previous episode of PES, and head/neck surgery or trauma. Patients with PES risk factors should have the balloon

cuff deflated on their endotracheal tube and should be assessed for air

passing across the balloon (so-called “cuff leak test”). Patients with no

cuff leak have an approximate 30% risk of PES and may need further

assessment for causes of PES, with endotracheal tube removal delayed

until the underlying process is treated.

■ ADVERSE CARDIOPULMONARY EFFECTS OF

POSITIVE-PRESSURE VENTILATION

High positive intrathoracic pressure, such as sustained inspiratory

plateau pressures >30 cmH2

O or high PEEP, can cause several manifestations of lung barotrauma, including worsening of acute lung injury,

pneumomediastinum, pneumothorax, and even pneumoperitoneum.

Although positive-pressure ventilation can improve left-sided heart

failure by decreasing left ventricular preload and afterload, right ventricular failure and pulmonary arterial hypertension can worsen due to

inadequate right ventricular preload and an increase in right ventricular afterload and pulmonary vascular resistance; these effects on the

right ventricle and pulmonary circulation should be considered when

choosing a ventilatory strategy in patients with severe right-sided heart

disease. In addition, blunted central venous return can cause upper and

lower extremity edema, especially in the setting of aggressive IV fluid

resuscitation and vascular leak related to the underlying critical illness.

■ VENTILATOR-ASSOCIATED PNEUMONIA

Several factors during mechanical ventilation, such as violation of

natural airway defenses, sedation with depressed cough, and microaspiration, increase the risk of bacterial entry into the lower respiratory

tract and development of pneumonia. Ventilator-associated pneumonia (VAP) occurs in up to 15% of mechanically ventilated patients and

causes death in nearly 50% of patients. VAP is a lower respiratory tract

infection that occurs ≥48 h after initiating mechanical ventilation and

requires the following: (1) new pulmonary opacities on chest x-ray,

(2) a clinical change consistent with pneumonia (fever, increased sputum, leukocytosis, or increase in ventilator support, such as increased

Fio2

 or PEEP), and (3) positive microbial culture obtained from the

lower respiratory tract via deep endotracheal suctioning or bronchoscopy specimen (bronchoalveolar lavage or protected endobronchial

brushing). Most VAP pathogens are typical hospital-acquired bacteria including Staphylococcal aureus, Pseudomonas aeruginosa, and

several other enteric gram-negative rods. In cases of suspected VAP,

early empiric antibiotic therapy generally requires an intravenous

β-lactam with broad gram-negative rod activity, such as piperacillintazobactam, cefepime, or ceftazidime. Empiric therapy with vancomycin or linezolid for methicillin-resistant S. aureus (MRSA) or with a

carbapenem for multidrug-resistant enteric gram-negative rods should

depend on local intensive care unit (ICU) infection control data or

individual patient risk for these resistant bacteria. If possible, based on

respiratory cultures, empiric antibiotic regimens should be narrowed

and total treatment duration should be 7 days. Given the significant

morbidity and mortality for VAP, prevention strategies are paramount

and should be part of standardized care or “bundles.” VAP prevention

interventions supported by clinical trial evidence include head-of-bed

elevation to at least 30–45° (70% VAP reduction compared to supine

position), specialized endotracheal tube use with a suction port above

TABLE 302-3 Adverse Effects of Hypercapniaa

Pulmonary arterial vasoconstriction (possible worsening of right heart failure)

Rightward shift of the oxyhemoglobin curve

Cerebral vasodilation

Increased intracranial pressure

Sympathetic-adrenal stimulation

Reduced cardiac contractility (especially in the presence of β-adrenergic

blocking therapy)

a

Some effects decrease if cellular pH is corrected.

2234 PART 8 Critical Care Medicine

• Age >65

• Congestive heart failure

• COPD

• APACHE-II score >12

• BMI >30

• Significant secretions

• >2 medical comorbidities

• >7 days on mechanical

 ventilation

• Underlying process improved

• Awake, minimal sedation

• FIO2, <0.5, PEEP <8 cmH2O

• SaO2 >88%

• Stable hemodynamics

• Minimal secretions/good cough

*High-risk for respiratory failure

No

No

No

Yes

Yes

Yes

Yes

Continue

mechanical

ventilation

Failure/

reintubation

High-flow O2

or NIV

Stable/improved

respiratory

status? SUCCESS

(off mechanical

ventilation)

Extubation

Recurrent respiratory

failure or high risk*?

Spontaneous

breathing trial

Passed?

Daily assessment

Ready to extubate?

FIGURE 302-4 Algorithm for discontinuing mechanical ventilation. APACHE-II, Acute Physiology and Chronic Health Enquiry II; BMI, body mass index; COPD, chronic

obstructive pulmonary disease; PEEP, positive end-expiratory pressure; NIV, noninvasive ventilation.

the cuff to minimize aspirated secretions (50% VAP reduction), minimization of ventilator circuit tubing changes (prevents bacterial entry),

and hand hygiene before handling the ventilatory circuit. Practices

with uncertain value in reducing VAP but that are still reasonable

include limiting deep tracheal suctioning, daily sedation interruption,

and routine mouth and dental care.

■ OTHER

The systemic physiologic stress associated with mechanical ventilation

and necessary adjunctive therapies, such as sedation and neuromuscular blockade, can cause significant extrathoracic complications. The

more common disorders include gastrointestinal stress ulcers and

bleeding, deep venous thrombosis and pulmonary embolism, sleep

disruption and delirium, and critical illness–associated myopathy,

sometimes leading to prolonged mechanical ventilation. To minimize

the risk of these adverse events, ICUs should institute care bundles

including daily interruption of sedatives and assessment for extubation

and prophylaxis for deep venous thrombosis.

LIBERATION FROM MECHANICAL

VENTILATION

Discontinuing mechanical ventilation and transitioning a patient back

to spontaneous breathing is often referred to as ventilator “weaning,”

implying dependency on positive-pressure ventilation once started.

Although patients on prolonged mechanical ventilation can develop

respiratory muscle weakness, this occurs is a minority of patients.

Approaching removal of ventilator support as a “wean” extends unnecessary mechanical ventilation time up to 40%. Liberating a patient from

mechanical ventilation, therefore, should be more active by frequently

assessing a patient’s readiness for spontaneous breathing, determined

largely by resolution of the underlying process causing respiratory

failure (Fig. 302-4). Important criteria indicating a patient may be

ready for extubation include the following: underlying disease process

has improved, patient is awake and largely off sedative medications,

Fio2

 ≤0.5, PEEP <8 cmH2

O, SaO2

 >88%, stable hemodynamics, and

manageable respiratory secretions with adequate cough. These criteria

should be assessed daily, and if achieved, patients should have a spontaneous breathing trial (SBT)—a maneuver wherein positive pressure

is set to a minimum to compensate for endotracheal tube resistance

(usually 5–7 cmH2

O) and the patient breathes spontaneously from

30–120 min. A patient “passes” the SBT if they appear comfortable

overall (no marked anxiety or diaphoresis) and have a respiratory rate

<35, SaO2

 >90%, systolic blood pressure between 90 and 180 mmHg,

and heart rate change of <20%. Patients passing an SBT have a >70%

chance of successful extubation. Incorporating extubation “readiness”

screening followed by SBT into a care protocol leads to 25% fewer

ventilator days and a 10% decrease in ICU length of stay compared to

traditional ventilator weaning.

Although many physiologic variables correlate with successful

liberation from mechanical ventilation, such as minute ventilation,

negative inspiratory force generation, and the respiratory rate–to–tidal

volume ratio (Tobin index), overrelying on these measures versus the

outcome of an SBT leads to unnecessary delays in extubation. Risk

factors for failing extubation even after a successful SBT include age

>65, congestive heart failure, COPD, Acute Physiology and Chronic

Health Enquiry (APACHE-II) score >12, body mass index (BMI)

>30, significant secretions, >2 medical comorbidities, and >7 days on

mechanical ventilation. Patients with these risk factors transitioned

immediately after extubation to noninvasive respiratory support using

either high-flow oxygen or positive-pressure NIV have significantly

lower rates of reintubation and need to resume mechanical ventilation.

Although NIV is indicated for patients with hypercapnia after extubation, high-flow oxygen support for all other patients may be preferable

given similar efficacy to NIV in preventing reintubation and generally

better patient comfort. Although many factors can cause a patient to

fail an SBT or require reintubation and continued mechanical ventilation, common processes perpetuating mechanical ventilation include

critical illness myopathy and polyneuropathy, myocardial ischemia,

congestive heart failure, vascular and extravascular volume overload,

delirium, malnutrition, and electrolyte abnormalities (hypophosphatemia, hypokalemia, and hypomagnesemia). These processes should

be evaluated and treated, as necessary, in patients failing attempts to

discontinue mechanical ventilation.

EXTRACORPOREAL GAS EXCHANGE

Despite interventions to optimize oxygenation and alveolar ventilation on mechanical ventilation, some patients suffer life-threatening

hypoxemia, refractory respiratory acidosis, and barotrauma and may

be candidates for salvage therapy with extracorporeal gas exchange—a

procedure whereby blood continuously circulates outside the body

through a device that oxygenates it, removes CO2

, and then returns

blood to the patient’s circulation. Although often referred to as

ECMO, modern gas exchange membranes both deliver oxygen and

remove CO2

, replacing the gas exchange function of the lung. The

main components of an ECMO “circuit” include vascular cannulas to

remove and return blood to the patient, a pump to circulate blood,

and a gas exchange membrane. ECMO can provide varying levels of

2235Approach to the Patient with Shock CHAPTER 303

TABLE 302-4 Main Types and Key Features of Extracorporeal Gas Exchange

TERM DESCRIPTION KEY FEATURES IMPORTANT TECHNICAL NOTES

VA-ECMO (venoarterial

extracorporeal membrane

oxygenation)

Deoxygenated blood drains via venous catheter to

a pump and membrane oxygenator; blood is then

returned to the arterial system

Circulatory and respiratory

support

Requires large vascular catheters (16–30 Fr)

Higher blood flow rates (2–6 L/min)

VV-ECMO

(venovenous-ECMO)

Deoxygenated blood drains via venous catheter to

a pump and membrane oxygenator; blood is then

returned to the venous system

Respiratory support Requires large vascular catheters (20–30 Fr)

Higher blood flow rates (2–5 L/min)

ECCO2

R (extracorporeal CO2

removal)

Venous catheter drains blood to a CO2

 removal

device; blood then returns via a venous catheter

Partial respiratory support, CO2

removal only

Requires smaller vascular catheters (14–18 Fr)

Lower blood flow rates (0.25–2 L/min)

both respiratory and circulatory support depending on the clinical

situation (Table 302-4). In a patient both in shock and requiring full

respiratory support, the ECMO circuit would include a central venous

cannula (V) to remove blood and a central arterial cannula (A) to

return oxygenated blood at relatively high flow rates (up to 6 L/min),

providing mechanical circulatory support, so-called VA-ECMO. In

the absence of shock, both the draining and return vascular cannulas

can be central venous, or VV-ECMO, but blood flow is still relatively

high (2–5 L/min) to provide adequate oxygen delivery to tissues. In

situations where a patient’s lungs can provide adequate oxygenation but

insufficient CO2

 removal, such as severe obstructive lung disease exacerbations, a venovenous circuit with low blood flows (0.25–2 L/min) is

often adequate to remove CO2

 and treat refractory respiratory acidosis,

a process called extracorporeal CO2

 removal (ECCO2

R).

Although technologic advances in the ECMO pumps, gas exchange

membranes, and even vascular catheters have reduced ECMO-related

complications, the procedure is resource-intensive and still associated

with several adverse events, including cannula site hemorrhage and

vascular injury, catheter-related infection, pneumothorax, pulmonary

and gastrointestinal hemorrhage, limb ischemia, intracranial hemorrhage, and disseminated intravascular coagulation. Moreover, despite

some promising clinical outcomes data, the mortality benefit from

ECMO, especially in ARDS, remains unclear. Selecting patients most

likely to benefit from ECMO, therefore, is very important, and in addition to exhausting traditional mechanical ventilatory support, patients

being considered for ECMO should have a reversible underlying illness

or be eligible for organ transplant (heart and/or lung), have no chronic

severe end-organ disease (e.g., severe kidney disease), have no contraindication to systemic anticoagulation, have a good functional status

before the acute illness requiring ECMO, and have a good neurologic

prognosis.

■ FURTHER READING

Acute Respiratory Distress Syndrome Network et al: Ventilation

with lower tidal volumes as compared with traditional tidal volumes

for acute lung injury and the acute respiratory distress syndrome. N

Engl J Med 342:1301, 2000.

Barrot L et al: Liberal or conservative oxygen therapy for acute respiratory distress syndrome. N Engl J Med 328:999, 2020.

Girard T et al: An official American Thoracic Society clinical practice

guideline: Liberation from mechanical ventilation in critically ill

adults. Rehabilitation protocols, ventilator liberation protocols, and

cuff leak tests. Am J Respir Crit Care Med 195:120, 2017.

Hernandez G et al: Effect of post extubation high-flow nasal cannula

vs non-invasive ventilation on reintubation and post extubation

respiratory failure in high risk patients. A randomized clinical trial.

JAMA 316:1565, 2016.

Moss M et al: Early neuromuscular blockade in the acute respiratory

distress syndrome. N Engl J Med 380:1997, 2019.

Murphy PB et al: Effect of home noninvasive ventilation with oxygen

therapy vs oxygen therapy alone on hospital readmission or death

after an acute COPD exacerbation. A randomized clinical trial.

JAMA 317:2177, 2017.

Tramm R et al: Extracorporeal membrane oxygenation for critically ill

adults. Cochrane Database Syst Rev 1:CD010381, 2015.

Shock is the clinical condition of organ dysfunction resulting from

an imbalance between cellular oxygen supply and demand. This

life-threatening condition is common in the intensive care unit (ICU).

A multitude of heterogeneous disease processes can lead to shock. The

organ dysfunction seen in early shock is reversible with restoration of

adequate oxygen supply. Left untreated, shock transitions from this

reversible phase to an irreversible phase and death from multisystem

organ dysfunction (MSOF). The clinician is required to identify the

patient with shock promptly, make a preliminary assessment of the

type of shock present, and initiate therapy to prevent irreversible organ

dysfunction and death. In this chapter, we review a commonly used

classification system that organizes shock into four major types based

on the underlying physiologic derangement. We discuss the initial

assessment utilizing the history, physical examination, and initial diagnostic testing to confirm the presence of shock and determine the type

of shock causing the organ dysfunction. Finally, we will discuss key

principles of initial therapy with the aim of reducing the high morbidity and mortality associated with shock.

■ PATHOPHYSIOLOGY OF SHOCK

The cellular oxygen imbalance of shock is most commonly related to

impaired oxygen delivery in the setting of circulatory failure. Shock

can also develop during states of increased oxygen consumption or

impaired oxygen utilization. An example of impaired oxygen utilization is cyanide poisoning, which causes uncoupling of oxidative phosphorylation. This chapter will focus on the approach to the patient with

shock related to inadequate oxygen delivery.

In the setting of insufficient oxygen supply, the cell is no longer able

to support aerobic metabolism. With adequate oxygen, the cell metabolizes glucose to pyruvate, which then enters the mitochondria where

ATP is generated via oxidative phosphorylation. Without sufficient

oxygen supply, the cell is forced into anaerobic metabolism, in which

pyruvate is metabolized to lactate with much less ATP generation (per

mole of glucose). Maintenance of the homeostatic environment of the

cell is dependent on an adequate supply of ATP. ATP-dependent ion

pumping systems, such as the Na+/K+ ATPase, consume 20–80% of the

cell’s energy. Inadequate oxygen delivery and subsequent decreased ATP

disrupt the cell’s ability to maintain osmotic, ionic, and intracellular

pH homeostasis. Influx of calcium can lead to activation of calciumdependent phospholipases and proteases, causing cellular swelling

and death. In addition to direct cell death, cellular hypoxia can cause

damage at the organ system level via leakage of the intracellular contents into the extracellular space activating inflammatory cascades and

altering the microvascular circulation.

Section 2 Shock and Cardiac Arrest

303 Approach to the Patient

with Shock

Anthony F. Massaro