positive pressure ventilation in the cardiac intensive ... · including noninvasive positive...

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J O U R N A L O F T H E A M E R I C A N C O L L E G E O F C A R D I O L O G Y V O L . 7 2 , N O . 1 3 , 2 0 1 8

ª 2 0 1 8 T H E A M E R I C A N C O L L E G E O F C A R D I O L O G Y F O U N D A T I O N .

P U B L I S H E D B Y E L S E V I E R . A L L R I G H T S R E S E R V E D .

THE PRESENT AND FUTURE

COUNCIL PERSPECTIVES

Positive Pressure Ventilationin the Cardiac Intensive Care Unit
Carlos L. Alviar, MD,a,* P. Elliott Miller, MD,b,c,* Dorothea McAreavey, MD,c Jason N. Katz, MD, MHS,d
Burton Lee, MD,e Brad Moriyama, PHARMD,c Jeffrey Soble, MD,f Sean van Diepen, MD, MSC,g

Michael A. Solomon, MD,c,h,y David A. Morrow, MD, MPH,i,y for the ACC Critical Care Cardiology Working Group

ABSTRACT

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Contemporary cardiac intensive care units (CICUs) provide care for an aging and increasingly complex patient population.

The medical complexity of this population is partly driven by an increased proportion of patients with respiratory failure

needing noninvasive or invasive positive pressure ventilation (PPV). PPV often plays an important role in the management

of patients with cardiogenic pulmonary edema, cardiogenic shock, or cardiac arrest, and those undergoing mechanical

circulatory support. Noninvasive PPV, when appropriately applied to selected patients, may reduce the need for invasive

mechanical PPV and improve survival. Invasive PPV can be lifesaving, but has both favorable and unfavorable interactions

with left and right ventricular physiology and carries a risk of complications that influence CICU mortality. Effective

implementation of PPV requires an understanding of the underlying cardiac and pulmonary pathophysiology. Cardiolo-

gists who practice in the CICU should be proficient with the indications, appropriate selection, potential cardiopulmonary

interactions, and complications of PPV. (J Am Coll Cardiol 2018;72:1532–53) © 2018 the American College of Cardiology

Foundation. Published by Elsevier. All rights reserved.

T he advanced cardiac intensive care unit(CICU) has evolved from a unit focused onarrhythmia monitoring and acute coronary

interventions to a high-complexity environment car-ing for patients with cardiovascular diseases withmultisystem organ dysfunction and severe noncar-diac comorbidities (1,2). Previously common reasonsfor CICU admission, including acute myocardialinfarction (MI), have diminished in their contribu-tion, whereas noncardiac primary diagnoses, such assepsis, acute renal failure, and respiratory failure,have increased (3). An analysis of Medicare data

N 0735-1097/$36.00

e views expressed in this paper by the American College of Cardiology’s (

t necessarily reflect the views of the Journal of the American College of

m the aDivision of Cardiovascular Medicine, University of Florida Colleg

vascular Medicine, Yale University School of Medicine, New Haven, Conn

alth Clinical Center, Bethesda, Maryland; dDivisions of Cardiology and P

rth Carolina, Center for Heart and Vascular Care Chapel Hill, Chapel Hill,

itical Care Medicine, University of Pittsburgh School of Medicine, Pittsbur

e, Rush University Medical Center, Chicago, Illinois; gDepartment of Cri

erta, Edmonton, Alberta, Canada; hCardiovascular Branch, National HeartiCardiovascular Division, Department of Medicine, Brigham and Wome

husetts. *Drs. Alviar and Miller contributed equally to this work. yDrs. Sol

is workwas supported in part by theNational Institutes of Health Clinical Ce

company. All other authors have reported that they have no relationships

nuscript received January 18, 2018; revised manuscript received June 18

from 2003 to 2013 suggested that a substantial pro-portion of patients admitted to CICUs in the UnitedStates had noncardiac primary diagnoses, drivenmainly by infections and respiratory diseases (4).

Within the changing CICU environment, it hasbecome more important for cardiologists to be able tomanage aspects of their patients’ general critical care,including noninvasive positive pressure ventilation(NI-PPV) and invasive mechanical positive pressureventilation (IM-PPV) (3–5). Treatment with positivepressure ventilation (PPV) rose to nearly 15% ofadmissions in the Medicare population in 2013 (4,5).

https://doi.org/10.1016/j.jacc.2018.06.074

ACC’s) Critical Care Cardiology Working Group does

Cardiology or the ACC.

e of Medicine, Gainesville, Florida; bDivision of Car-

ecticut; cCritical Care Medicine, National Institutes of

ulmonary and Critical Care Medicine, University of

North Carolina; eDivision of Pulmonary, Allergy and

gh, Pennsylvania; fDivision of Cardiovascular Medi-

tical Care and Division of Cardiology, University of

, Lung, and Blood Institute, Bethesda, Maryland; and

n’s Hospital, Harvard Medical School, Boston, Mas-

omon and Morrow contributed equally to this work.

nter. Dr. Soble is a cofounder of Ascend, a health care

relevant to the contents of this paper to disclose.

, 2018, accepted June 19, 2018.


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TABLE 1 Basic Pulmonary Physiology and Cardiopulmonary Interactions

Ppleural Affects RV and LV Preload and Afterload

1. Ppleural is determined by the balance of the tendency of alveolar units toward collapse(elastic recoil) versus of the thoracic wall to spring outwards and action of respiratorymuscles

2. Changes in Ppleural generally influence RV inflow and LV outflow, while changes intranspulmonary pressure (Palv-Ppleural) influence RV outflow and LV inflow.

3. Negative Ppleural a) increases venous return and preload; b) decreases RV afterload; andc) increases LV afterload.

4. Positive pressure ventilation increases Ppleural and a) decreases preload; b) increases RVafterload; and c) decreases LV afterload

5. Large shifts in Ppleural (e.g., respiratory distress) can significantly increase LV afterload.

PEEP Affects RV and LV Hemodynamics

1. Total PEEP is the sum of extrinsic PEEP (generated by the ventilator) and intrinsic orauto-PEEP (due to incomplete exhalation).

2. Extrinsic PEEP is commonly used in the CICU for its beneficial effects on oxygenation,alveolar recruitment, airway patency, and preload.

3. PEEP: a) increases pulmonary vascular resistance; b) decreases RV and LV preload;c) decreases LV afterload; and d) reduces LV compliance through interventriculardependence.

4. The effect of PEEP on cardiac output varies with preload dependence and LVcontractility and compliance.

Airway Pressure Influences Hemodynamics Via its Impact on Alveolar Pressure and PleuralPressure

1. Airway pressure is determined by the flow, airway resistance, tidal volume, complianceof the chest wall and lung parenchyma, and the total end-expiratory pressure.

2. Positive pressure ventilation exerts its effects on cardiovascular hemodynamics princi-pally through its impact on Palv and Ppleural.

3. In poorly compliant lungs, changes in intrathoracic pressure will have more pronouncedeffects on hemodynamics.

LV ¼ left ventricular; Palv ¼ alveolar pressure; Paw ¼ airway pressure; PEEP ¼ positive end-expiratory pressure;Ppleural ¼ pleural pressure; RV ¼ right ventricular.

AB BR E V I A T I O N S

AND ACRONYM S

CICU = cardiac intensive care

unit

IM-PPV = invasive mechanical

positive pressure ventilation

LV = left ventricle

NI-PPV = noninvasive positive

pressure ventilation

PEEP = positive end-expiratory

pressure

Ppleural = pleural pressure

PPV = positive pressure

ventilation

PVR = pulmonary vascular

resistance

RV = right ventricle

J A C C V O L . 7 2 , N O . 1 3 , 2 0 1 8 Alviar et al.S E P T E M B E R 2 5 , 2 0 1 8 : 1 5 3 2 – 5 3 Positive Pressure Ventilation

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Cardiologists who take primary responsibility for pa-tients in the CICU should have a sophisticatedknowledge of evidence-based applications of NI- andIM-PPV and their cardiopulmonary interactions, andshould be able to tailor ventilatory strategies to anindividual patient’s underlying cardiovascular con-ditions. Moreover, any cardiologist who cares forpatients in the CICU should have a working knowl-edge of these interventions. In the first half of thisreview, we address fundamental concepts of pulmo-nary mechanics and PPV; in the second half, wediscuss specific clinical applications of these conceptsin the CICU. In each section, we have highlighted keyprinciples of broad relevance and identified thoseelements that are focused on the interests of theadvanced provider. When possible, we have aimed toprovide a practical framework or advice that may beuseful for the clinician based on the experience of thewriting group and on the available published data.Given the paucity of strong-quality studies specif-ically designed to assess PPV in the CICU, thesepractical points are not intended to be formal clinicalpractice guidelines.

BASIC CONCEPTS OF

PULMONARY MECHANICS AND

CARDIOPULMONARY PHYSIOLOGY

The cardiovascular and pulmonary systems work in aclose relationship, and changes in one system oftenaffect the other (6,7). Therefore, the basics of pul-monary mechanics are relevant to all cardiovascularproviders who care for patients undergoing PPV. Thekey concepts are listed in Table 1.

DEFINITIONS AND BASICS OF PULMONARY

MECHANICS. Intrapleural pressure (Ppleural), alsoreferred to as intrathoracic pressure, influencescardiovascular physiology. At rest, the functional re-sidual capacity is determined by 2 opposing forces:the thoracic wall with a tendency to spring outwards,and the alveolar units with a tendency to collapse. Inthe resting state, Ppleural is slightly negative(Figure 1A). During spontaneous inspiration, contrac-tion of the diaphragm and intercostal muscles rendersPpleural more negative, with resultant hemodynamiceffects (Figure 1B). During respiratory distress, otherauxiliary respiratory muscles (e.g., scalene, sterno-cleidomastoid) are recruited. Passive expirationoccurs through alveoli and chest wall recoil, makingPpleural less negative (8). In patients with obstructivelung disease, exhalation might also require an activecomponent, using abdominal muscles and intercostalmuscles during forced expiration.

Respiratory compliance and airway resis-tance are important components of the pul-monary mechanics of spontaneous breathingand PPV. Total compliance includes lungparenchymal and chest wall compliance.Lung compliance is defined as the change involume over the change in pressure (DV/DP)in the alveoli. Chest wall compliance isinfluenced by extrapulmonary factors,including obesity, thoracic cage deformities,and intrabdominal pressure, as well as,rarely, medications (e.g., fentanyl-inducedchest wall rigidity) (9). Plateau pressure(Pplat), which is relevant in patients under-going PPV, refers to the alveolar pressure(Palv) at end-inspiration and is the maximalPalv in the respiratory cycle. In ventilated
patients, Pplat is measured during an end-inspiratorypause (zero flow) and can be used to estimate totalcompliance (volume/[pplat – positive end-expiratorypressure]). Airway resistance is the change in pres-sure over flow as explained by Ohm’s law(resistance ¼ DP/flow). Airway resistance is related tothe diameter of the airways and can be influenced bybronchospasm, tracheal or upper airway pathology,mucus plugging, or airway remodeling. Increasedairway resistance will also decrease dynamic lungcompliance (Figure 2).

FIGURE 1 Effects of Pleural Pressure on Hemodynamics During Spontaneous Respiration

(A) In the resting state, Ppleural is slightly negative. (B) During spontaneous inspiration, Ppleural declines with diaphragmatic and intercostal

muscle contraction. BP ¼ blood pressure; LV ¼ left ventricular; Ppleural ¼ pleural pressure; PVR ¼ pulmonary vascular resistance; RV ¼ left

ventricular; SVR ¼ systemic vascular resistance.

Alviar et al. J A C C V O L . 7 2 , N O . 1 3 , 2 0 1 8

Positive Pressure Ventilation S E P T E M B E R 2 5 , 2 0 1 8 : 1 5 3 2 – 5 3

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Additional PPV parameters that influence cardio-pulmonary interactions require definition. First, pos-itive end-expiratory pressure (PEEP) is the pressureabove atmospheric pressure maintained throughoutthe respiratory cycle to prevent alveolar collapse at

end-expiration. Second, mean airway pressure is thearithmetic average pressure over the entire ventilatorycycle (Figure 2). Third, peak airway pressure reflectsthe pressure required to both overcome the airwayresistance and generate the tidal volume (TV). When

FIGURE 2 Pressure-Time Curve During Volume Control Ventilation

Inspiration time

Airw

ay P

ress

ure

Expiratory time

Time

Tida

l Vol

ume

Time

Average pressuresrepresented byAUC / time →Mean airway pressure

Peak inspiratory pressure (Ppeak)

Pplateau(Inspiratory hold)

Driving Pressure(ΔP) = Pplateau – PEEP

Cdyn = TV/ [Ppeak – PEEP]Cstat = TV/ [Pplat – PEEP]

PEEP

Relationship among airway pressure, flow, and time with static compliance (Cstat) and dynamic compliance (Cdyn). AUC ¼ area under the curve;

PEEP ¼ positive end-expiratory pressure; Ppeak ¼ peak pressure; Pplat ¼ plateau pressure; Ppleural ¼ pleural pressure; TV ¼ tidal volume.


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TV and compliance are constant (e.g., during volumecontrol ventilation), peak airway pressure correlateswith airway resistance. However, if lung compliance isdecreased, peak pressures will increase. MeasuringPplat by performing an end-inspiratory hold can helpdistinguish between these contributors (Figure 2). Pplat

will be higher in less compliant lungs. The fourthparameter is transpulmonary pressure, defined as thedifference between Palv and pleural pressure (Palv �Ppleural), which influences hemodynamics in the leftventricle (LV) and right ventricle (RV). Because PPVincreases both Palv and Ppleural, it can be difficult toaccurately estimate transpulmonary pressures. Foradvanced providers, an esophageal balloon can beused to estimate Ppleural and to calculate trans-pulmonary pressure if needed (10).

PULMONARY MECHANICS OF PPV. PPV creates apressure gradient between the ventilator and thepatient so that air moves in and out of the lungs asdescribed by the equation of motion:

Paw � Pmuscle ¼ F $ Rþ V=Cþ PEEPT

where Paw is the airway pressure, Pmuscle is the pres-sure generated by the patient, F is flow, R is resis-tance, V is volume, C is compliance, and PEEPT is total

positive end-expiratory pressure (11). PEEPT is thetotal of extrinsic PEEP (generated by the ventilator)and intrinsic or auto-PEEP (due to incomplete exha-lation). This equation reflects mathematically thatpeak pressure (Ppeak) in the system is the sum of thepressure at the end of expiration (PEEPT), the pres-sure created by distension of the alveoli duringinspiration (V/C), and the pressure created by resis-tance in the airways (F $ R). The pressure in thealveolus (Palv) is reflected by V/C þ PEEPT.

Extrinsic PEEP is commonly used in the CICU due tobeneficial effects on oxygenation (due to the linearrelation between PEEP and partial pressure of oxygen),alveolar recruitment, airway patency, and preload(12,13). Low levels of PEEP (w5 cmH2O) are routinelyused in intubated patients to maintain airway patencyand avoid atelectasis. Although there is no establishedoptimal PEEP, a rangewith higher levels of PEEP can beuseful for some conditions, including heart failure(HF) and noncardiogenic pulmonary edema (13,14).PEEP is generally safe when properly used and moni-tored along with Ppeak, Pplat, and TV (13).

During PPV, exhalation is a passive processduring which Palv becomes the driving pressureand progressively declines from its maximum (Pplat)down to the final end-expiratory pressure (PEEPT),

FIGURE 3 Effects of Positive Pressure Ventilation on Hemodynamics

(A) Effects of positive pressure ventilation. (B) Schematic representation of transpulmonary pressures and mean airway pressure. (C) Effects of Ppleural and trans-

pulmonary pressure. Palv ¼ alveolar pressure; Paw ¼ airway pressure; other abbreviations as in Figures 1 and 2.

Continued on the next page



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determined by its extrinsic and intrinsic componentsdefined in the previous text (Figure 2). During thisphase, Palv > Paw, which is determined by theextrinsic PEEP set by the clinician. As an advanced

concept, the amount of air trapped in the lungs at theend of exhalation depends on how quickly air exitsthe lungs, which in turn is determined by the expi-ratory time as influenced by resistance and

FIGURE 3 Continued

TABLE 2 Beneficial Effects of Positive Pressure Ventilation in Patients With Right and

Left Ventricular Dysfunction

Mechanism Effect

Direct effectsfrom PEEP

� Decreases LV afterload� Decreases LV diameter,

leading to decreased MR

� LV unloading� Improved cardiac output

� Increases transmural pressure � Improved cardiac output

� Increases Palv at the endof expiration

� Improved compliance(i.e., prevention of alveolarcollapse)

Effects from or ongas exchange

� Reverses hypoxicvasoconstriction

� Lower RV afterload

� Decreases in preload � Improved pulmonarycongestion

� Improves ventilation/perfusion matching

� Improved oxygenation

Effects fromventilatory support

� Improves work of breathing � Improved tissue perfusion� Decreased myocardial

consumption of oxygen

� Improves hypercarbia andacidosis

� Improved RV afterload

Systemiceffects

� Optimizes gas exchange,hence oxygenation andtissue perfusion

� Improved metabolic demandand peripheral perfusion

FIO2 ¼ fraction of inspired of oxygen; MR ¼ mitral regurgitation; Palv ¼ alveolar pressure; other abbreviations asin Table 1.


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compliance. Patients with high resistance (e.g.,chronic obstructive pulmonary disease [COPD]) needlonger exhalation time and are more prone to devel-oping auto-PEEP, especially in those with high lungvolumes (e.g., emphysema).

When considering the management of PPV in thecardiac patient, as described in the sections that follow, afundamental concept is that the patient’s airway andlung characteristics (resistance and compliance) deter-mine the relationship between physician-set parametersand resultant volume, pressures, and flow.

PPV AND LV PHYSIOLOGY. PPV exerts its effects oncardiovascular hemodynamics principally through itseffect on Palv and Ppleural. Both Ppeak and end-expiratory pressure (determined by PEEP) influencehemodynamics (Figure 3). Transpulmonary pressurealso affects the RV and LV. In general, changes inPpleural influence inflow to the RV and outflow fromthe LV, whereas changes in transpulmonary pressure(Palv-Ppleural) influence outflow from the RV andinflow to the LV by affecting the pulmonary vascu-lature. Hence, when Ppleural drops, LV systolic pres-sure becomes more negative relative to systemiccirculation increasing LV afterload (Figure 3C) (15).

CENTRAL ILLUSTRATION Potential Physiological Effects of Positive End-Expiratory Pressure on VentricularFunction and Cardiac Output

Clin

ical

Pea

rls Net effect of positive end-expiratory pressure (PEEP) on cardiac output (CO) depends on RV/LVfunction, preload, afterload, and ventricular interdependence.In RV failure/preload dependence, moderate to high PEEP (5-15 cmH2O) may decrease RV CO.In afterload dependent states (e.g., LV failure), moderate to high PEEP (10-15 cmH2O) may improve CO.

•

••

PEEP↓↓CO ↑CO

Hypoxia mediated pulmonaryvasoconstriction

Righ

t Ven

tric

le

Compensatory increase in systemic vascular resistance

Right ventricular (RV) venous return

Pulmonary vascular resistance due to vascular compressionRV dilation → left shift in septum

Left

Ven

tric

le

Preload due to lower RV outputStroke volume due to interventricular dependence

Left ventricular (LV) afterloadLV preload and LV dilatationMyocardial oxygen demand

Pressure gradient from thorax toperipheryHydrostatic displacement ofalveolar edema

Alviar, C.L. et al. J Am Coll Cardiol. 2018;72(13):1532–53.

Positive end-expiratory pressure (PEEP) will have variable effects on cardiac output (CO) depending on left ventricular (LV) and right ventricular (RV) function, preload

and filling pressures. Note that in patients with noncompliant lungs from causes other than cardiogenic pulmonary edema, the effect of PEEP on Ppleural and pre-load

might not be as pronounced.



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Experimental and in vivo studies have demon-strated interactions between PPV and LV preload andafterload (Table 2) (6,7,16). During PPV, LV wall ten-sion remains constant due to an equivalent increasein the Ppleural, aortic pressure, and LV pressure,generating a flow gradient between thorax and pe-ripheral organs (intra-aortic balloon pump-like effect)(Online Figure 1). When Ppleural increases, aorticpressure initially goes up, triggering autoregulationby peripheral baroreceptors lowering systemicvascular resistance and LV afterload (17), improvingcardiac output (CO) (Figure 3A) (14). Additionally, inpatients with a dilated LV and high filling pressures inwhom functional mitral regurgitation (MR) impairsCO, PEEP can improve ventricular diameter and MR

(18,19). In addition, through ventricular interdepen-dence, influences of PPV on the RV may ultimatelyaffect LV performance. A pressure overloaded anddilated RV can displace the interventricular septumtoward the LV, decreasing LV pre-load and strokevolume (Online Figure 2) (20,21). These effects ofPEEP on LV and RV hemodynamics will determine thenet influence on CO (Central Illustration).PPV AND RV PHYSIOLOGY. PPV can have importanteffects on RV preload, afterload, and myocardial perfu-sion. During spontaneous breathing, the negative Ppleural

created during inspiration augments venous return,preload, and RV filling (22). Because the pressure gradientbetween the venous circulation and the RV is normallyonly about 4 to 8 mmHg (23), small changes in Ppleural can



FIGURE 4 Relationship Between Alveolar Volume/Pressure and Pulmonary

Vascular Resistance

Very high PEEP/Palv

will compressPulmonary vesselsand increase PVR

Opening alveoli withappropriate PEEP willfavorably tethervessels and improvePVR

OverdistensionAtelectasis

Lung Volume (ml)PV

R

At low lung volumesatelectasis can increasePVR due to collapse of thealveolar-capillary unit andhypoxic vasoconstriction

Adapted from West JB, Luks AM. West’s Respiratory Physiology: The Essentials. Phila-

delphia, PA: Wolters Kluwer Health Ed, 2015;92. PEEP ¼ positive end-expiratory pres-

sure; PVR ¼ pulmonary vascular resistance. Blue vessel represents deoxygenated blood.

TABLE 3 Indications and Contraindications to Noninvasive Positive Pressure Ventilation

Indications for NI-PPV Contraindications to NI-PPV

� Cardiogenic pulmonary edema� Hypercapnic respiratory failure� COPD exacerbation� High-risk extubation� Immunocompromised patient with

respiratory failure� Neuromuscular disease� Trauma (chest trauma)� Ventilatory support in the

palliative patient� Post-operative hypoxic

respiratory failure

� Need for effective airway protectionbecause of altered mental status,uncooperative patient, apnea, cardiacarrest, or seizures

� Facial deformities because of pathology,recent surgery, or trauma

� Hemodynamic instability� Aspiration risk (emesis, inability to control

secretions)� Recent upper airway or gastrointestinal

surgery

COPD ¼ chronic obstructive pulmonary disease.


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produce relatively large effects on venous return and CO(22,23). When Ppleural drops, the extrathoracic venous-to-RV gradient increases and preload increases.

In contrast, during PPV, the ventilator generatespositive Paw, transmitted into Palv and Ppleural, leadingto a positive transpulmonary pressure (Palv-Ppleural).Both PEEP and mean Paw have a direct effect on theloading conditions of the heart (Central Illustration).During invasive and noninvasive PPV, increased PEEPand Ppleural decrease venous return and thus RVpreload (Figure 3) (15). At the same time, PPV in-creases RV afterload by increasing transpulmonarypressure causing microvascular collapse andincreasing pulmonary vascular resistance (PVR).Similarly, the use of PEEP can increase RV afterload.Through its effects on lung volume, PEEP has aU-shaped effect on PVR. By relieving atelectasis,PEEP can open alveoli, enhance lung volume, andfavorably tether blood vessels, decreasing PVR andimproving blood flow (24). However, high PEEP cancause alveolar overdistension compressing extra-alveolar vessels, increasing PVR, and leading to aredirection of blood flow to poorly ventilated areas,which increases V/Q mismatch with consequenthypoxia and hypercarbia (Figure 4) (25).

Changes in Ppleural reflecting changes in Palv fromPEEP are highly dependent on alveolar compliance.For instance, in patients with cardiogenic pulmonaryedema (CPE), lung compliance is decreased due tointerstitial edema and fluid-filled alveoli. As PEEPdecreases preload and concomitantly creates hydro-static pressure that forces fluid out of the alveoli,compliance and gas exchange improve, and thus sodoes PVR. However, in patients with noncompliantlungs from other causes (e.g., acute respiratorydistress syndrome [ARDS]), the effect of PEEP onPpleural and preload is not as pronounced. In suchpatients, even small amounts of PEEP with smallchanges in Palv can increase RV afterload dispropor-tionally by worsening PVR and impairing pulmonaryblood flow (26). Patients with RV dysfunction areparticularly sensitive to this adverse effect on PVR(Central Illustration).

Myocardial perfusion of the RV is dependent onPpleural, RV pressure, and aortic pressure, and there-fore is affected by PPV. During PPV in normotensivepatients, aortic pressure remains higher than Ppleural

and RV pressure, maintaining myocardial perfusion.However, in patients with low aortic pressure (e.g.,shock), RV perfusion can be compromised by elevatedPpleural from high PEEP or high Paw (27). The limitedmyocardial mass of the RV wall makes it moresensitive to changes in afterload than to changes inpreload (17), while the opposite is true for the LV

(Online Figure 3). Therefore, taking each of thesepotential adverse effects into consideration, PEEPshould be used with caution in patients with RVfailure (17). Moreover, in patients with RV dysfunc-tion secondary to obstructive lung disease (e.g.,COPD), monitoring for and preventing auto-PEEP isparticularly important to avoid precipitating hemo-dynamic instability and to prevent barotrauma(Online Figure 4) (28).

MODES AND APPLICATIONS OF

OXYGENATION AND VENTILATORY SUPPORT

IN THE CICU

HIGH-FLOW NASAL CANNULA. Standard nasalcannulas are limited to a maximum flow of 6 l/min,and may not meet the demands of the severely hyp-oxemic patient. By comparison, high-flow nasal can-nulas (HFNCs) deliver a heated and humidified flow



FIGURE 5 Schematic Overview of Ventilator Modes and Settings

Clinician Sets Pressure

PressureControl

AC orSIMV†

FIO2 21-100%

5-10 cmH2OInitial PEEP

RespiratoryRate (RR)

Tidal Volume Variable depending on resistance, compliance andpatient effort.

Minimum Set RR;May breathe above RR

F, P or t for mandatorybreaths; F or P for

spontaneous breathsF or P for all breaths.

Set (Constant)

Set (Constant)

Guaranteed airway P (PIP = PC + PEEP)Minimum set RRF & TV adjust to patient demand

Pplat is not guaranteedThe set expiratory threshold must be matched to patient

Pplat is not guaranteedThe set expiratory threshold must be matched to patient

Pplat is not guaranteedThe set IT must be matched to patient

Potential patient fatigue if asynchronyVigorous patient effort leads to paradoxical under-support

Potential patient fatigue if asynchronyVigorous patient effort leads to paradoxical under-supportPotential diaphragm atrophy from over- support

Minimum rate notguaranteed*

Minimum rate notguaranteed*

TV not guaranteed TV not guaranteed TV can be higher than set TV with patient effort

TV can be higher than set TV with patient effort

Pplat is not guaranteedThe set IT/flow must be matched to patient

Potential patient fatigue if asynchrony

Potential diaphragm atrophy from over- support

F dose not adjust to meet patient demand

Pplat is not guaranteedThe set IT must be matched to patient



Potential diaphragm atrophy from over- support

Guaranteed airway P (PIP = PS + PEEP)Patient sets own RRF & TV adjust to patient demand

Minimum TV

Patient sets own RRF adjusts to patient demand

Minimum TV & MV

Minimum set RRF adjusts to patient demand

Guaranteed TVMinimum MVMinimum set RR

Variable depending on resistance, compliance and patient effort. Decelerating if no patient effort.

Set (Constant) Set (Constant)$

Set (Square orDecelerating)

Inspiration ends when F decreases to an expiratorythreshold (% of peak flow) which can be set by the

clinician in most machines.

Variable depending on resistance, compliance and patient effort.

F, P or t for mandatory breaths;F or P for spontaneous breaths

Patient sets own RR* Minimum Set RR;May breath above RR

Ventilator automatically adjusts P to achieve thetargeted TV but TV can vary breath to breath. Set (Constant)

Trigger

PeakPressures

InspiratoryTime (IT)

Flow Pattern

Advantages

Disadvantages

AC orSIMV†

SpontaneousVentilation

PressureSupport

VolumeSupport

VolumeTarget

VolumeControl

Clinician Sets Volume

Each of the settings set by the clinician and the resulting ventilatory parameters are shown for the major modes of positive pressure ventilation. More advanced modes

and breath types (proportional assist ventilation, neurally adjusted ventilatory assist, and airway pressure release ventilation) are not described. Green ¼ variable set

(constant) by the clinician; orange ¼ variable changes according to patient-ventilator interaction. *Classically no back up. Alarm can be set if patient’s RR is < set limit.

†For SIMV mode (SIMV PC, SIMV VC, or SIMV Volume Target), the descriptions apply only to set breaths and not spontaneous breaths. $For some machines, clinician

sets TV and flow pattern, which determines IT. For other machines, IT is set directly. A/C ¼ assist control; F¼ flow; FIO2 ¼ fraction of inspired oxygen; IT ¼ inspiratory

time; MV ¼ minute ventilation; P ¼ pressure; PC ¼ pressure control; PEEP ¼ positive end expiratory pressure; PIP ¼ peak inspiratory pressure; Pplat ¼ plateau pressure;

PS ¼ pressure support; R ¼ resistance; RR ¼ respiratory rate; SIMV ¼ synchronized intermittent mandatory ventilation; t ¼ time; TV ¼ tidal volume.



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of up to 60 l/min (29). By using flow rates higher thanthe inspiratory demand of the patient, HFNC canprovide reliable inspired FiO2 (30). Along withimproved oxygenation, with high flow rates, HFNCprovides up to w7 cmH20 of PEEP (29). Although 1

randomized trial has suggested lower mortality withHFNC compared with NI-PPV (31), other trials haveindicated similar outcomes (32). There are norandomized controlled trials of HFNC specifically inpatients with CPE (33).

TABLE 4 Simplified Approach to Modes of Invasive Mechanical

Positive Pressure Ventilation

Volume Control VentilationPressure Control

VentilationPressure Supported

Ventilation

� The independent variable isvolume and flow

� The independent variable ispressure

� The dependent variable ispressure

� The dependent variables arevolume and flow

TABLE 5 Advantages and Disadvantages of PS Mode

Pressure Supported Ventilation

Advantages Disadvantages

1. The patient can control the depth, length,and flow of each breath

2. Allows flexibility in ventilator support3. Improves synchrony and diaphragmatic work

� Excessive level of support can result in:1. Respiratory alkalosis2. Hyperinflation3. Ineffective triggering4. Apneic spells

� Suboptimal support can result in:1. Diaphragmatic fatigue2. Respiratory acidosis

PS ¼ pressure support.


1541

NONINVASIVE PPV. NI-PPV is an important modalityfor management of patients in the CICU. NI-PPV in-cludes continuous positive airway pressure (CPAP)and bilevel positive airway pressure (BiPAP). WhereasCPAP provides continuous PPV, BiPAP providesseparately titratable inspiratory positive airwaypressure (IPAP) and expiratory positive airway pres-sure (EPAP) (which is functionally equivalent to PEEPin IM-PPV). BiPAP can reduce work of breathing, in-crease TV more than CPAP, and improve ventilationin patients with hypercarbia. Proper patientselection is integral to the successful use ofNI-PPV (Table 3) (34).

There are several interfaces available for NI-PPV,including a total face mask (covering nose, mouth,and eyes), oronasal or full-face mask, nasal mask, andnasal pillows. Although all masks have advantagesand disadvantages (Online Table 1), a mask coveringboth the nose and mouth is preferable to minimizeleaks (35).

Initial NI-PPV settings in randomized controlledtrials have varied. CPAP and EPAP are generallytitrated to oxygenation, and IPAP (BiPAP only) is usedto control ventilation (PaC02). For CPAP, a typicalstarting pressure is 5 to 10 cmH2O, with titration by2 cmH2O. If BiPAP is used, initial settings are oftenIPAP of 10 cmH2O and an EPAP of 5 cmH2O. Titrationof the IPAP upward by 2 to 3 cmH2O can be made toimprove hypercapnia, avoiding IPAP >20 cmH2O toprevent gastric insufflation and minimize aspirationrisk (36). The FiO2 may start high and be titrated to agoal Sa02 (e.g., 94% to 98%) while avoidingSa02 >98%. A trend in consensus toward avoidinghyperoxemia originates with observed associationsbetween 02 therapy in nonhypoxemic patients andhigher mortality (37), including some cardiovascularconditions, such as acute coronary syndromes, heartfailure, stroke, and post-cardiac arrest (38,39).

If NI-PPV is going to be successful, the patient willgenerally show improvement, such as a decrease inrespiratory rate, improved work of breathing, andimproved gas exchange, in 1 to 2 h.

In well-selected patients, adverse effects are fewand mostly related to the tolerability of the device/mask (40,41). More serious adverse effects can occur,including aspiration, mucus plugging, or hypotension(40). Online Table 2 describes factors associated withNI-PPV failure.

INVASIVE MECHANICAL PPV. Indications for IM-PPVinclude refractory hypoxia or hypercarbia, unsus-tainable work-of-breathing, and need for airwayprotection in the setting of altered mental status,cardiorespiratory arrest, impending hemodynamic/

respiratory collapse, active vomiting, or uppergastrointestinal bleeding. Modes of IM-PPV are pre-set algorithms that dictate the pattern of mandatoryand spontaneous breaths delivered by the ventilatorand translate into specific patient-ventilatorinteractions. The mode should be tailored to theclinical scenario to provide greatest benefit with thelowest risk of complications, while optimizingpatient comfort and ease of liberation fromIM-PPV (42).

More than 300 proprietary names represent about50 modes. There are no compelling data to supportthe superiority of any specific mode for a given dis-ease in adults. Although there is no consensus toclassify IM-PPV modes, a simplified nomenclature hasbeen proposed (42) based on three factors: The con-trol variable (pressure, or volume/flow), the breathsequence (continuous mandatory ventilation, inter-mittent mandatory ventilation, or continuous spon-taneous ventilation), and the targeting scheme (aspecific ventilator pattern in response to patient-ventilator feedback) (Online Figure 5). Details of thistaxonomy are explained elsewhere (42).Management of vent i la tor set t ings . When initi-ating and managing IM-PPV, 4 key elements (trig-gering, inspiratory control variable, cycling, andexpiratory period PEEP) need to be considered inrelation to each phase of a breath. These elements areincluded in Figure 5 and are explained in detail for theinterested reader in Online Table 3. The control var-iable is selected by the clinician and describes howthe ventilator regulates the amount of volume or





FIGURE 6 Effect of Auto-PEEP on Volume-Control Ventilation and Pressure-Control Ventilation

↑Paw – Pmuscle = F*R + V/C + ↑PEEPT

Paw – Pmuscle = ↓F*R + ↓V/C + ↑PEEPT

Paw – Pmuscle = F*R + V/C + PEEPT

Equation of motion

autoPEEPduring PCV

autoPEEPduring VCV

↑Palv

If ↓ V and ↓F is excessiverespiratory acidosis can occur

and cause hemodynamiccompromise

If ↑ Paw and ↑Palvis excessive, alveolar

overdistention can occur andcause hemodynamic

compromise

As auto-PEEP increases, a compensatory effect will occur on flow (F), volume (V), Paw, and Palv. If auto-PEEP is not addressed, hemodynamic

compromise will ultimately occur by respiratory acidosis (during pressure control) or alveolar overdistension (during volume control). Ab-

breviations as in Figures 2 and 3.



1542

pressure to deliver in each breath including pressurecontrol ventilation or volume control ventilation.Another control type is volume-targeted ventilation,which is a dual-control mode with a set target TV,allowing the ventilator to automatically adjust thepressure level to achieve the targeted TV (e.g., “VCþ”

or “autoflow”).Currently, the most commonly used modes of

IM-PPV can be classified by a simplified approachinto pressure control, volume control, and pressuresupport (Tables 4 and 5). These modes can be sub-divided into assist control, synchronized intermittentmandatory ventilation (SIMV), and spontaneousventilation (Figure 5). The distinguishing feature ofassist control is that spontaneous patient effortresults in delivery of an identical breath as themandatory breath (same TV or driving pressure,same inspiratory time/flow pattern) (Figure 5). Incontrast, during SIMV, these clinician-selected set-tings apply only to the mandatory breaths, whilespontaneous breaths differ by being completelyinitiated and terminated by the patient effort withwhatever volume, pressure, or flow the patient canexert without any ventilator assistance. SIMV is aform of intermittent mandatory ventilation. In thespontaneous ventilation mode, the clinician sets theFIO2, PEEP, and supporting volume or pressure, butnot the respiratory rate, inspiratory time, or flowpattern, so the patient must initiate all breaths. Anadditional mode, airway pressure release ventilation(APRV), is a pressure control ventilation mode used inpatients with refractory hypoxia. APRV has a pro-longed inspiratory phase in an inverse ratio

ventilation, where unrestricted spontaneous breath-ing can occur at any time (43).

No ventilator mode is optimal for all cardiac pa-tients. However, modes that allow full spontaneousbreaths with no ventilator assistance (e.g., SIMV) canincrease afterload and myocardial oxygen consump-tion when some of the spontaneous breaths are notfully supported, potentially leading to patient-ventilator dyssynchrony. Such modes might not beoptimal for cardiac patients with cardiogenic shock ormyocardial ischemia (44–46). Finding the appropriatelevel of support mitigates diaphragmatic fatigue andavoids diaphragmatic atrophy, both of which can in-crease duration of mechanical ventilation (47).Although there are no proven strategies to preventdiaphragmatic dysfunction, using minimally neces-sary supportive settings is reasonable.

After selecting a ventilator mode, the clinician isresponsible for setting up the individual parameters(Figure 5, Online Table 4). FiO2 and PEEP havedominant effects on oxygenation and should beadjusted to achieve an acceptable oxygen saturation(SaO2), with early de-escalation of FiO2 to minimizethe risk of oxygen toxicity. PEEP is typically set at5 cmH2O and can be adjusted to the desired SaO2

while taking in consideration the effects of excessivePEEP (e.g., decreased preload, barotrauma) and thoseof inappropriately very-low PEEP (e.g., atelectrauma)as well as the effects on the RV and LV.

The product of TV and respiratory rate (minuteventilation) predominantly affects PCO2 and pH. TVshould be set not to exceed 6 to 10 ml/kg (6 to 8 ml/kgof ideal body weight for ARDS), while keeping


FIGURE 7 Example Algorithm for Oxygen Therapy and NI-PPV in Patients With Pulmonary Edema

Pulmonary edema withrespiratory insufficiency

Respiratory Support in Pulmonary Edema

Respiratory distress orO2 saturation <92%

Oxygen therapy

Persistent Respiratory distress:Respiratory rate >20-25 breaths/min, or

Increased work of breathing

Non-Invasive Ventilation

Hypoxia withhypercapnia

Hypoxia alone

HFNC

No

BiPAP• Initial IPAP: 10 cmH2O - Titrate 2-3 cmH2O to improve ventilation - Avoid IPAP >20 cmH2O to prevent gastric insufflation & minimize aspiration risk• Initial EPAP: 5 cmH2O

CPAP• Initial Pressure: 5-10 cmH2O - Titrate by 2 cmH2O as tolerated

Stabilized

Oxygen therapy

• Decreased work-of-breathing• Decreased respiratory and heart rate• SaO2 between 94-98%

Improvement within 60 minutes

Yes

No

Invasive Mechanical Ventilation

Consider immediate intubation if respiratory distresssevere or contraindications to non-invasive ventilation

Continue oxygen therapy(nasal cannula, face

mask)

BiPAP ¼ bilevel positive airway pressure; CPAP ¼ continuous positive airway pressure; EPAP ¼ expiratory positive airway pressure;

HFNC ¼ high-flow nasal cannula; IPAP ¼ inspiratory positive airway pressure.


1543

Pplat <30 cmH20 to minimize the risk of alveolaroverdistension. Although low TV ventilation has beenstudied predominantly in ARDS, overdistension fromhigh TV might also be harmful in cardiac patientsaccording to 1 study, which showed that TV >9.3 ml/kgof ideal body weight was associated with adverse out-comes in the CICU (48). Inappropriately high TV may

cause “volutrauma” from overdistension, but inappro-priately low TV can cause atelectasis, patient-ventilatordyssynchrony, and suboptimal gas exchange.

The respiratory rate can be adjusted to achieveacceptable PCO2 and pH for the patient’s needs (e.g.,permissive hypercapnia for refractory hypoxia duringARDS may be appropriate, whereas limiting acidosis

FIGURE 8 Example Algorithm for IM-PPV in Patients With Heart Failure or Cardiogenic Shock

Use PPV only when necessaryOptimize MAP (>60 mmHg) with vasopressorsOptimize preload (RA pressure >8 & <14 mmHg)Consider etomidate, ketamine, benzodiazepines oropiates for induction. Caution with propofol.Consider awake intubation if tamponade/constriction

••••

•

Ensure adequate volume status firstIf PCWP 12-15 mm Hg, start PEEP at 5-10cmH2O Adjust according to O2Sat >92%If PCWP elevated (>15 mm Hg) PEEP canbe increased to 8-10 cmH2O withmonitoring of CO (CO might improve)

••

••

Keep RA pressure >8 and <14 mm Hg, and MAP >60 mm HgStart PEEP 3-5 cmH2O and use the lowest possible to achieve safeoxygen targets (O2Sat >92%)If acidosis present, ventilate to normal pH to improve PVRConsider using pulmonary vasodilators for refractory hypoxia if PVRis >3 Wood units provided that the PCWP is <18 mm HgIf alveolar consolidation, consider an inhaled pulmonary vasodilator(e.g. nitric oxide or epoprostenol) to improve ventilation perfusionmismatch

••

••

•

Early intubation todecrease myocardialoxygen consumption

RV failure ortamponade present?

Adjusting PEEP

Mode: AC (PC-CMV, VC-CMV). PS can also be used with closemonitoring of work of breathing. No evidence to support onemode over others.FIO2: Start with 100% → rapid down-titration to O2Sat >92%TV: Start with 6-10 ml/kg of IBW (6-8 ml/kg if ARDS) → adjust toPCO2 while avoiding volutrauma or atelectasis and maintaininga plateau pressure <30 cmH20.RR: Start with 10-20 breaths/min → adjust to PCO2 whilemonitoring auto-PEEPEnsure proper sedation to maintain synchrony

•

••

•

•

Initial ventilator Settings

No RV failure present“Afterload dependent”

RV failure present or other “Preloaddependent” states (e.g. tamponade)

Consider timing the removal of femoral devicesrelative to extubation to avoid vascularcomplications while allowing optimalpositioning of patient for extubation.

Tip for weaning mechanical ventilation:

Patient with acute heart failure or cardiogenic shock

Severe HypoxiaIncreased work of breathingFailure to respond to non-invasive positive pressure ventilationClinical instability due to refractory shockNeed for mechanical circulatory support in combination withrespiratory failure Patients undergoing targeted temperature management

•••••

•

Consider potential indications for IM-PPV:

If respiratory failure and cardiogenicshock, biventricular failure orrefractory shock are present, thenconsider extracorporeal life supportwith protective lung ventilation.

The acuity of RV failure will influencehemodynamics (e.g. RV infarct versuslong standing RV failure orpulmonary HTN).

ARDS ¼ acute respiratory distress syndrome; CO ¼ cardiac output; IBW ¼ ideal body weight; IM-PPV ¼ invasive mechanical positive pressure

ventilation; MAP ¼ mean arterial pressure; PCWP ¼ pulmonary capillary wedge pressure; PVR ¼ pulmonary vascular resistance; RA ¼ right

atrium; other abbreviations as in Figure 5.



1544

and hypercapnia is beneficial in patients with RVdysfunction). It is important to underscore that datafrom studies in pulmonary syndromes may not beextrapolated to all cardiac patients, highlighting theneed for research specifically done in CICU settings.

Each ventilator setting has both intended ben-efits and potential adverse consequences; there-fore, to assess the patient’s response to IM-PPVand risk of complications, the clinician mustmonitor the hemodynamics, blood gases, TV,

TABLE 6 Cardiovascular Effects of Key Agents Used in the Management of PPV in the CICU

Drug Class/Common Agents Drug Dosage

PharmacologicalClass

Most Frequent AdverseCardiac Effects Comments

Sedation/inductionagents

All agents can worsen myocardial dysfunction.

Propofol Bolus: 0.25–2.00mg/kg IV

Infusion: 5–50mg/kg/min IV

General anesthetic Hypotension, bradycardia Hypertension and tachycardia are also possible.Caution if LVEF <50%. Monitor for propofol-related infusion syndrome, a rare but importantside effect. Negative inotropic effect, especiallywhen infused as a bolus.

Etomidate 0.3–0.4 mg/kg IV General anesthetic Hypotension because ofadrenal suppression

Single dose inhibits adrenal steroid production for 6–24 h; hence, need to closely monitor fluid balancein patients with heart failure. May require stresssteroids. Concerns for adrenal insufficiency havebeen raised, but it has not been demonstrated toincrease mortality in septic patients.

Useful for intubation in RV failure.Consider an alternative agent in patients with sepsis

(e.g., ketamine, methohexital).

Dexmedetomidine Loading: 1 mcg/kg over10 min IV

Infusion: 0.2–0.7mg/kg/h IV* for 24 h

a2 adrenergic agonist,sedative

Hypotension, bradycardia Hypotension due to cardiovascular depression andhypertension due to peripheral vasoconstriction(a2B receptor-mediated) have been describedduring bolus dosing.

Hypertension and tachycardia may improve with dosereduction. Caution if pre-existing heart block orbradycardia.

Methohexital Loading: IV: 0.75–1.00 mg/kg; canre-dose 0.5 mg/kgevery 2 to 5 min asneeded

General anesthetic(barbiturate derivative)

Hypotension, tachycardia Hypotension due to cardiovascular depression andtachycardia.

Ketamine Bolus: 0.1–0.5 mg/kg IVInfusion: 5–20

mg/kg/min IV

General anesthetic Hypertension, tachycardia Hypotension may also occur. Reactions may requireadditional sedation with other agents; use withcaution in CAD and catecholamine depletion, suchas in states of prolonged illness/hospitalization.

Although superiority over other agents has not beendemonstrated, ketamine may cause lesshypotension by increasing systemic vascularresistance, so careful patient selection andmonitoring in patients with LV dysfunction andhypertension is warranted.

Useful for intubation in RV failure in patients withoutsuspicion for catecholamine depletion.

Neuromuscularblockade agents

Ensure adequate sedation and analgesia if using NMB;monitor NMB through stimulation of peripheralnerves (79).

Succinylcholine Bolus: 1–2 mg/kg IV Depolarizingneuromuscularblockade

Bradycardia (most often inchildren); hypotension,hypertension, tachycardia;

Arrhythmias because ofhyperkalemia

Avoid if severe electrolyte abnormalities includinghyperkalemia, muscle disorders, plasma pseudocholinesterase disorders.

Rocuronium Bolus: 0.6–1.2 mg/kg IVInfusion: 4–16

mg/kg/min IV

Nondepolarizingneuromuscularblockade

Infrequent side effects (<1%);Anaphylaxis,hypersensitivity reactions;Hypertension, tachycardia

Use with caution in conditions that potentiate orantagonize NMB.

Maintenance bolus dosing used in operating room.

Vecuronium Bolus: 0.08–0.10mg/kg IV

Infusion: 1 mg/kg/min IV


Infrequent side effects (<1%);Hypersensitivity,bradycardia, hypotension;

Cross-reactivity with otherNMBs


Maintenance bolus dosing used in operating room.

Cisatracurium Bolus: 0.15–0.20mg/kg IV

Infusion: 0.5–10.0mg/kg/min IV


Infrequent side effects (<1%);Hypersensitivity,bradycardia, hypotension;

Cross-reactivity with otherNMB


Maintenance bolus dosing used in operating room.May be preferred in ARDS.

Continued on the next page


1545

minute ventilation, Pplat, auto-PEEP, and patient-ventilator interactions. The clinician needs to bemeticulous about avoiding auto-PEEP by allowingadequate exhalation time or by adjusting flow

curves and inspiratory flow velocities. Auto-PEEPcan lead to progressive air trapping and cancompromise preload if not detected and resolved(Figure 6).

TABLE 6 Continued

Drug Class/Common Agents Drug Dosage

PharmacologicalClass

Most Frequent AdverseCardiac Effects Comments

Reversal agents

Sugammadex Bolus: 2–16 mg/kg IVdepending on level ofblock

Selective relaxant bindingagent

Anaphylaxis is majorside effect,

Hypotension, hypertension,bradycardia, tachycardia,QT prolongation

Reverses neuromuscular blockade only for rocuroniumand vecuronium, not nonsteroidal neuromuscularblocking agents such as succinylcholine orbenzylisoquinolinium compounds.

Naloxone 0.4–2.0 mg IV, can berepeated at 2–3 minintervals to maximumdose 10 mg

Opioid antagonist Flushing, hypertension,hypotension, arrhythmias

For reversal in chronic use cases, reduce dose and/ordilute in 10 ml 0.9% NaCl. Infuse slowly, to avoidacute opioid withdrawal and catecholaminerelease that can be very concerning in cardiacpatients.

Analgesics

Fentanyl Bolus: 25–75 mgq1–2 h IV

Infusion: 50–100mcg/h IV

Anilidopiperidineopioid; generalanesthetic

Hypotension, bradycardia Many other reported adverse reactions. Fentanyl-induced chest wall rigidity (rare complication).

Other dose ranges depend on diagnosis and route ofadministration.

Hydromorphone Bolus: 0.2–0.6 mgq1–2 h IV

Infusion: 0.5–3.0 mg/h IV

Opioid Hypotension, bradycardiaHypertension, tachycardia

Dose varies depending on route of delivery.

Morphine Bolus: 2–5 mg q4 h IV forpain

Infusion: 2–30 mg/h IV

Opioid Bradycardia, tachycardia,hypotension; histaminerelease

Dose varies depending on route of delivery.Has a venodilatory effect so it should be used with

caution in preload–dependent states (e.g., RVfailure).

Methadone 2.5–10.0 mg q8–12 h IV or10–40 mg q6–12 hby mouth

Opioid Hypotension, arrhythmias,QT prolongation

Monitor QT interval; discontinue if significant QTprolongation.

Dose varies depending on route of delivery andpatient.

Half-life variable and very long.

Ketorolac Bolus: 30 mg IV, then15-30 mg q6 h up to

5 days

NSAID Edema, hypertension,hyperkalemia

Adjust dose for weight <50 kg, age $65 yrsand renal impairment.

Contraindicated in setting of coronary artery bypasssurgery.

Anxiolytic agents

Midazolam Bolus: 0.01–0.05mg/kg IV

Infusion: 0.02–0.10 mg/kg/h IV†

Anticonvulsant,benzodiazepine

Hypotension, especially inchildren

Lorazepam Bolus: 0.02–0.04 mg/kg(max 2 mg perdose) IV

Infusion: 0.01–0.10 mg/kg/h IV†

Anticonvulsant,benzodiazepine

Hypotension Monitor for propylene glycol toxicity, especially ifdoses above 0.1 mg/kg/h and/or renal failure.

Antipsychotic/hypnoticagents

Quetiapine No intravenous dosing.For ICU delirium: 50 mg

by mouth twice daily;may increase tomaximum dose200 mg twice daily‡

Atypical antipsychotic, 2ndgeneration

Hypotension, hypertension,tachycardia

Monitor QT interval, discontinue if significant QTprolongation.

Haloperidol Bolus: 0.5–10.0 mgq2–4 h IV

Infusion: 0.5–2.0 mg/h IV

Typical antipsychotic, 1stgeneration

Hypotension, hypertension,arrhythmias

Monitor QT interval, discontinue if significant QTprolongation.

Information abstracted from Barr et al. (88) and deBacker et al. (87). *Higher infusion rates up to 1.5 mcg/kg/h are reported and infusions have extended to several days. †Dose for ICU sedation; may vary inother circumstances. ‡Dosage varies based on condition being treated.

ARDS ¼ acute respiratory distress syndrome; CAD ¼ coronary artery disease; ICU¼ intensive care unit; IM¼ intramuscular; IV ¼ intravenous; LVEF¼ left ventricular ejection fraction; NMB¼ neuromuscularblockers; NSAID ¼ nonsteroid anti-inflammatory drugs; RV ¼ right ventricle; SC ¼ subcutaneously.



1546

APPLICATIONS OF PPV IN

CARDIAC PATIENTS

NI-PPV IN CARDIOGENIC PULMONARY EDEMA.

Among critical cardiac conditions, CPE complicates

15% to 40% of HF admissions. Often, supplementaloxygen alone is insufficient for CPE, and moreadvanced support is necessary with NI-PPV. Throughmechanisms already described in this review, NI-PPVincreases intrathoracic pressure, reduces RV and LV


1547

preload and LV afterload (5,49), improves dyspnea,and augments oxygenation (41,50,51). Further,hospitals that use NI-PPV have lower intubationrates (52).

The 3CPO (Three Interventions in CardiogenicPulmonary Oedema) (41) was a multicenter, ran-domized, controlled trial that compared CPAP(n ¼ 346) and BiPAP (n ¼ 356) with standard oxygentherapy (n ¼ 367) in patients with CPE. At 7 days,there was no difference in the primary outcome ofmortality comparing NI-PPV with standard oxygentherapy (9.5% vs. 9.8%; p ¼ 0.87). Furthermore, therewas no difference in the combined endpoint of deathor intubation rate between NI-PPV types. However, at1 h, there were significant improvements in dyspnea,heart rate, acidosis, and hypercapnia with NI-PPV(41). This study was limited by low intubation ratesand mortality, and considerable crossover betweengroups. In contrast, 2 subsequent meta-analyses re-ported reduced in-hospital mortality and intubationswith NI-PPV in CPE (53,54), but most of the includedtrials were small, of lower quality, and with variabledefinitions and severity of CPE.

After a decision to use NI-PPV is made, it should beinstituted as soonaspossible (Figure 7) (55). EitherCPAPorBiPAP is a reasonable first option for the patient with CPE.In the patient with acidosis, hypercapnia, or concomitantCOPD, BiPAP is preferred as the initial modality. If NI-PPVis going to be successful, the patient will generally showimprovement in respiratory and heart rate, work-of-breathing, and gas exchange in w60 min (56). If the pa-tient continues to deteriorate, intubation should imme-diately be considered.

IM-PPV IN THE PATIENT WITH LEFT HEART FAILURE

AND CARDIOGENIC SHOCK. Up to 80% of patientspresenting with cardiogenic shock (57–59) developrespiratory failure. As described already in thisreview (see the “Pulmonary Mechanics of PPV” sec-tion), IM-PPV with PEEP has favorable effects onhemodynamics in patients with HF (Table 2). Theseeffects include decreasing LV afterload by loweringtransthoracic and transpulmonary pressure (60);improving congestion and unloading the LV bydecreasing preload (61); optimizing LV and RVmyocardial perfusion and relieving ischemia byproviding better oxygenation, reversing hypoxicpulmonary vasoconstriction, and decreasing work-of-breathing; and improving LV geometry and relatedfunctional MR (18,19,62). Through these effects onpreload and afterload, PEEP improves alveolar andinterstitial edema. An example algorithm for imple-mentation of IM-PPV in patients with heart failure orshock is shown in Figure 8.

Despite these benefits, there are concerns aboutpotential detrimental effects of PEEP in patientswith LV dysfunction, resulting in decreased CO dueto decreased RV preload and increased afterload(16). However, in vivo studies have not supportedthis concern, especially when RV function andvolume status are normal (63,64). Therefore, inpractice, it appears relevant to differentiate physi-ological effects of PEEP in normal versus failingventricles. The normal LV is preload dependent andmore sensitive to a reduction in venous return withPEEP. In contrast, in patients with a dilated andhypokinetic LV who are afterload-dependent, PEEPwill decrease preload and congestion and will pro-mote forward flow (65). In patients with elevatedpulmonary capillary wedge pressure (PCWP), COimproves as PEEP is increased (from 0 to 8 cmH2O)(66); however, in patients with normal or low pul-monary capillary wedge pressure, PEEP may lowerCO (61,67). Consequently, in patients with purecardiogenic shock with high filling pressures andhigh systemic vascular resistance, PEEP can providebenefit if the RV is not compromised and the pa-tient is not hypovolemic (Figure 8).

IM-PPV IN THE PATIENT WITH RV FAILURE. Themanagement of respiratory failure with IM-PPV inpatients with RV failure is particularly challenging(27). IM-PPV should be avoided when possible or usedcautiously in these patients because of the risk ofadverse hemodynamic effects (68,69). Simultaneousloss of sympathetic tone with sedation, and alveolarde-recruitment due to hypopnea from loss of respi-ratory drive can contribute to a precipitous develop-ment of hypotension for which the clinician mustbe prepared. When endotracheal intubation isnecessary, preload and mean arterial pressure shouldbe optimized before sedating the patient for intuba-tion. After volume optimization, a vasopressor and, ifnecessary, a pulmonary vasodilator should be used tomaintain mean arterial pressure above the meanpulmonary artery pressure (ideally above 60 mm Hg).In addition, it is preferred to consult a cardiac anes-thesiologist for intubation if time permits. Preferredanesthetic agents are those with less negative effectson inotropy and vascular tone, such as ketamine oretomidate (Table 6). However, ketamine should beavoided in patients with poor sympathetic compen-sation as its negative inotropic properties can stillresult in a hypotensive response. Once intubated,ongoing attention to maintain adequate preload iscrucial (20,27).

During IM-PPV in patients with RV failure, lowand high tidal volumes (atelectasis and



1548

overdistention) (Figure 4), high Pplat, hypoxia andhypercarbia (70), as well as high PEEP can all in-crease RV afterload. In RV failure, ventilator strate-gies should aim to achieve alveolar recruitment,while limiting overdistension. Other more specificgoals of IM-PPV in this patient population includeimproving oxygenation, avoiding hypercarbia, and ingeneral using low to moderate tidal volumes (e.g.,w8 ml/kg of ideal body weight), while maintainingPplat <30 cmH20 and minimizing PEEP (initial set-tings of 3 to 5 cmH2O if the patient has cardiogenicshock [64] and <12 cmH2O if the patient is not inshock [71,72]). As acidosis increases PVR, maintain-ing the PaCO2 <60 mmHg will improve PVR, even ifthe etiology of acidosis is metabolic (73) (Figure 8).As an advanced topic, serial evaluation of the pres-sure/volume curves and stress index (the ratio ofrecruitment/hyperinflation of a lung at differentpressure/time points) in the ventilator can assist theclinician to achieve these goals and tailor the IM-PPVstrategy to the patient (74,75).

Advanced approaches to IM-PPV may be consid-ered for some patients with RV failure, includingAPRV, high frequency oscillatory ventilation (HFOV),and prone ventilation (see the “Management of Re-fractory Hypoxemia” section). While the use of proneventilation can improve PVR, RV hemodynamics, andoxygenation (76), the evidence supporting thisapproach, as well as APRV and HFOV, is limited topreclinical studies and small series (17,73,76,77).

OTHER PRELOAD DEPENDENT STATES: TAMPONADE,

CONSTRICTION. Among patients with tamponade,IM-PPV should, in general, be reserved for patientswho become unstable, lose their ability to protecttheir airway, or are having surgical interventions.Because of the preload dependence and compensa-tory tachycardia present in patients with tamponadeand constriction, PPV and associated induction andsedation can precipitate hemodynamic collapse.Therefore, NI-PPV may be preferable, limiting PEEP.Moreover, optimization of preload is important. Inpatients for whom intubation is the only option, anawake-intubation technique may be considered withvasopressors ready and with capacity to performemergent pericardiocentesis or pericardial windowif cardiac collapse occurs. Very low PEEP should beused (0 to 3 cmH2O) to avoid compromising venousreturn, until the pericardial fluid has been evacu-ated (78).

IM-PPV DURING EXTRACORPOREAL LIFE SUPPORT.

Cardiogenic shock is one of the fastest growingindications for ECMO in adults (79). Veno-arterial

ECMO provides both biventricular circulatory andrespiratory support (80). After removal of venousblood via the drainage cannula, deoxygenated bloodpasses through the oxygenator before returning to thearterial system (81).

Gas exchange through ECMO allows the clinician toselect “rest settings” to minimize ventilator-associated lung injury (VALI). Although wide varia-tion in practice exists and clinical guidelines arelimited (82), most experts advocate for low tidalvolumes (4 to 6 ml/kg of ideal body weight), lowrespiratory rates (5 to 10 breaths/min), allowance ofspontaneous breaths if possible, PEEP #10 cmH2O,Pplat <25 cmH20, and the lowest tolerable FiO2 (81,83).Many centers use pressure-control ventilation basedon the protocol from the CESAR (Efficacy and Eco-nomic Assessment of Conventional Ventilatory Sup-port Versus Extracorporeal Membrane Oxygenationfor Severe Adult Respiratory Failure) trial (82,84).However, others advocate for volume-controlledventilation (82). Ventilation strategies in patientsreceiving ECMO remain an important area for futureresearch.

CARDIAC EFFECTS OF SEDATIVES,

NEUROMUSCULAR BLOCKERS, ANALGESICS,

AND ANXIOLYTICS

Practicing cardiologists should be aware of the multiplerelevant cardiovascular effects of many of the pharmaco-therapies necessary for general critical care in the CICU, aswell as the central role of pharmacologicalmanagement ofpain and delirium in effective IM-PPV and successfulextubation. Observational data suggest that participationof a critical care pharmacist in ICU rounds can reduceadverse drug events, prescribing errors, and enhancetherapeutic choices (85,86). Many drugs, including opi-ates, dexmedetomidine, and propofol, can cause hypo-tension and bradycardia through different mechanisms(Table 6). Guidelines for management of pain, agitation,delirium, and neuromuscular blockade are available(87,88).

MANAGEMENT OF REFRACTORY HYPOXEMIA

When patients do not respond to the ventilationstrategies already described, available rescue thera-pies include recruitment maneuvers, advancedventilation strategies, neuromuscular blockade toimprove ventilation synchrony, prone positioning,vasodilators, and ECMO. These strategies have beenstudied predominantly in ARDS; nevertheless, theyare of increasing relevance to the broad spectrum ofpatients cared for in some advanced CICUs.


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Dependent lung regions are perfused but may haveinadequate aeration. Lung recruitment maneuversare based on transiently increasing PEEP to higherthan normal to improve oxygenation and reduceVALI. Although early clinical trials and a meta-analysis indicated no harm from recruitment ma-neuvers, a recent clinical trial suggested that lungrecruitment maneuvers and progressive PEEP titra-tion may be associated with harm (13,89–91).

Survival data for other ventilatory modes such asHFOV or APRV are lacking. HFOV improves oxygen-ation, but does not improve survival and was associ-ated with harm in one trial (92–94).

In a clinical trial of 340 subjects, neuromuscularblockade for 48 h prevented patient-ventilator dys-synchrony and lung injury, and reduced 90-daymortality (95). Although delirium and critical illnessneuromyopathy are concerns, short-term use ofneuromuscular blockade has not been associated withincreased muscle weakness (95). When neuromus-cular blockade is prescribed, sufficient sedation andanalgesia are essential to avoid awareness (87).

Prone positioning has been advocated in severehypoxemia to improve outcomes by lung recruitmentand reduced ventilation-perfusion mismatch. Earlyclinical trials did not demonstrate benefit from a shortduration of proning, but in a subsequent trial, pron-ing for at least 16 h daily reduced mortality (96–98).Proning appears to be more effective if initiatedwithin 3 days of respiratory failure and to be lessuseful after 7 days (99).

Vasodilators, such as inhaled nitric oxide andinhaled epoprostenol, have been used in severehypoxemia to improve ventilation-perfusionmismatch and to reduce pulmonary hypertensionwith transient improvements in oxygenation, but noreduction in mortality. Inhaled pulmonary vasodila-tors can be utilized as rescue therapy for pulmonaryhypertension associated with severe hypoxemia as abridge to other therapies (100–102). However, pul-monary vasodilators may precipitate pulmonaryedema in patients with poor LV performance and highfilling pressures, due to the sudden increase in pul-monary blood flow. Nitric oxide can be associatedwith development of renal dysfunction (103) andmethemoglobinemia (104).

MAJOR COMPLICATIONS OF IM-PPV

Along with avoidance of the deleterious hemody-namic effects of IM-PPV described in the previoustext, the CICU clinician should be aware of otherimportant complications of IM-PPV and strategies to

prevent them. VALI and ventilator-associated pneu-monia (VAP) are frequent and potentially preventablecomplications that are associated with significantmorbidity and mortality.

Although more common in patients with ARDS,VALI has been estimated to occur in >25% of venti-lated patients without ARDS. The most clinicallyrecognized form of VALI is barotrauma (pneumo-thorax and pneumomediastinum), but it also includesvolutrauma, atelectrauma, biotrauma (inflammatoryresponse), and oxygen toxicity (105). Unlike in ARDS,there is not a defined TV goal for critically ill venti-lated patients without lung injury (106). Severalstudies, including meta-analyses, have suggestedthat lower TV is associated with a decreased inci-dence of pulmonary infection, ARDS, and death(106,107). However, these studies are limited by lackof a standard of care control arm. In addition totolerating hypercapnia and lower tidal volumes,avoidance of alveolar overdistension should beattempted with Pplat <30 cmH2O. Minimizing drivingpressure (“delta P”: Pplat – PEEP) (Figure 2) may bemore relevant than low TV to improve outcomes inARDS (108).

However, ventilation at low lung volumes canlead to the continuous recruitment and derecruit-ment of alveolar units resulting in shear stress andatelectrauma (105). Clinically, atelectrauma can bedifficult to detect and often requires assessmentof pressure-volume loops with heavy sedation orneuromuscular blockade (109). Prevention of atelec-trauma is accomplished by PEEP, and in certainclinical scenarios (e.g., perioperative care), by peri-odic recruitment maneuvers, while its role in otherconditions such as ARDS is less clear. Placement of anesophageal balloon to more accurately measuretranspulmonary pressure and lung compliance maybe useful (110).

VAP is associated with a considerable increase inpatient morbidity, mortality, and cost (111). Althoughevidence is limited, the incidence of VAP in the CICUappears to be as high or higher than other ICUs (112).Simple cost-effective measures shown to reduce VAPinclude elevation of the head of the bed >30�, tar-geted sedation, daily spontaneous awakening trialswith or without spontaneous breathing trials (SBT) tominimize ventilator days, proper maintenance ofventilator circuits, and early mobilization (113,114).Incorporating these strategies with oral chlorhexidinehas also reduced VAP (115). Subglottic secretiondrainage may also reduce ICU length of stay andduration of IM-PPV, and increase time to first episodeof VAP (116).

TABLE 7 Key Points

� Positive pressure ventilation decreases RV preload, increases RV afterload, anddecreases LV afterload.

� High-flow oxygen can avoid the need for positive pressure ventilation in some patients.

� BiPAP is preferred over CPAP when there is a need to reduce work of breathing and/orimprove ventilation in patients with hypercarbia.

� PEEP is useful for oxygenation and to avoid or treat atelectasis, but can also be useful inunloading a failing LV.

� Auto-PEEP should be watched for in patients with increased airway resistance, hyperin-flation, or ineffective triggering, and can lead to hemodynamic instability or barotrauma.

� Positive pressure should be avoided if possible, or used cautiously, in conditionsdependent on adequate RV filling, such as acute pulmonary hypertension, RV failure.and tamponade.

BiPAP ¼ bilevel positive airway pressure; CPAP ¼ continuous positive airway pressure; other abbreviations as inTable 1.



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PRINCIPLES OF WEANING FROM IM-PPV

The most effective intervention to reduce compli-cations is early liberation from IM-PPV. Withincreasing IM-PPV duration, complications, mortal-ity, and cost increase (117). However, patients whofail extubation after tolerating SBT show anincreased risk of complications and mortalitycompared with similar patients who were success-fully extubated (118).

IM-PPV and associated analgesics and sedativesoften reduce blood pressure, heart rate, myocardialwork, and oxygen consumption. Liberation from IM-PPV removes these effects and, therefore, can pre-cipitate adverse consequences in cardiac patients,including “weaning-induced pulmonary edema”(119). Professional guidelines for liberation emphasizeSBT with inspiratory pressure augmentation, mini-mized sedation, early mobilization, and extubation ofhigh-risk patients to NI-PPV or HFNC (120,121).

Assessment of readiness for extubation includesdetermining if the precipitating cause of respiratoryfailure has been sufficiently mitigated, electrical orhemodynamic stability is present, and the patient cancooperate. Second, an SBT can be attempted withpressure support (e.g., 5 cmH20) to overcome endo-tracheal tube resistance, and is generally preferredover T-piece or CPAP alone. Although a successfulSBT with T-piece or CPAP alone might predict extu-bation success, this strategy can increase myocardialoxygen consumption and may be best avoided inpatients with compromised ventricular function,ischemic heart disease, or in scenarios where after-load increases are detrimental (e.g., severe valvularregurgitation) (44,122). Predictors of successfulextubation, such as a rapid shallow breathing index(respiratory rate/TV in liters) #105, a negative

inspiratory force <�30 cmH2O, a strong cough, or thepresence of a cuff leak, are all imperfect but cansupplement the general clinical assessment (123).

Failure to liberate from IM-PPV should triggersuspicion for weaning-induced pulmonary edema(124). Consideration should be given to persistentvolume overload, myocardial ischemia, diastolicdysfunction, or mitral regurgitation. Preload, ino-tropy, and afterload optimization can be successfulin managing this problem. Finally, it is important toconsider timing of extubation relative to removal ofmechanical support, particularly for femoral access,so the head of the bead can be elevated during theimmediate post-extubation period to facilitate pul-monary mechanics, improve mobilization of secre-tions, and avoid aspiration events.

Among patients passing SBTs but with a high risk ofextubation failure, NI-PPV and HFNC offer options toimprove success in the post-extubation period. In-dicators of high risk of failure are common in the CICUpopulation: age >65 years, morbid obesity (body massindex $35 kg/m2), heart failure, and a history of othercardiac comorbidities (125,126). The American Collegeof Chest Physicians and the American Thoracic Societyguidelines give post-extubation NI-PPV a “strongrecommendation” in high-risk patients (125). If thisstrategy is taken, NI-PPV should be applied immedi-ately following extubation. Applying NI-PPV afterdevelopment of post-extubation respiratory failuremay be detrimental by delaying reintubation (127).

CONCLUSIONS

Cardiologists who practice in the CICU should befamiliar with the effects of PPV on cardiopulmonaryphysiology so that ventilator management can betailored to optimize hemodynamics, oxygenation,and ventilation (Table 7). As critical care cardiologycontinues to evolve, dedicated ventilation manage-ment studies in the CICU are of heightened impor-tance to achieve this goal.

ACKNOWLEDGMENTS The authors are grateful forthe support of the Heart Failure and Cardiac Trans-plant Council, Sarah Sears, and Alicia McClarin of theAmerican College of Cardiology.

ADDRESS FOR CORRESPONDENCE: Dr. David A.Morrow, Levine Cardiac Intensive Care Unit, Cardio-vascular Division, Department of Medicine, Brighamand Women’s Hospital, 75 Francis Street, Boston,Massachusetts 02115. E-mail: [email protected]. Twitter: @BrighamWomens.

mailto:[email protected]

mailto:[email protected]

https://twitter.com/BrighamWomens


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KEY WORDS coronary intensive care unit,heart failure, mechanical ventilation,noninvasive ventilation, pulmonary edema,respiratory failure

APPENDIX For supplemental figures andtables, please see the online version of thispaper.



















































































































































































positive pressure ventilation in the cardiac intensive ... · including noninvasive positive...

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