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Courtesy of L E K A R SPECIAL EDITIONAuthors: Marino, Paul L.Title: ICU Book, The, 3rd EditionCopyright ©2007 Lippincott Williams & WilkinsISBN: 0-7817-4802-X
Table of ContentsSection I - Basic Science ReviewBasic Science ReviewChapter 1 - Circulatory Blood FlowChapter 2 - Oxygen and Carbon Dioxide TransportSection II - Preventive Practices in the Critically IllPreventive Practices in the Critically IllChapter 3 - Infection Control in the ICUChapter 4 - Alimentary ProphylaxisChapter 5 - Venous ThromboembolismSection III - Vascular AccessVascular AccessChapter 6 - Establishing Venous AccessChapter 7 - The Indwelling Vascular CatheterSection IV - Hemodynamic MonitoringHemodynamic MonitoringChapter 8 - Arterial Blood PressureChapter 9 - The Pulmonary Artery CatheterChapter 10 - Central Venous Pressure and Wedge PressureChapter 11 - Tissue OxygenationSection V - Disorders of Circulatory FlowDisorders of Circulatory FlowChapter 12 - Hemorrhage and HypovolemiaChapter 13 - Colloid and Crystalloid ResuscitationChapter 14 - Acute Heart Failure Syndromes
Chapter 15 - Cardiac ArrestChapter 16 - Hemodynamic Drug InfusionsSection VI - Critical Care CardiologyCritical Care CardiologyChapter 17 - Early Management of Acute Coronary SyndromesChapter 18 - TachyarrhythmiasSection VII - Acute Respiratory FailureAcute Respiratory FailureChapter 19 - Hypoxemia and HypercapniaChapter 20 - Oximetry and CapnographyChapter 21 - Oxygen Inhalation TherapyChapter 22 - Acute Respiratory Distress SyndromeChapter 23 - Severe Airflow ObstructionSection VIII - Mechanical VentilationMechanical VentilationChapter 24 - Principles of Mechanical VentilationChapter 25 - Modes of Assisted VentilationChapter 26 - The Ventilator-Dependent PatientChapter 27 - Discontinuing Mechanical VentilationSection IX - Acid-Base DisordersAcid-Base DisordersChapter 28 - Acid-Base InterpretationsChapter 29 - Organic AcidosesChapter 30 - Metabolic AlkalosisSection X - Renal and Electrolyte DisordersRenal and Electrolyte DisordersChapter 31 - Oliguria and Acute Renal Failure
Chapter 32 - Hypertonic and Hypotonic ConditionsChapter 33 - PotassiumChapter 34 - MagnesiumChapter 35 - Calcium and PhosphorusSection XI - Transfusion Practices in Critical CareTransfusion Practices in Critical CareChapter 36 - Anemia and Red Blood Cell Transfusions in the ICUChapter 37 - Platelets in Critical IllnessSection XII - Disorders of Body TemperatureDisorders of Body TemperatureChapter 38 - Hyperthermia and Hypothermia SyndromesChapter 39 - Fever in the ICUSection XIII - Inflammation and Infection in the ICUInflammation and Infection in the ICUChapter 40 - Infection, Inflammation, and Multiorgan InjuryChapter 41 - Pneumonia in the ICUChapter 42 - Sepsis from the Abdomen and PelvisChapter 43 - The Immuno-Compromised PatientChapter 44 - Antimicrobial TherapySection XIV - Nutrition and MetabolismNutrition and MetabolismChapter 45 - Metabolic Substrate RequirementsChapter 46 - Enteral Tube FeedingChapter 47 - Parenteral NutritionChapter 48 - Adrenal and Thyroid DysfunctionSection XV - Critical Care NeurologyCritical Care Neurology
Chapter 49 - Analgesia and SedationChapter 50 - Disorders of MentationChapter 51 - Disorders of MovementChapter 52 - Stroke and Related DisordersSection XVI - Toxic IngestionsToxic IngestionsChapter 53 - Pharmaceutical Toxins & AntidotesSection XVII: AppendicesAppendix 1 - Units and ConversionsAppendix 2 - Selected Reference RangesAppendix 3 - Clinical Scoring Systems
AuthorPaul L. Marino MD, PhD, FCCMPhysician-in-ChiefSaint Vincents Midtown Hospital, New York, New York; Clinical Associate Professor,New York Medical College, Valhalla, New YorkContributorKenneth M. Sutin MD, FCCMDr. Kenneth Sutin contributed to the final 13 chapters of this bookDepartment of Anesthesiology, Bellevue Hospital Center; Associate Professor ofAnesthesiology & Surgery, New York University School of Medicine, New York, New YorkIllustratorPatricia GastSecondary EditorsBrian BrownAcquisitions EditorNicole DernoskiManaging EditorTanya LazarManaging EditorBridgett DoughertyProduction ManagerBenjamin RiveraSenior Manufacturing ManagerAngela PanettaMarketing ManagerDoug SmockCreative DirectorNesbitt Graphics, Inc.Production ServicesRR Donnelley
PrinterCopyright (c) 2000-2006 Ovid Technologies, Inc.Version: rel10.3.2, SourceID 1.12052.1.159
DedicationTo Daniel Joseph Marino, My 18-year-old son. No longer a boy, And not yet a man, Butalways terrific.Copyright (c) 2000-2006 Ovid Technologies, Inc.Version: rel10.3.2, SourceID 1.12052.1.159
Quote I would especially commend the physician who, in acute diseases, by which the bulk of mankind are cutoff, conducts the treatment better than others. —HIPPOCRATESCopyright (c) 2000-2006 Ovid Technologies, Inc.Version: rel10.3.2, SourceID 1.12052.1.159
Preface to Third EditionThe third edition of The ICU Book marks its 15 th year as a fundamental sourcebook incritical care. This edition continues the original intent to provide a generic textbook thatpresents fundamental concepts and patient care practices that can be used in anyintensive care unit, regardless of the specialty focus of the unit. Highly specialized areas,such as obstetrical emergencies, thermal injury, and neurocritical care, are left to morequalified authors and their specialty textbooks.Most of the chapters in this edition have been completely rewritten (including 198 newillustrations and 178 new tables), and there are two new chapters on infection control inthe ICU (Chapter 3) and disorders of temperature regulation (Chapter 38). Most chaptersalso include a final section (called A Final Word) that contains an important take-homemessage from the chapter. The references have been extensively updated, withemphasis on recent reviews and clinical practice guidelines.The ICU Book has been unique in that it reflects the voice of one author. This editionwelcomes the voice of another, Dr. Kenneth Sutin, who added his expertise to the final 13chapters of the book. Ken and I are old friends who share the same view of critical caremedicine, and his contributions add a robust quality to the material without changing thebasic personality of the work.Copyright (c) 2000-2006 Ovid Technologies, Inc.Version: rel10.3.2, SourceID 1.12052.1.159
Preface to First EditionIn recent years, the trend has been away from a unified approach to critical illness, as thespecialty of critical care becomes a hyphenated attachment for other specialties to use asa territorial signpost. The landlord system has created a disorganized array of intensivecare units (10 different varieties at last count), each acting with little communion.However, the daily concerns in each intensive care unit are remarkably similar becauseserious illness has no landlord. The purpose of The ICU Book is to present this commonground in critical care and to focus on the fundamental principles of critical illness ratherthan the specific interests for each intensive care unit. As the title indicates, this is a‘generic’ text for all intensive care units, regardless of the name on the door.The present text differs from others in the field in that it is neither panoramic in scope noroverly indulgent in any one area. Much of the information originates from a decade ofpractice in intensive care units, the last three years in both a Medical ICU and a SurgicalICU. Daily rounds with both surgical and medical housestaff have provided the foundationfor the concept of generic critical care that is the theme of this book.As indicated in the chapter headings, this text is problem-oriented rather thandisease-oriented, and each problem is presented through the eyes of the ICU physician.Instead of a chapter on GI bleeding, there is a chapter of the principles of volumeresuscitation and two others on resuscitation fluids. This mimics the actual role of the ICUphysician in GI bleeding, which is to manage the hemorrhage. The other features of theproblem such as locating the bleeding site, are the tasks of other specialists. This is howthe ICU operates and this is the specialty of critical care. Highly specialized topics suchas burns, head trauma, and obstetric emergencies are not covered in this text. These aredistinct subspecialties with their own texts and their own experts, and devoting a fewpages to each would merely complete and outline rather than instruct.The emphasis on fundamentals in The ICU Book is meant not only as a foundation forpatient care but also to develop a strong base in clinical problem solving for any area ofmedicine. There is a tendency to rush past the basics in the stampede to finish formaltraining, and this leads to empiricism and irrational practice habits. Why a fever should orshould not be treated, or whether a blood pressure cuff provides accurate readings, arequestions that must be dissected carefully in the early stages of training, to develop thereasoning skills needed to be effective in clinical problems solving. This inquisitive staremust replace the knee-jerk approach to clinical problems if medicine is to advance. TheICU Book helps to develop this stare.Wisely or not, the use of a single author was guided by the desire to present a uniformview. Much of the information is accompanied by published works listed at the end ofeach chapter and anecdotal tales are held to a minimum. Within an endeavor such asthis, several shortcomings are inevitable, some omissions are likely and bias mayoccasionally replace sound judgment. The hope is that these deficiencies are few.Copyright (c) 2000-2006 Ovid Technologies, Inc.Version: rel10.3.2, SourceID 1.12052.1.159
AcknowledgmentsAcknowledgements are few but well deserved. First to Patricia Gast, the illustrator for thisedition, who was involved in every facet of this work, and who added an energy andintelligence that goes well beyond the contributions of medical illustrators. Also to TanyaLazar and Nicole Dernoski, my editors, for understanding the enormous timecommittment required to complete a work of this kind. And finally to the members of theexecutive and medical staff of my hospital, as well as my personal staff, who allowed methe time and intellectual space to complete this work unencumbered by the daily (andsometimes hourly) tasks involved in keeping the doors of a hospital open.Copyright (c) 2000-2006 Ovid Technologies, Inc.Version: rel10.3.2, SourceID 1.12052.1.159
Basic Science Review The first step in applying the scientific method consists in being curious about the world. --Linus Pauling
Chapter 1Circulatory Blood Flow When is a piece of matter said to be alive? When it goes on “doing something,” moving, exchanging material with its environment. --Erwin SchrodingerThe human organism has an estimated 100 trillion cells that must go on exchangingmaterial with the external environment to stay alive. This exchange is made possible by acirculatory system that uses a muscular pump (the heart), an exchange fluid (blood), anda network of conduits (blood vessels). Each day, the human heart pumps about 8,000liters of blood through a vascular network that stretches more than 60,000 miles (morethan twice the circumference of the Earth!) to maintain cellular exchange (1).This chapter describes the forces responsible for the flow of blood though the humancirculatory system. The first half is devoted to the determinants of cardiac output, and thesecond half describes the forces that influence peripheral blood flow. Most of theconcepts in this chapter are old friends from the physiology classroom.Cardiac OutputCirculatory flow originates in the muscular contractions of the heart. Since blood is anincompressible fluid that flows through a closed hydraulic loop, the volume of bloodejected by the left side of the heart must equal the volume of blood returning to the rightside of the heart (over a given time period). This conservation of mass (volume) in aclosed hydraulic system is known as the principle of continuity (2), and it indicates thatthe stroke output of the heart is the principal determinant of circulatory blood flow. Theforces that govern cardiac stroke output are identified in Table 1.1. TABLE 1.1 The Forces that Determine Cardiac Stroke Output
Force Definition Clinical Parameters Preload The load imposed on resting End-diastolic pressure muscle that stretches the muscle to a new length Contractility The velocity of muscle Cardiac stroke volume contraction when muscle when preload and load is fixed afterload are constant Afterload The total load that must be Pulmonary and systemic moved by a muscle when it vascular resistances contractsP.4PreloadIf one end of a muscle fiber is suspended from a rigid strut and a weight is attached to theother free end, the added weight will stretch the muscle to a new length. The addedweight in this situation represents a force called the preload, which is a force imposed ona resting muscle (prior to the onset of muscle contraction) that stretches the muscle to anew length. According to the length–tension relationship of muscle, an increase in thelength of a resting (unstimulated) muscle will increase the force of contraction when themuscle is stimulated to contract. Therefore the preload force acts to augment theforce of muscle contraction.In the intact heart, the stretch imposed on the cardiac muscle prior to the onset of musclecontraction is a function of the volume in the ventricles at the end of diastole. Thereforethe end-diastolic volume of the ventricles is the preload force of the intact heart (3).Preload and Systolic PerformanceThe pressure-volume curves in Figure 1.1 show the influence of diastolic volume on thesystolic performance of the heart. As the ventricle fills during diastole, there is anincrease in both diastolic and systolic pressures. The increase in diastolic pressure is areflection of the passive stretch imposed on the ventricle, while the difference betweendiastolic and systolic pressures is a reflection of the strength of ventricular contraction.Note that as diastolic volume increases, there is an increase in the difference betweendiastolic and systolic pressures, indicating that the strength of ventricular contraction isincreasing. The importance of preload in augmenting cardiac contraction was discoveredindependently by Otto Frank (a German engineer) and Ernest Starling (a Britishphysiologist), and their discovery is commonly referred to as the Frank-Starlingrelationship of the heart (3). This relationship can be stated as follows: In the normalheart, diastolic volume is the principal force that governs the strength of
ventricular contraction (3).Clinical MonitoringIn the clinical setting, the relationship between preload and systolic performance ismonitored with ventricular function curves like the ones P.5shown in Figure 1.2. End-diastolic pressure (EDP) is used as the clinical measure ofpreload because end-diastolic volume is not easily measured (the measurement of EDPis described in Chapter 10). The normal ventricular function curve has a steep ascent,indicating that changes in preload have a marked influence on systolic performance in thenormal heart (i.e., the Frank-Starling relationship). When myocardial contractility isreduced, there is a decrease in the slope of the curve, resulting in an increase inend-diastolic pressure and a decrease in stroke volume. This is the hemodynamic patternseen in patients with heart failure. Figure 1.1 Pressure-volume curves showing the influence of diastolic volume on the strength of ventricular contraction. View FigureVentricular function curves are used frequently in the intensive care unit (ICU) to evaluatepatients who are hemodynamically unstable. However, these curves can be misleading.The major problem is that conditions other than myocardial contractility can influence theslope of these curves. These conditions (i.e., ventricular compliance and ventricularafterload) are described next.Preload and Ventricular ComplianceThe stretch imposed on cardiac muscle is determined not only by the volume of blood inthe ventricles, but also by the tendency of the ventricular wall to distend or stretch inresponse to ventricular filling. P.6The distensibility of the ventricles is referred to as compliance and can be derived usingthe following relationship between changes in end-diastolic pressure (EDP) andend-diastolic volume (EDV) (5):
Figure 1.2 Ventricular function curves used to describe the relationship between preload (end-diastolic pressure) and systolic performance (stroke volume). View FigureThe pressure-volume curves in Figure 1.3 illustrate the influence of ventricularcompliance on the relationship between ?EDP and ?EDV. As compliance decreases (i.e.,as the ventricle becomes stiff), the slope of the curve decreases, resulting in a decreasein EDV at any given EDP. In this situation, the EDP will overestimate the actual preload(EDV). This illustrates how changes in ventricular compliance will influence the reliabilityof EDP as a reflection of preload. The following statements highlight the importance ofventricular compliance in the interpretation of the EDP measurement. 1. End-diastolic pressure is an accurate reflection of preload only when ventricular compliance is normal. 2. Changes in end-diastolic pressure accurately reflect changes in preload only when ventricular compliance is constant.Several conditions can produce a decrease in ventricular compliance. The most commonare left ventricular hypertrophy and ischemic heart P.7disease. Since these conditions are also commonplace in ICU patients, the reliability ofthe EDP measurement is a frequent concern.
Figure 1.3 Diastolic pressure-volume curves in the normal and noncompliant (stiff) ventricle. View FigureDiastolic Heart FailureAs ventricular compliance begins to decrease (e.g., in the early stages of ventricularhypertrophy), the EDP rises, but the EDV remains unchanged. The increase in EDPreduces the pressure gradient for venous inflow into the heart, and this eventually leadsto a decrease in EDV and a resultant decrease in cardiac output (via the Frank-Starlingmechanism). This condition is depicted by the point on the lower graph in Figure 1.3, andis called diastolic heart failure (6). Systolic function (contractile strength) is preserved inthis type of heart failure.Diastolic heart failure should be distinguished from conventional (systolic) heart failurebecause the management of the two conditions differs markedly. For example, sinceventricular filling volumes are reduced in diastolic heart failure, diuretic therapy can becounterproductive. Unfortunately, it is not possible to distinguish between the two types ofheart failure when the EDP is used as a measure of preload because the EDP is elevatedin both conditions. The ventricular function curves in Figure 1.3 illustrate this problem.The point on the lower curve identifies a condition where EDP is elevated and strokevolume is reduced. This condition is often assumed to represent heart failure due tosystolic dysfunction, but diastolic dysfunction would also produce the same changes. Thisinability to distinguish between systolic and diastolic heart failure is one of the majorshortcomings of ventricular function curves. (See Chapter 14 for a more detaileddiscussion of systolic and diastolic heart failure.)P.8AfterloadWhen a weight is attached to one end of a contracting muscle, the force of musclecontraction must overcome the opposing force of the weight before the muscle begins toshorten. The weight in this situation represents a force called the afterload, which isdefined as the load imposed on a muscle after the onset of muscle contraction. Unlike thepreload force, which facilitates muscle contraction, the afterload force opposes musclecontraction (i.e., as the afterload increases, the muscle must develop more tension tomove the load). In the intact heart, the afterload force is equivalent to the peaktension developed across the wall of the ventricles during systole (3).The determinants of ventricular wall tension (afterload) were derived from observationson soap bubbles made by the Marquis de Laplace in 1820. His observations are
expressed in the Law of Laplace, which states that the tension (T) in a thin-walled sphereis directly related to the chamber pressure (P) and radius (r) of the sphere: T = Pr. Whenthe LaPlace relationship is applied to the heart, T represents the peak systolic transmuralwall tension of the ventricle, P represents the transmural pressure across the ventricle atthe end of systole, and r represents the chamber radius at the end of diastole ( 5).The forces that contribute to ventricular afterload can be identified using the componentsof the Laplace relationship, as shown in Figure 1.4. There are three major contributingforces: pleural pressure, arterial impedance, and end-diastolic volume (preload). Preloadis a component of afterload because it is a volume load that must be moved by theventricle during systole. Figure 1.4 The forces that contribute to ventricular afterload. View FigureP.9Pleural PressureSince afterload is a transmural force, it is determined in part by the pleural pressure onthe outer surface of the heart. Negative pleural pressures will increase transmuralpressure and increase ventricular afterload, while positive pleural pressures will have theopposite effect. Negative pressures surrounding the heart can impede ventricularemptying by opposing the inward displacement of the ventricular wall during systole (7,8).This effect is responsible for the transient decrease in systolic blood pressure (reflecting adecrease in cardiac stroke volume) that normally occurs during the inspiratory phase ofspontaneous breathing. When the inspiratory drop in systolic pressure is greater than 15mm Hg, the condition is called “pulsus paradoxus” (which is a misnomer, since theresponse is not paradoxical, but is an exaggeration of the normal response).Positive pleural pressures can promote ventricular emptying by facilitating the inwardmovement of the ventricular wall during systole (7,9). This effect is illustrated in Figure1.5. The tracings in this figure show the effect of positive-pressure mechanical ventilationon the arterial blood pressure. When intrathoracic pressure rises during apositive-pressure breath, there is a transient rise in systolic blood pressure (reflecting anincrease in the stroke volume output of the heart). This response indicates that positiveintrathoracic pressure can provide P.10
cardiac support by “unloading” the left ventricle. Although this effect is probably of minorsignificance, positive-pressure mechanical ventilation has been proposed as a possibletherapeutic modality in patients with cardiogenic shock (10). The hemodynamic effects ofmechanical ventilation are discussed in more detail in Chapter 24. Figure 1.5 Respiratory variations in blood pressure during positive-pressure mechanical ventilation. View FigureImpedanceThe principal determinant of ventricular afterload is a hydraulic force known asimpedance that opposes phasic changes in pressure and flow. This force is mostprominent in the large arteries close to the heart, where it acts to oppose the pulsatileoutput of the ventricles. Aortic impedance is the major afterload force for the leftventricle, and pulmonary artery impedance serves the same role for the right ventricle.Impedance is influenced by two other forces: (a) a force that opposes the rate of changein flow, known as compliance, and (b) a force that opposes steady flow, called resistance.Arterial compliance is expressed primarily in the large, elastic arteries, where it plays amajor role in determining vascular impedance. Arterial resistance is expressed primarilyin the smaller peripheral arteries, where the flow is steady and nonpulsatile. Sinceresistance is a force that opposes nonpulsatile flow, while impedance opposes pulsatileflow, arterial resistance may play a minor role in the impedance to ventricularemptying. Arterial resistance can, however, influence pressure and flow events in thelarge, proximal arteries (where impedance is prominent) because it acts as a downstreamresistance for these arteries.Vascular impedance and compliance are complex, dynamic forces that are not easilymeasured (12,13). Vascular resistance, however, can be calculated as described next.Vascular ResistanceThe resistance (R) to flow in a hydraulic circuit is expressed by the relationship betweenthe pressure gradient across the circuit (?P) and the rate of flow (Q) through the circuit:Applying this relationship to the systemic and pulmonary circulations yields the followingequations for systemic vascular resistance (SVR) and pulmonary vascular resistance
(PVR):SAP is the mean systemic arterial pressure, RAP is the mean right atrial pressure, PAP ismean pulmonary artery pressure, LAP is the mean left atrial pressure, and CO is thecardiac output. The SAP is measured with an arterial catheter (see Chapter 8), and therest of the measurements are obtained with a pulmonary artery catheter (see Chapter 9).P.11Clinical MonitoringThere are no accurate measures of ventricular afterload in the clinical setting. TheSVR and PVR are used as clinical measures of afterload, but they are unreliable (14,15).There are two problems with the use of vascular resistance calculations as a reflection ofventricular afterload. First, arterial resistance may contribute little to ventricular afterloadbecause it is a force that opposes nonpulsatile flow, while afterload (impedance) is aforce that opposes pulsatile flow. Second, the SVR and PVR are measures of totalvascular resistance (arterial and venous), which is even less likely to contribute toventricular afterload than arterial resistance. These limitations have led to therecommendation that PVR and SVR be abandoned as clinical measures of afterload (15).Since afterload can influence the slope of ventricular function curves (see Figure 1.2),changes in the slope of these curves are used as indirect evidence of changes inafterload. However, other forces, such as ventricular compliance and myocardialcontractility, can also influence the slope of ventricular function curves, so unless theseother forces are held constant, a change in the slope of a ventricular function curvecannot be used as evidence of a change in afterload.ContractilityThe contraction of striated muscle is attributed to interactions between contractileproteins arranged in parallel rows in the sarcomere. The number of bridges formedbetween adjacent rows of contractile elements determines the contractile state orcontractility of the muscle fiber. The contractile state of a muscle is reflected by the forceand velocity of muscle contraction when loading conditions (i.e., preload and afterload)are held constant (3). The standard measure of contractility is the acceleration rate ofventricular pressure (dP/dt) during isovolumic contraction (the time from the onset ofsystole to the opening of the aortic valve, when preload and afterload are constant). Thiscan be measured during cardiac catheterization.Clinical MonitoringThere are no reliable measures of myocardial contractility in the clinical setting. Therelationship between end-diastolic pressure and stroke volume (see Figure 1.2) is oftenused as a reflection of contractility; however, other conditions (i.e., ventricular complianceand afterload) can influence this relationship. There are echocardiography techniques forevaluating contractility (15,16), but these are very specialized and not used routinely.Peripheral Blood Flow
As mentioned in the introduction to this chapter, there are over 60,000 miles of bloodvessels in the human body! Even if this estimate is off by 10,000 or 20,000 miles, it stillpoints to the incomprehensible vastness of the human circulatory system. The remainderof this chapter will describe the forces that govern flow through this vast network of bloodvessels.P.12A Note of Caution: The forces that govern peripheral blood flow are derived fromobservations on idealized hydraulic circuits where the flow is steady and laminar(streamlined), and the conducting tubes are rigid. These conditions bear littleresemblance to the human circulatory system, where the flow is often pulsatile andturbulent, and the blood vessels are compressible and not rigid. Because of thesedifferences, the description of blood flow that follows should be viewed as a veryschematic representation of what really happens in the circulatory system.Flow in Rigid TubesSteady flow (Q) through a hollow, rigid tube is proportional to the pressure gradient alongthe length of the tube (?P), and the constant of proportionality is the hydraulic resistanceto flow (R):The resistance to flow in small tubes was described independently by a Germanphysiologist (G. Hagen) and a French physician (J. Poisseuille). They found thatresistance to flow is a function of the inner radius of the tube (r), the length of the tube (L),and the viscosity of the fluid (m). Their observations are expressed in the followingequation, known as the Hagen-Poisseuille equation (18):The final term in the equation is the reciprocal of resistance (1/R), so resistance can bedescribed asThe Hagen-Poisseuille equation is illustrated in Figure 1.6. Note that flow variesaccording to the fourth power of the inner radius of the tube. This means that a two-foldincrease in the radius of the tube will result in a sixteen-fold increase in flow: (2r)4 =16r. The other components of resistance (i.e., tube length and fluid viscosity) exert amuch smaller influence on flow.Since the Hagen-Poisseuille equation describes steady flow through rigid tubes, it maynot accurately describe the behavior of the circulatory system (where flow is not steadyand the tubes are not rigid). However, there are several useful applications of thisequation. In Chapter 6, it will be used to describe flow through vascular catheters (seeFigure 6.1). In Chapter 12, it will be used to describe the flow characteristics of differentresuscitation fluids, and in Chapter 36, it will be used to describe the hemodynamiceffects of anemia and blood transfusions.Flow in Tubes of Varying DiameterAs blood moves away from the heart and encounters vessels of decreasing diameter, theresistance to flow should increase and the flow should decrease. This is not possiblebecause (according to the principle of
P.13continuity) blood flow must be the same at all points along the circulatory system. Thisdiscrepancy can be resolved by considering the influence of tube narrowing on flowvelocity. For a rigid tube of varying diameter, the velocity of flow (v) at any point along thetube is directly proportional to the bulk flow (Q), and inversely proportional to thecross-sectional area of the tube: v = Q/A (2). Rearranging terms (and using A = p 2) yieldsthe following: Figure 1.6 The forces that influence steady flow in rigid tubes. Q = flow rate, Pin = inlet pressure, Pout = outlet pressure, µ = viscosity, r = inner radius, L = length. View FigureThis shows that bulk flow can remain unchanged when a tube narrows if there is anappropriate increase in the velocity of flow. This is how the nozzle on a garden hoseworks and is how blood flow remains constant as the blood vessels narrow.Flow in Compressible TubesFlow through compressible tubes (like blood vessels) is influenced by the externalpressure surrounding the tube. This is illustrated in Figure 1.7, which shows acompressible tube running through a fluid reservoir. The height of the fluid in the reservoircan be adjusted to vary the external pressure on the tube. When there is no fluid in thereservoir and the external pressure is zero, the driving force for flow through the tube willbe the pressure gradient between the two ends of the tube (P in - P out). When thereservoir fills and the external pressure exceeds the lowest pressure in the tube (P ext –P out), the tube will be compressed. In this situation, the driving force for flow is thepressure gradient between the inlet pressure and the external pressure (P in - Pext ).Therefore when a tube is compressed by external pressure, the driving force forflow is independent of the pressure gradient along the tube (20).
Figure 1.7 The influence of external pressure on flow through compressible tubes. Pin = inlet pressure, Pout = outlet pressure, Pext = external pressure. View FigureP.14The Pulmonary CirculationVascular compression has been demonstrated in the cerebral, pulmonary, and systemiccirculations. It can be particularly prominent in the pulmonary circulation duringpositive-pressure mechanical ventilation, when alveolar pressure exceeds the hydrostaticpressure in the pulmonary capillaries (20). When this occurs, the driving force for flowthrough the lungs is no longer the pressure gradient from the main pulmonary arteries tothe left atrium (PAP - LAP), but instead is the pressure difference between the pulmonaryartery pressure and the alveolar pressure (PAP - Palv). This change in driving pressurenot only contributes to a reduction in pulmonary blood flow, but it also affects thepulmonary vascular resistance (PVR) calculation as follows:Vascular compression in the lungs is discussed again in Chapter 10 (the measurement ofvascular pressures in the thorax) and in Chapter 24 (the hemodynamic effects ofmechanical ventilation).Blood ViscosityA solid will resist being deformed (changing shape), while a fluid will deform continuously(flow) but will resist changes in the rate of deformation (i.e., changes in flow rate) (21).The resistance of a fluid to P.15changes in flow rate is a property known as viscosity (21,22,23). Viscosity has also beenreferred to as the “gooiness” of a fluid (21). When the viscosity of a fluid increases, agreater force must be applied to the fluid to initiate a change in flow rate. The influence ofviscosity on flow rate is apparent to anyone who has poured molasses (high viscosity)and water (low viscosity) from a container.HematocritThe viscosity of whole blood is almost entirely due to cross-linking of circulatingerythrocytes by plasma fibrinogen (22,23). The principal determinant of whole blood
viscosity is the concentration of circulating erythrocytes (the hematocrit). Theinfluence of hematocrit on blood viscosity is shown in Table 1.2. Note that blood viscositycan be expressed in absolute or relative terms (relative to water). In the absence of bloodcells (zero hematocrit), the viscosity of blood (plasma) is only slightly higher than that ofwater. This is not surprising, since plasma is 92% water. At a normal hematocrit (45%),blood viscosity is three times the viscosity of plasma. Thus plasma flows much moreeasily than whole blood, and anemic blood flows much more easily than normal blood.The influence of hematocrit on blood viscosity is the single most important factor thatdetermines the hemodynamic effects of anemia and blood transfusions (see later).Shear ThinningThe viscosity of some fluids varies inversely with a change in flow velocity (21,23). Bloodis one of these fluids. (Another is ketchup, which is thick and difficult to get out of thebottle, but once it starts to flow, it thins out and flows more easily.) Since the velocity ofblood flow increases as the blood vessels narrow, the viscosity of blood will alsodecrease as the P.16blood moves into the small blood vessels in the periphery. The decrease in viscosityoccurs because the velocity of plasma increases more than the velocity of erythrocytes,so the relative plasma volume increases in small blood vessels. This process is calledshear thinning (shear is a tangential force that influences flow rate), and it facilitates flowthrough small vessels. It becomes evident in blood vessels with diameters less than 0.3mm (24). TABLE 1.2 Blood Viscosity as a Function of Hematocrit
Hematocrit Viscosity* Relative Absolute 0 1.4 10 1.8 1.2 20 2.1 1.5 30 2.8 1.8 40 3.7 2.3 50 4.8 2.9 60 5.8 3.8 70 8.2 5.3 * Absolute viscosity expressed in centipoise (cP). Data from Documenta Geigy Scientific Tables. 7th ed. Basel: Documenta Geigy, 1966:557–558.Hemodynamic EffectsThe Hagen-Poisseuille equation indicates that blood flow is inversely related to bloodviscosity, and further that blood flow will change in proportion to a change in viscosity(i.e., if blood viscosity is doubled, blood flow will be halved) (22). The effect of changes inblood viscosity on blood flow is shown in Figure 1.8. In this case, changes in hematocritare used to represent changes in blood viscosity. The data in this graph is from a patientwith polycythemia who was treated with a combination of phlebotomy and fluid infusion(isovolemic hemodilution) to achieve a therapeutic reduction in hematocrit and bloodviscosity. The progressive decrease in hematocrit is associated with a steady rise incardiac output, and the change in cardiac output is far greater than the change inhematocrit. The disproportionate increase in cardiac output is more than expected fromthe Hagen-Poisseuille equation and may be due in part P.17to the fact that blood viscosity varies inversely with flow rate. That is, as viscositydecreases and flow rate increases, the increase in flow rate will cause a further reduction
in viscosity, which will then lead to a further increase in flow rate, and so on. This processwould then magnify the influence of blood viscosity on blood flow. Whether or not this isthe case, the graph in Figure 1.8 demonstrates that changes in hematocrit have aprofound influence on circulatory blood flow. This topic is presented in more detail inChapter 36. Figure 1.8 The influence of progressive hemodilution on cardiac output in a patient with polycythemia. CO = cardiac output. (From LeVeen HH, Ip M, Ahmed N, et al. Lowering blood viscosity to overcome vascular resistance. Surg Gynecol Obstet 1980;150:139.Bibliographic Links) View FigureClinical MonitoringViscosity can be measured with an instrument called (what else?) a viscometer. Thisdevice has two parallel plates: one fixed and one that can move over the surface of thefixed plate. A fluid sample is placed between the two plates, and a force is applied tomove the moveable plate. The force needed to move the plate is proportional to theviscosity of the fluid between the plates. Viscosity is expressed as force per area (surfacearea of the plates). The units of measurement are the “poise” (or dyne · sec/cm 2) in theCGS system, and the “Pascal · second” (Pa · s) in the SI system. (A poise is one/tenth ofa Pascal · second.) Viscosity is also expressed as the ratio of the test sample viscosity tothe viscosity of water. This “relative viscosity” is easier to interpret.Viscosity is rarely measured in the clinical setting. The main reason for this is theconsensus view that in vitro viscosity measurements are unreliable because they do nottake into account conditions in the circulatory system (like shear thinning) that influenceviscosity (21,22,23,24). Monitoring changes in viscosity may be more useful than singlemeasurements. For example, serial changes in blood viscosity could be used to monitorthe effects of aggressive diuretic therapy (e.g., a rise in viscosity to abnormally high levelsmight trigger a reduction in diuretic dosage). The value of blood viscosity measurementsis underappreciated at the present time.ReferencesGeneral Texts
Berne R, Levy M. Cardiovascular physiology, 8th ed. St. Louis: Mosby, 2001. Guyton AC, Jones CE, Coleman TG. Circulatory physiology: cardiac output and its regulation, 2nd ed. Philadelphia: WB Saunders, 1973. Nichols WW, ORourke M. McDonalds blood flow in arteries, 3rd ed. Baltimore: Williams & Wilkins, 1990. Vogel S. Vital circuits. New York: Oxford University Press, 1992. Warltier DC. Ventricular function. Baltimore: Williams & Wilkins, 1995.Cardiac Output 1. Vogel S. Vital circuits. New York: Oxford University Press, 1992:1–17. 2. Vogel S. Life in moving fluids. Princeton: Princeton University Press, 1981: 25–28.P.18 3. Opie LH. Mechanisms of cardiac contraction and relaxation. In: Braunwald E, Zipes DP, Libby P, eds. Heart disease: a textbook of cardiovascular medicine, 6th ed. Philadelphia: WB Saunders, 2001:443–478. 4. Parmley WM, Talbot L. The heart as a pump. In: Berne RM, ed. Handbook of physiology: the cardiovascular system. Bethesda: American Physiological Society, 1979:429–460. 5. Gilbert JC, Glantz SA. Determinants of left ventricular filling and of the diastolic pressure-volume relation. Circ Res 1989;64:827–852. Ovid Full TextBibliographic Links 6. Zile M, Baicu C, Gaasch W. Diastolic heart failure: abnormalities in active relaxation and passive stiffness of the left ventricle. N Engl J Med 2004;350: 1953–1959. Ovid Full TextBibliographic Links 7. Pinsky MR. Cardiopulmonary interactions: the effects of negative and positive changes in pleural pressures on cardiac output. In: Dantzger DR, ed. Cardiopulmonary critical care, 2nd ed. Philadelphia: WB Saunders, 1991: 87–120.
8. Hausnecht N, Brin K, Weisfeldt M, et al. Effects of left ventricular loading by negative intrathoracic pressure in dogs. Circ Res 1988;62:620–631. Ovid Full TextBibliographic Links 9. Magder S. Clinical usefulness of respiratory variations in blood pressure. Am J Respir Crit Care Med 2004;169:151–155. Full TextBibliographic Links 10. Peters J. Mechanical ventilation with PEEP: a unique therapy for failing hearts. Intens Care Med 1999;25:778–780. Bibliographic Links 11. Nichols WW, ORourke MF. Input impedance as ventricular load. In: McDonalds blood flow in arteries, 3rd ed. Philadelphia: Lea & Febiger, 1990: 330–342. 12. Finkelstein SM, Collins R. Vascular impedance measurement. Progr Cardio-vasc Dis 1982;24:401–418. Full TextBibliographic Links 13. Laskey WK, Parker G, Ferrari VA, et al. Estimation of total systemic arterial compliance in humans. J Appl Physiol 1990;69:112–119. Bibliographic Links 14. Lang RM, Borrow KM, Neumann A, et al. Systemic vascular resistance: an unreliable index of left ventricular afterload. Circulation 1986;74:1114–1123. Ovid Full TextBibliographic Links 15. Pinsky MR. Hemodynamic monitoring in the intensive care unit. Clin Chest Med 2003;24:549–560. Bibliographic Links 16. Bargiggia GS, Bertucci C, Recusani F, et al. A new method for estimating left ventricular dP/dt by continuous wave Doppler echocardiography: validation studies at cardiac catheterization. Circulation 1989;80:1287–1292. Ovid Full TextBibliographic Links 17. Broka S, Dubois P, Jamart J, et al. Effects of acute decrease in afterload on accuracy of Doppler-derived left ventricular rate of pressure rise measurement in anesthetized patients. J Am Soc Echocardiogr 2001;14:1161–1165.Bibliographic LinksPeripheral Blood Flow
18. Chien S, Usami S, Skalak R. Blood flow in small tubes. In: Renkin EM, Michel CC, eds. Handbook of physiology, Section 2: the cardiovascular system. Vol IV: The microcirculation. Bethesda: American Physiological Society, 1984:217–249. 19. Little RC, Little WC. Physiology of the heart and circulation, 4th ed. Chicago: Year Book Publishers, 1989:219–236. 20. Gorback MS. Problems associated with the determination of pulmonary vascular resistance. J Clin Monit 1990;6:118–127. Bibliographic LinksP.19 21. Vogel S. Life in moving fluids. Princeton: Princeton University Press, 1981: 11–24. 22. Merrill EW. Rheology of blood. Physiol Rev 1969;49:863–888. Bibliographic Links 23. Lowe GOD. Blood rheology in vitro and in vivo. Baillieres Clin Hematol 1987;1:597. 24. Berne RM, Levy MN. Cardiovascular physiology, 8th ed. Philadelphia: Mosby, 1992:127–133.
Chapter 2Oxygen and Carbon Dioxide Transport Respiration is thus a process of combustion, in truth very slow, but otherwise exactly like that of charcoal. --Antoine LavoisierThe business of aerobic metabolism is the combustion of nutrient fuels to release energy.This process consumes oxygen and generates carbon dioxide. The business of thecirculatory system is to deliver the oxygen and nutrient fuels to the tissues of the body,and then to remove the carbon dioxide that is generated. The dual role of the circulatorysystem in transporting both oxygen and carbon dioxide is referred to as the respiratoryfunction of blood. The business of this chapter is to describe how this respiratory functionis carried out.Oxygen TransportThe transport of oxygen from the lungs to metabolizing tissues can be described by usingfour clinical parameters: (a) the concentration of oxygen in blood, (b) the delivery rate ofoxygen in arterial blood, (c) the rate of oxygen uptake from capillary blood into thetissues, and (d) the fraction of oxygen in capillary blood that is taken up into the tissues.These four oxygen transport parameters are shown in Table 2.1, along with the equationsused to derive each parameter. Thorough knowledge of these parameters is essential forthe management of critically ill patients.O2 Content in BloodOxygen does not dissolve readily in water (1) and, since plasma is 93% water, aspecialized oxygen-binding molecule (hemoglobin) is needed to P.22facilitate the oxygenation of blood. The concentration of oxygen (O2) in blood, also calledthe O2 content, is the summed contribution of O2 that is bound to hemoglobin and O 2 thatis dissolved in plasma. TABLE 2.1 Oxygen and Carbon Dioxide Transport Parameters
Parameter Symbol Equations Arterial O2 content CaO 2 1.34 × Hb × SaO2 Venous O 2 content CvO2 1.34 × Hb × SvO 2 O2 Delivery DO2 Q × CaO2 O2 Uptake VO2 Q × (CaO2 – CvO2) O2 Extraction ratio O2ER VO2/DO2 CO2 Elimination VCO 2 Q × (CvCO2 - CaCO 2) Respiratory quotient RQ VCO 2/VO2 Abbreviations: Hb = hemoglobin concentration in blood; SaO 2 and SvO 2 = oxygen saturation of hemoglobin (ratio of oxygenated hemoglobin to total hemoglobin) in arterial and mixed venous blood, respectively; Q = cardiac output; CaCO2 = CO2 content in arterial blood; CvCO 2 = CO2 content in mixed venous blood.Hemoglobin-Bound O2The concentration of hemoglobin-bound O 2 (HbO 2) is determined by the variables inEquation 2.1 (2).Hb is the hemoglobin concentration in blood (usually expressed in grams per deciliter,which is grams per 100 mL); 1.34 is the oxygen-binding capacity of hemoglobin(expressed in mL O2 per gram of Hb); and SO2 is the ratio of oxygenated hemoglobin tototal hemoglobin in blood (SO2 = HbO2/total Hb), also called the O2 saturation ofhemoglobin. The HbO2 is expressed in the same units as the Hb concentration (g/dL).Equation 2.1 predicts that, when hemoglobin is fully saturated with O 2 (i.e., when the SO2 = 1), each gram of hemoglobin will bind 1.34 mL oxygen. One gram of hemoglobinnormally binds 1.39 mL oxygen, but a small fraction (3% to 5%) of circulating hemoglobinis present as methemoglobin and carboxyhemoglobin and, since these forms of Hb have
a reduced O2-binding capacity, the lower value of 1.34 mL/g is considered morerepresentative of the O2-binding capacity of the total hemoglobin pool (3).Dissolved O2The concentration of dissolved oxygen in plasma is determined by the solubility of oxygenin water (plasma) and the partial pressure of oxygen (PO 2) in blood. The solubility of O2in water is temperature-dependent (solubility increases slightly as temperaturedecreases). At normal body temperature (37 °C), 0.03 mL of O2 will dissolve in one liter ofwater when the Po2 is 1 mm Hg (4). This is expressed as a solubility coefficient of 0.03mL/L/mm Hg (or 0.003 mL/100 mL/mm Hg). The concentration of P.23dissolved O2 (in mL/dL) (at normal body temperature) is then described by Equation 2.2. TABLE 2.2 Normal Levels of Oxygen in Arterial and Venous Blood* Parameter Arterial Blood Venous Blood PO2 90 mm Hg 40 mm Hg O2 Saturation of Hb 0.98 0.73 Hb-bound O 2 197 mL/L 147 mL/L Dissolved O2 2.7 mL/L 1.2 mL/L Total O2 content 200 mL/L 148 mL/L Blood volume † 1.25 L 3.75 L Volume of O 2 250 mL 555 mL *Values shown are for a body temperature of 37°C and a hemoglobin concentration of 15 g/dL (150 g/L) in blood. †Volume estimates are based on a total blood volume (TBV) of = L, arterial blood volume of 0.25 × TBV, and venous blood volume of 0.75 3 TBV. Abbreviations: Hb, hemoglobin 5 PO2, partial pressure of O2.
This equation reveals the limited solubility of oxygen in plasma. For example, if the Po 2 is100 mm Hg, one liter of blood will contain only 3 mL of dissolved o2.Arterial O2 Content (Cao2)The concentration of O2 in arterial blood (Cao 2) can be defined by combining Equations2.1 and 2.2, by using the So2 and Po2 of arterial blood (Sao 2 and Pao2).The normal concentrations of bound, dissolved, and total O2 in arterial blood are shown inTable 2.2. There are approximately 200 mL oxygen in each liter of arterial blood, and only1.5% (3 mL) is dissolved in the plasma. The oxygen consumption of an average-sizedadult at rest is 250 mL/min, which means that if we were forced to rely solely on thedissolved O2 in plasma, a cardiac output of 89 L/min would be necessary to sustainaerobic metabolism. This emphasizes the importance of hemoglobin in the transport ofoxygen.Venous O2 Content (Cvo2)The concentration of O2 in venous blood (Cvo2) can be calculated in the same fashion asthe Cao2, using the O 2 saturation and Po2 in venous blood (Svo2 and Pvo2).P.24The Svo2 and Pvo2 are best measured in a pooled or “mixed venous” blood sample takenfrom the pulmonary artery (using a pulmonary artery catheter, as described in Chapter 9).As shown in Table 2.2, the normal Svo2 is 73% (0.73), the normal Pvo 2 is 40 mm Hg, andthe normal Cvo2 is approximately 15 mL/dL (150 mL/L).Simplified O2 Content EquationThe concentration of dissolved O 2 in plasma is so small that it is usually eliminated fromthe O2 content equation. The O2 content of blood is then considered equivalent to theHb-bound O 2 fraction (see Equation 2.1).Anemia versus HypoxemiaClinicians often use the arterial Po2 (Pao2) as an indication of how much oxygen is in theblood. However, as indicated in Equation 2.5, the hemoglobin concentration is theprincipal determinant of the oxygen content of b