2015 handbook of ICU therapy 3rd ed

Mowaffaq Almikhlafi MD FRCPC Fellow, Critical Care Western, Schulich School of Medicine and Dentistry, Western University, London Health Sciences Centre, London, Ontario, Canada Osama Al

Handbook of ICU Therapy Third edition

Ian McConachie MB ChB FRCA FRCPC

Associate Professor in the Department of Anesthesia and Perioperative Medicine, Division of Critical Care (Department of Medicine), Western University, London, ON, Canada

It furthers the University’s mission by disseminating knowledge in the pursuit of education, learning and research at the highest international levels of excellence.

www.cambridge.org

Information on this title: www.cambridge.org/9781107641907

© Cambridge University Press 2015

This publication is in copyright Subject to statutory exception and to the provisions of relevant collective licensing agreements,

no reproduction of any part may take place without the written permission of Cambridge University Press.

First published 1998

Second edition 2006

Third edition 2015

Printed in the United Kingdom by TJ International Ltd., Padstow, Cornwall

A catalog record for this publication is available from the British Library Library of Congress Cataloging in Publication data

Handbook of ICU therapy / edited by John Fuller, Jeff Granton, Ian McConachie – Third edition.

p ; cm.

Includes bibliographical references and index.

ISBN 978-1-107-64190-7 (Paperback)

I Fuller, John, 1955-editor II Granton, Jeff, editor.

III McConachie, Ian, editor.

[DNLM: 1 Intensive Care –methods–Handbooks WX 39]

List of contributors vii

Preface to the third edition xiii

Section 1 – Basic principles

1 Oxygen delivery, cardiac function

4 Central venous access 28

Ken Blonde and Robert Arntfield

5 Fluid therapy in ICU 38

Janet Martin, John Fuller and Ian

McConachie

6 Anemia and blood transfusion 53

Shane W English and Lauralyn

Ilya Kagan and Pierre Singer

11 Electrolyte and metabolic acid–base

Harneet Kaur, Julio P Zavala Georffino,Daniel Castro Pereira, Bhupesh Khadka,Joseph Dreier and Clay A Block

12 Principles of IPPV and care of theventilated patient 131

Mohit Bhutani and Ian McConachie

13 Modes of ventilation and ventilatorstrategies 144

Tania Ligori

14 Discontinuing mechanicalventilation 152

Ron Butler

15 Vasoactive drugs 161Daniel H Ovakim

16 Optimizing antimicrobial therapy inthe ICU 173

Stephen Y Liang and Anand Kumar

17 Sedation, analgesia andneuromuscular block 187Brian Pollard

18 Continuous renal replacementtherapy 197

A Ebersohn and Rudi Brits

19 Chronic critical illness 209David Leasa

20 Recognizing and responding to thedeteriorating patient 221

John Kellett, Christian P Subbe andRebecca P Winsett

v

21 ICU rehabilitation 235

Linda Denehy and Sue Berney

22 Palliative care, withholding and

withdrawal of life support in the

intensive care unit 252

Lois Champion and Valerie Schulz

Section 2 – Specific problems

23 The injured patient in the ICU 261

Neil Parry and W Robert Leeper

24 Neurotrauma 277

Ari Ercole, Jessie R Welbourne and

Arun K Gupta

25 Acute coronary syndromes 290

Kala Kathirgamanathan and Jaffer

Syed

26 Heart failure 303

Christopher W White, Darren H Freed,

Shelley R Zieroth and Rohit K Singal

27 Arrhythmias 319

Umjeet Singh Jolly and Jaimie

Manlucu

28 The patient with sepsis 334

Jennifer Vergel Del Dios, Tom

Varughese and Ravi Taneja

29 Acute kidney injury 348

RT Noel Gibney

30 Acute lung injury and ARDS 361

Raj Nichani, MJ Naisbitt and Chris

Clarke

31 The patient with gastrointestinal

Biniam Kidane and Tina Mele

32 The comatose patient: neurologicalaspects 391

G Bryan Young

33 The obstetric patient in the

Carlos Kidel and Alan McGlennan

34 The critically ill asthmatic 416Ian M Ball

35 Endocrine problems in criticalillness 427

Mowaffaq Almikhlafi MD FRCPC

Fellow, Critical Care Western, Schulich

School of Medicine and Dentistry, Western

University, London Health Sciences Centre,

London, Ontario, Canada

Osama Al-muslim MD, MRCP (UK)

Critical Care Consultant, Director of Life

Support Training Center, King Fahad

Specialist Hospital, Dammam, Saudi

Arabia

Robert Arntfield MD FRCPC FCCP FACEP

Assistant Professor, Schulich School of

Medicine and Dentistry, Western

University, Director, Critical Care

Ultrasound, Division of Critical Care

(Department of Medicine), London Health

Sciences Centre and St Joseph’s Healthcare

London, London, Ontario, Canada

Ian M Ball MD DABEM FCCP FRCPC

Assistant Professor, Queen’s University,

Kingston, Department of Emergency

Medicine, Department of Biomedical and

Molecular Sciences, Program in Critical

Care Medicine, Consultant Toxicologist,

Ontario Poison Information, Kingston

General Hospital, Kingston, Ontario,

Canada

Sue Berney PhD PT

Associate Professor, Department of

Physiotherapy, Melbourne School of

Health Sciences, The University of

Melbourne, Parkville, Victoria,

Australia

Mohit Bhutani MD FRCPC FCCP

Associate Professor, Division of Pulmonary

Medicine, Department of Medicine,

University of Alberta, Edmonton, Alberta,

Canada

Clay A Block MDAssociate Professor, Department ofMedicine (Nephrology section), GeiselSchool of Medicine, Dartmouth, NH, USAKen Blonde MD

Critical Care Fellow, Faculty of Medicine,University of Calgary, Calgary, Alberta,Canada

Rudi Brits MB ChB FRCA FICMConsultant Anaesthetist, TygerbergHospital, Cape Town, South AfricaRon Butler MD FRCPC

Associate Professor, Department ofAnesthesia and Perioperative Medicine andDivision of Critical Care (Department ofMedicine), Schulich School of Medicineand Dentistry, Western University, LondonHealth Sciences Centre and St Joseph’sHealthcare London, London, Ontario,Canada

Lois Champion MD FRCPCProfessor, Department of Anesthesia andPerioperative Medicine and Division ofCritical Care (Department of Medicine),Schulich School of Medicine and Dentistry,Western University, London HealthSciences Centre and St Joseph’s HealthcareLondon, London, Ontario, Canada

Chris Clarke FRCAConsultant in Anaesthesia and CriticalCare, Blackpool Teaching Hospitals NHSFoundation Trust, Blackpool, UKLinda Denehy PhD PT

Professor and Head, Department ofPhysiotherapy, Melbourne School ofHealth Sciences, The University ofMelbourne, Parkville, Victoria, Australia

vii

Joseph Dreier MD

Department of Medicine (Nephrology

section), Geisel School of Medicine,

Dartmouth, NH, USA

A Ebersohn MB ChB, DA, Dip Obs

Department of Anaesthesia, Tygerberg

Hospital, Cape Town, South Africa

Shane W English BSc MSc MD FRCPC

Assistant Professor, Dept of Medicine

(Critical Care), University of Ottawa,

Clinical Associate, Dept of Critical Care,

The Ottawa Hospital, Associate Scientist,

Ottawa Hospital Research Institute, Centre

for Transfusion Research, Clinical

Epidemiology Program, Ottawa, Canada

Ari Ercole MB BChir MA PhD FRCA FFICM

Consultant in Neurocritical Care,

Neurosciences Critical Care Unit,

Cambridge University Hospitals NHS

Foundation Trust, Cambridge, UK

Darren H Freed MD PhD FRCSC

Associate Professor of Surgery and

Physiology, Head, Surgical Heart Failure

Program, Cardiac Sciences Program, St

Boniface Hospital, Winnipeg, Manitoba,

Canada

John Fuller MD FRCPC

Professor, Department of Anesthesia and

Perioperative Medicine and Division of

Critical Care (Department of Medicine),

Schulich School of Medicine and Dentistry,

Western University, London Health

Sciences Centre and St Joseph’s Healthcare

London, London, Ontario, Canada

Julio P Zavala Georffino MD

Department of Medicine (Nephrology

section), Geisel School of Medicine,

Dartmouth, NH, USA

RT Noel Gibney MB FRCPC

Professor, Division of Critical Care

Medicine, Faculty of Medicine and

Dentistry, University of Alberta,

Edmonton, Alberta, Canada

Jeff Granton MD FRCPCAssociate Professor, Department ofAnesthesia and Perioperative Medicine andDivision of Critical Care (Department ofMedicine), Schulich School of Medicine andDentistry, Western University, LondonHealth Sciences Centre and St Joseph’sHealthcare London, London, Ontario, CanadaDonald EG Griesdale MD MPH FRCPCAssistant Professor, Department ofAnesthesia, Pharmacology andTherapeutics, Department of Medicine,Division of Critical Care Medicine,University of British Columbia, Vancouver,British Columbia, Canada

Arun K Gupta MBBS MA PhD FFICMFRCA FHEA

Director of Postgraduate Education,Academic Health Sciences Centre, CambridgeUniversity Health Partners, Consultant inAnaesthesia and Neurointensive Care,Cambridge University Hospitals NHSFoundation Trust, Cambridge, UKWael Haddara BSc MD FRCPCAssociate Professor, Department ofMedicine, (Division of Endocrinology andMetabolism and Division of Critical CareMedicine), Schulich School of Medicineand Dentistry, Western University,London, Ontario, Canada

Ahmed F HegazyAssistant Professor, Department ofAnesthesia and Perioperative Medicine,Schulich School of Medicine and Dentistry,Western University, London HealthSciences Centre and St Joseph’s HealthcareLondon, London, Ontario, CanadaUmjeet Singh Jolly BSc MD FRCPCCardiology Fellow, Schulich School ofMedicine and Dentistry, WesternUniversity, Division of Cardiology(Department of Medicine), UniversityHospital, London Health Sciences Centre,London, Ontario, Canada

Philip M Jones MD FRCPC

Associate Professor, Department of

Anesthesia and Perioperative Medicine

and Division of Critical Care (Department

of Medicine), and Department of

Epidemiology & Biostatistics, Schulich

School of Medicine and Dentistry, Western

University, London Health Sciences Centre

and St Joseph’s Healthcare London,

London, Ontario, Canada

Ilya Kagan MD

Senior Physician, General Intensive Care

Department, Rabin Medical Centre,

Beilinson Campus, Petah Tikva, Israel

Kala Kathirgamanathan MD FRCPC

Division of Cardiology, Department of

Medicine, Schulich School of Medicine and

Dentistry, Western University, London,

Ontario, Canada

Harneet Kaur MD

Department of Medicine (Nephrology

Section), Geisel School of Medicine,

Dartmouth, NH, USA

John Kellett MD FRCPI

Consultant Physician, Nenagh Hospital,

Nenagh, County Tipperary, Ireland

Bhupesh Khadka MD

Department of Medicine (Nephrology

section), Geisel School of Medicine,

Dartmouth, NH, USA

Biniam Kidane MD MSc FRCSC

Thoracic Surgery Fellow, Department of

Surgery, University of Toronto, Toronto,

Ontario, Canada

Carlos Kidel MB ChB FRCA

Obstetric Anaesthetic Fellow, Department

of Anaesthesia, Royal Free Hospital,

London, UK

Anand Kumar MD FRCPC

Professor, Departments of Medicine,

Medical Microbiology and Pharmacology/

Therapeutics, University of Manitoba,Winnipeg, Manitoba, Canada

Alejandro Lazo-Langner MD MScAssistant Professor of Medicine, Oncology,and Epidemiology and Biostatistics,Schulich School of Medicine and Dentistry,Western University, London HealthSciences Centre and St Joseph’s HealthcareLondon, London, Ontario, Canada

David Leasa MD FRCPCProfessor of Medicine, Schulich School ofMedicine and Dentistry, Western

University, Consultant, Divisions ofCritical Care Medicine and Respirology,Department of Medicine and Critical Care,London Health Sciences Centre, London,Ontario, Canada

W Robert Leeper MD FRCSCTrauma and Acute Care Surgery JohnsHopkins Hospital, Baltimore, MD, USAStephen Y Liang MD

Instructor, Divisions of Infectious Diseasesand Emergency Medicine, WashingtonUniversity School of Medicine, St Louis,Missouri, USA

Tania Ligori BSc MD FRCPCAssistant Clinical Professor, Department ofAnesthesia and Department of Critical Care,

St Joseph’s Healthcare, Hamilton, McMasterUniversity, Hamilton, Ontario, CanadaJaimie Manlucu MD, FRCPC

Assistant Professor, Schulich School ofMedicine and Dentistry, WesternUniversity, Clinical CardiacElectrophysiologist, Division of Cardiology(Department of Medicine), UniversityHospital, London Health Sciences Centre,London, Ontario, Canada

Janet Martin PharmD, MSC(HTA&M),PhD

Director, Medical Evidence | DecisionIntegrity | Clinical Impact (MEDICI),

List of contributors ix

Co-Director, Evidence-Based Perioperative

Clinical Outcomes Research (EPiCOR),

Assistant Professor, Department of

Anesthesia and Perioperative Medicine and

Department of Epidemiology and

Biostatistics, Schulich School of Medicine

and Dentistry, Western University,

London, Ontario, Canada

Ian McConachie MB ChB FRCA FRCPC

Associate Professor, Department of

Anesthesia and Perioperative Medicine,

Schulich School of Medicine and

Dentistry, Western University, London

Health Sciences Centre and St Joseph’s

Healthcare London, London, Ontario,

Canada

Alan McGlennan MB BS FRCA

Consultant Anaesthetist, Department of

Anaesthesia, Royal Free Hospital,

London, UK

Lauralyn McIntyre MD MSc FRCPC

Assistant Professor, Department of

Medicine (Critical Care), Ottawa Hospital,

Scientist, Ottawa Hospital Research

Institute, Centre for Transfusion and

Critical Care Research, Adjunct

Scientist, Canadian Blood Services, Ottawa,

Canada

Tina Mele MD, PhD FRCSC

Assistant Professor, Department of Surgery

and Division of Critical Care (Department

of Medicine), Schulich School of Medicine

and Dentistry, Western University, London

Health Sciences Centre and St Joseph’s

Healthcare London, London, Ontario,

Canada

MJ Naisbitt FRCA FFICM DICM

Consultant in Critical Care, Salford Royal

Foundation Trust, Salford, UK

Raj Nichani FRCA

Consultant in Anaesthesia and Critical

Care, Blackpool Teaching Hospitals NHS

Foundation Trust, Blackpool, UK

Daniel H Ovakim MD MSc FRCPCCritical Care Medicine, Vancouver HealthIsland Health Authority, Victoria, BritishColumbia, Canada; Medical Toxicology,British Columbia Drug and PoisonInformation Center Vancouver, BritishColumbia, Canada

Neil Parry MD FRCSCGeneral Surgery, Trauma and Critical Care,Director of Trauma, LHSC, AssociateProfessor of Surgery, Western University,London Health Sciences Centre and St.Joseph’s Healthcare London, London,Ontario, Canada

Daniel Castro Pereira MDDepartment of Medicine (Nephrologysection), Geisel School of Medicine,Dartmouth, NH, USA

Thomas Piraino RRTAssistant Clinical Professor (Adjunct),Department of Anesthesia (Critical Care),Faculty of Health Sciences, McMasterUniversity, Best Practice Clinical Educator,Respiratory Therapy Services, St Joseph’sHealthcare, Hamilton, Ontario, CanadaBrian Pollard BPharm MB ChB MD FRCAMEWI

Professor of Anaesthesia, ManchesterMedical School, The University ofManchester, Consultant in Anaesthesia andIntensive Care, Manchester Royal

Infirmary, Manchester, UKValerie Schulz MD FRCPC MPHAssociate Professor, Department ofAnesthesia and Perioperative Medicine,Schulich School of Medicine and Dentistry,Western University, Director of PalliativeCare, London Health Sciences Centre and

St Joseph’s Healthcare London, London,Ontario, Canada

Michael D Sharpe MD FRCPCProfessor, Department of Anesthesia andPerioperative Medicine and Division of

Critical Care (Department of Medicine),

Schulich School of Medicine and Dentistry,

Western University, London Health

Sciences Centre, London, Ontario, Canada

Rohit K Singal MD MSc FRCSC

Assistant Professor of Surgery, Cardiac

Sciences Program, St Boniface Hospital,

Winnipeg, Manitoba, Canada

Pierre Singer MD

Professor, Director General Intensive Care

Department, Rabin Medical Center,

Beilinson Campus, Petah Tikva, Israel

Mark Soth MD FRCPC

Associate Professor, Department of

Medicine, McMaster University, Chief,

Department of Critical Care, St Joseph’s

Healthcare, Hamilton, Ontario, Canada

Christian P Subbe DM FRCP

Senior Clinical Lecturer, School of Medical

Sciences, Bangor University, Consultant

Acute, Respiratory and Critical Care

Medicine, Ysbyty Gwynedd, Bangor, UK

Jaffer Syed MD, MEd, FRCPC

Division of Cardiology, Department of

Medicine, McMaster University, Hamilton,

Ontario, Canada

Ravi Taneja FFARCSI, FRCA, FRCPC

Associate Professor, Department of

Anesthesia and Perioperative Medicine and

Division of Critical Care (Department of

Medicine), Schulich School of Medicine

and Dentistry, Western University, London

Health Sciences Centre and St Joseph’s

Healthcare London, London, Ontario,

Canada

Tom Varughese MD

Department of Anesthesia and

Perioperative Medicine and Division of

Critical Care (Department of Medicine),

Schulich School of Medicine and Dentistry,

Western University, London HealthSciences Centre and St Joseph’s HealthcareLondon, London, Ontario, Canada

Jennifer Vergel Del Dios MDDepartment of Anesthesia andPerioperative Medicine and Division ofCritical Care (Department of Medicine),Schulich School of Medicine and Dentistry,Western University, London HealthSciences Centre and St Joseph’s HealthcareLondon, London, Ontario, Canada

Jessie R Welbourne MB ChB FRCAConsultant in Intensive Care Medicine,Derriford Hospital, Plymouth HospitalsNHS Trust, Plymouth, UK

Christopher W White MDCardiac Sciences Program, St BonifaceHospital, Winnipeg, Manitoba,

CanadaRebecca P Winsett PhD RNNurse Scientist, St Mary’s Medical Center,Evansville, IN, USA

Titus C Yeung MD FRCPCDepartment of Medicine, Division ofCritical Care Medicine, University ofBritish Columbia, Vancouver BritishColumbia, Canada

G Bryan Young MD, FRCPCDepartments of Clinical NeurologicalSciences and Medicine (Critical Care),Schulich School of Medicine and Dentistry,Western University, London, Ontario,Canada

Shelley R Zieroth MD FRCPCAssistant Professor of Medicine, Director,

St Boniface Hospital Heart Failure andTransplant Clinics, Head, Medical HeartFailure Program, Cardiac SciencesProgram, St Boniface Hospital, Winnipeg,Manitoba, Canada

List of contributors xi

Preface to the third edition

 This text is aimed primarily at trainees working in intensive care – especially

multidisciplinary trainees being exposed to the intensive care unit (ICU) for the firsttime It may also be of interest to ICU nurses looking for information on modernmedical (in the strictest sense) approaches to ICU therapy A basic knowledge ofphysiology and pharmacology is assumed, as well as either a medical background oradvanced nursing experience in intensive care

 It may also be a useful “aide memoire” for specialist ICU examinations

 The editors have enlisted a multinational team of contributors active in both practiceand training from institutions on both sides of the Atlantic and beyond The aim hastherefore been to produce a text of international relevance

 The authors are all either experienced ICU practitioners or invited experts on specialistissues Being involved in ICU research was not a pre-requisite although many of theauthors have been or are involved in ICU research

 This text aims to provide practical information on the management of common and/orimportant problems in the critically ill patient, as well as sufficient backgroundinformation to enable understanding of the principles and rationale behind theirtherapy We hope it will prove useful at the bedside, but we would like to emphasize thatthis, or any other book, is no substitute for experienced supervision, support andtraining

 Throughout, the importance of cardiac function is emphasized

 This text does not aim to cover all of ICU practice and is not a substitute to the majorICU reference textbooks For example, practical aspects of monitoring techniques arenot covered (best learnt at the bedside), but the philosophy of monitoring is coveredwhere necessary to illustrate important management points Similarly, pathophysiology

is included to help understand management principles

 The third edition contains several new chapters on topical aspects of ICU therapy, aswell as revisions of older chapters– many have been completely rewritten

 The format is designed to provide easy access to information presented in a concisemanner We have tried to eliminate all superfluous material Selected important orcontroversial references are presented, as well as suggestions for further reading

xiii

Oxygen delivery¼ cardiac output × oxygen content in arterial blood

Oxygen is carried in the blood in two forms:

1 Bound to hemoglobin (the amount of oxygen bound to hemoglobin depends on oxygensaturation)

2 Dissolved in plasma (the amount of oxygen dissolved in plasma depends on the arterialpartial pressure of oxygen (PaO2) and the solubility of oxygen)

Arterial oxygen content¼ oxygen bound to hemoglobin + oxygen dissolved in plasmaMost of the oxygen in blood is carried bound to hemoglobin, and only a small fraction isdissolved Clinically, this means that an arterial oxygen saturation of 90% (corresponding to

a PaO2 of ~60 mmHg) provides essentially normal arterial oxygen content Oxygensaturation is measured noninvasively using pulse oximetry

Arterial oxygen content¼ oxygen bound to hemoglobin + oxygen dissolved in plasmaArterial oxygen content (CaO2)¼ (hemoglobin)(oxygen saturation) (1.34)

+ (PaO2) (0.031)The usual arterial oxygen saturation is close to 100%, and PaO2is approximately 90 mmHg.Arterial blood normally contains approximately 200 mL of oxygen per liter of blood If weassume a cardiac output of ~5 L/min then this is an oxygen delivery of ~1 L/min

Oxygen consumption

Oxygen is carried to the tissues and delivered to cells via the capillaries, where oxygen istaken up (consumed) by cells, so that venous blood contains less oxygen (and more carbondioxide) than arterial blood The partial pressure of oxygen in the venous blood (PvO2) is,

on average, ~40 mmHg (this corresponds to an oxygen saturation of ~70–75% in thevenous blood)

Handbook of ICU Therapy, third edition, ed John Fuller, Jeff Granton and Ian McConachie Published

by Cambridge University Press © Cambridge University Press 2015

1

The overall oxygen content of venous blood is ~150 mL of oxygen/liter of blood Overalloxygen consumption is ~250 mL of oxygen per minute; if delivery is ~1 L/min this means

we usually extract about 25% of the oxygen delivered

 Oxygen consumption (demand) will increase with exercise or fever

 Sedation, paralysis and hypothermia decrease oxygen consumption

Venous oxygen saturation

Venous oxygen saturation (SvO2) reflects oxygen supply and demand; venous oxygensaturation will decrease if there is a decrease in oxygen delivery or an increase in oxygenconsumption, because cells will extract more oxygen from the blood to meet demand [1].Venous oxygen saturation can be monitored either:

 Intermittently, with blood gas sampling from a central venous catheter in the superiorvena cava, or from the pulmonary artery using a pulmonary artery catheter

A decrease in venous oxygen saturation below the usual value of ~70–75% suggestsincreased oxygen extraction and an oxygen supply/demand imbalance Increasing oxygendelivery with inotropic support, or red blood cell transfusion if the hemoglobin is low, mayimprove patient outcomes in sepsis [3]

 A normal SvO2, however, does not necessarily reflect normal oxygen delivery becausevenous oxygenation is a flow-weighted average of venous blood (no flow in means noflow out of tissues)

 In some clinical situations, in particular sepsis, there is maldistribution of flow at themicrovascular level A normal or high venous oxygen saturation may be associated with

a worse prognosis in these patients [4]

Lactic acid is a by-product of anaerobic metabolism Monitoring lactate levels as anindicator of tissue ischemia and anaerobic metabolism may also be used to monitorresponse to therapy [5–7]

Cardiac function

Cardiac output

Cardiac output (CO) is the volume the heart ejects over time (usually expressed as L/min), anormal cardiac output is about 5 L/min Normal cardiac output varies with the size of apatient (you would expect a 200 kg patient to have a higher cardiac output than a 50 kgpatient because of the increased body mass that must be perfused) In order to standardizemeasurements cardiac output is divided by a patient’s body surface area (BSA) to calculatethe cardiac index (CI) The normal CI is 2.5–4 L/min/m2

Cardiac index (CI)¼ CO/BSA

Stroke volume (SV) is the volume of blood ejected with a single contraction (because theright and left ventricle are in series, it follows that the stroke volume of the right ventriclemust be the same as the left ventricle) Cardiac output over a minute therefore is the strokevolume multiplied by the number of beats per minute (or heart rate)

Stroke volume is determined by:

1 Preload– the end-diastolic volume of the ventricle

2 Afterload– the wall tension the ventricle must develop to eject blood

3 Contractility (or inotropy)– the intrinsic performance of the heart at a given preloadand afterload

 An increase in heart rate increases myocardial oxygen demand, which may precipitatecardiac ischemia, and decreases the time available for diastolic filling

Overall, the optimal heart rate is determined by a combination of the treppe phenomenonand the need for diastolic filling time, as well as other factors in individual patients such asintrinsic contractility, and valvular or ischemic heart disease

Stroke volume

The normal ventricle ejects approximately 70 mL of blood with each beat– this is the strokevolume (SV) The ventricles do not empty completely with contraction, there is someresidual volume remaining at the end of systole (end-systolic volume) During diastolethe ventricles fill; a normal end-diastolic volume (EDV) is approximately 120 mL.Ejection fraction

Ejection fraction is defined as the ratio of SV/EDV A normal ejection fraction is 60–65%

Cardiac output

Heart rate Stroke volume

Preload Afterload Contractility

Chapter 1: Oxygen delivery, cardiac function and monitoring 3

Preload is defined as the end-diastolic volume (EDV) of the left ventricle

The determinants of preload include:

 Circulating blood volume – more volume increases preload

 Venous tone – venoconstriction increases preload Venous tone determines venouscapacitance (the veins are the major reservoir for blood volume)

 Ventricular compliance – a more compliant ventricle can hold more blood at a givenpressure than a noncompliant (stiff) ventricle

 Afterload – if afterload is increased acutely, less blood is pumped out with ventricularcontraction, which leaves more residual blood to add on to end-diastolic volume.Preload therefore is increased (this is one of the acute compensatory responses to anincrease in afterload)

 Atrial contraction – especially in patients with stiff noncompliant ventricles, by forcingsome additional blood into the ventricles from the atria during late diastole

 Intrathoracic pressure – increased pressure in the thorax can reduce venous return to theheart; intrathoracic pressure is increased with positive-pressure ventilation and the use ofpositive end-expiratory pressure with mechanical ventilation Hypovolemic patients maybecome hypotensive with intubation and positive-pressure ventilation because of theincreased intrathoracic pressure and decreased venous return to the right ventricle

An increase in preload (end-diastolic volume of the ventricle) and hence muscle-fiber lengthincreases resting tension, velocity of tension development and peak tension:

 This allows for greater stroke volume and therefore cardiac output This is theFrank–Starling relationship

 Excessive ventricular volume, however, will eventually overwhelm the ventricle’s capacity

to pump blood forward, and lead to decompensation As well, a ventricle with poorsystolic function has less capacity to improve contractility with an increase in preload.Clinically we cannot easily measure preload Central venous pressure or pulmonary capil-lary wedge pressure measurements provide information about ventricular filling pressures;however, correlation with intravascular and intraventricular volume depends on manyfactors, such as vascular tone and ventricular compliance

Afterload

Afterload is the wall tension or stress the ventricle must develop to eject blood The law ofLaplace states that tension is proportional to both the pressure and radius of a sphere,divided by twice the wall thickness This equation assumes that the ventricles are spheres.Although the ventricles are not true spheres, pressure, radius and wall thickness contribute

to ventricular afterload

Tension ~ (pressure × radius)/(wall thickness × 2)

 Afterload will therefore be increased if the ventricle generates higher pressures orbecomes larger (dilates) This means that the afterload for the left ventricle is normallyhigher than for the right ventricle– it is larger and develops much higher pressures This

is offset somewhat by the fact that the left ventricle is more muscular, with a thicker wallthan the right ventricle

 Afterload to the ventricle includes a component of preload (ventricular size or radius),therefore afterload and preload are interdependent.

 In a normal heart, changes in afterload do not impact stroke volume until extremevalues are reached; however, a ventricle with decreased contractility (a“failing

ventricle”) is very sensitive to an increase in afterload

Clinically, we often simplify the concept of afterload to refer to the pressure the ventriclegenerates; we can measure blood pressure quite easily, but it is much more difficult toquantify the size of a ventricle or its wall thickness

 Typical conditions that will increase the afterload of the left ventricle are hypertensionand aortic stenosis (aortic stenosis produces a pressure gradient between the leftventricle and aorta)

 Examples of diseases that increase afterload to the right ventricle include pulmonaryhypertension and pulmonary embolism

 A chronic increase in afterload leads to compensatory ventricular hypertrophy An acuteincrease in afterload can cause acute cardiac dilatation

 A clinical example is acute massive pulmonary embolism leading to increased pulmonaryartery pressures and acute right ventricular dilatation seen on echocardiography

Compliance

Compliance is the relationship between volume and pressure

Compliance¼ Δ volume/Δ pressure

The concept of compliance applies to the heart and diastolic function

 Ventricular volume can be increased in the normal ventricle with little change inpressure, but as ventricular end-diastolic volume increases further, the diastolicintraventricular pressure will increase

 With a less compliant (stiffer or less distensible) ventricle, the same end-diastolicvolume is associated with a higher left-ventricular diastolic pressure

Contractility

Inotropy or contractility is the intrinsic ability of cardiac muscle cells to shorten in response

to a stimulus (the stimulus is an action potential); shortening of cardiac muscle tissueresults in ejection of blood An increase in contractility results in a higher stroke volume.Inotropy can be acutely (myocardial infarction) or chronically (systolic heart failure)reduced Clinically this is seen as a reduction in ejection fraction of the left ventricle Theautonomic nervous system is responsible for controlling the inotropic state of the heart

 Increased levels of circulating catecholamines result in greater contractility and anincrease in heart rate (mediated by the adrenergicβ-receptors), as well as increasedvascular resistance (vasoconstriction mediated by the adrenergicα-receptors)

 Inotropic medications (such as dopamine, dobutamine or epinephrine) can be given asintravenous infusions to increase cardiac contractility

 These medications, however, may cause tachycardia, arrhythmias and increasedmyocardial oxygen consumption predisposing to myocardial ischemia [8]

Chapter 1: Oxygen delivery, cardiac function and monitoring 5

The right and left ventricles: similar but different

The right ventricle (RV) pumps blood to the relatively low-pressure, low-resistance ary system Pulmonary hypertension is defined as a mean pulmonary artery pressure of>25mmHg, or a pulmonary vascular resistance of>3 Wood’s units); the left ventricle generateshigher pressures (the normal systemic mean arterial pressure is ~65 mmHg or more)

pulmon- The normal right ventricle is less muscular than the left ventricle (LV) anatomically Theright ventricle may hypertrophy over time (for example in patients with chronicpulmonary hypertension), just as the left ventricle may hypertrophy when faced with anincrease in afterload

 The right ventricle may acutely dilate with a sudden increase in afterload For example,

in a patient with acute pulmonary embolism a sudden increase in pulmonary arterypressure can lead to acute right ventricular dilation and RV failure

 With severe RV dilation the RV may “push” the interventricular septum over toward the

LV, impacting left ventricular diastolic filling, compliance and systolic function Thisphenomenon is known as“ventricular interdependence” [9]

Coronary blood flow to the right ventricle occurs throughout the cardiac cycle– duringboth systole and diastole– because the right ventricle systolic pressures are not high enough

to compress the coronary blood vessels Maximal coronary blood flow to the left ventricle,however, occurs during early diastole With the left ventricle there is actually a brief reversal

of coronary flow during systole, as the muscular left ventricle contracts and generates highsystolic pressures

 Right heart failure is associated with an increase in right-sided pressures – clinically this

is seen as elevated jugular venous pressure or central venous pressure– this pressuremay be transmitted downstream causing congestion of the liver, ascites formation andperipheral edema

 Patients can have biventricular failure (both right and left ventricular failure), pure sided heart failure (for example, with chronic pulmonary hypertension), or left-sided failure

right- Note, however, that with chronic left-heart failure the left-sided pressures will beincreased, and the right ventricle will have to pump against these higher pressures,eventually causing the right ventricle to fail also; in fact the most common cause ofright-sided failure is chronic left-heart failure

Monitoring may allow us to:

 intervene therapeutically in emergency situations,

 guide and plan future therapy,

 establish diagnoses,

 establish prognosis

Monitoring, however, is not a therapy in itself; in order for monitoring to improve outcome

it must be correctly interpreted and acted upon, and done with the minimum ofcomplications

Oxygen saturation monitoring (pulse oximetry)

Oxygen saturation monitors (pulse oximetry) use two different wavelengths of light in thered and infrared spectrum, which are absorbed differentially by oxyhemoglobin anddeoxyhemoglobin The pulse oximeter separates the pulsatile component of the absorptionsignal from the nonpulsatile component– the assumption being that the pulsatile compon-ent represents arterial blood

 If a patient is hypotensive or severely vasoconstricted, the pulse oximeter may not beable to detect an accurate signal

 The pulse oximeter shines the light through tissue (usually a finger, but earlobe, noseetc can be used) and then determines how much of each wavelength was absorbed– andcalculates the oxygen saturation

 Since the absorption spectrum of carboxyhemoglobin (COHb) and oxyhemoglobin withthe light wavelengths used in pulse oximetry are similar, the oximeter will give a falselyhigh oxygen saturation reading with carbon monoxide poisoning Similarly

methemoglobinemia may interfere with accurate pulse oximetry [10]

Noninvasive blood pressure monitoring

NIBP stands for noninvasive blood pressure and uses a blood pressure cuff, with a machinethat automatically inflates and deflates the cuff Noninvasive blood pressure devices providesystolic, diastolic and mean arterial pressure, as well as an audible alarm system, and can beprogrammed to measure BP as often as required clinically (as often as every minute in anunstable patient) The measurement is based on oscillometry; variations in the pressure inthe BP cuff due to arterial pulsations are sensed by the monitor (if you take a blood pressuremanually you will note these oscillations yourself as small deflections in the sphygmoman-ometer as you deflate the cuff) The pressure at which oscillations are maximal correlateswith mean arterial pressure; systolic and diastolic pressures are calculated using a formulabased on the peak of the oscillations

 Automated NIBP measurements correlate closely with directly measured BP (standardsrequire that error be less than 5 ± 8 mmHg with respect to reference standard); inseverely hypotensive patients it may be impossible to measure BP using NIBP

 Noninvasive blood pressure measurements will be less accurate (just as manual BPmeasurement is) if the BP cuff is the incorrect size

 Complications of NIBP measurement that have been described include petechiae,bruising, and neuropathy (if the cuff compresses a nerve)

Direct arterial blood pressure measurement

 The insertion of a small (common sizes are 20 or 22 gauge) teflon-coated catheter into

an artery (usually the radial, ulnar, brachial, dorsalis pedis or femoral are used) allows

Chapter 1: Oxygen delivery, cardiac function and monitoring 7

direct beat-to-beat assessment of the systemic BP [11] This may be required inpatients with hemodynamic instability, or with the use of inotrope or vasopressorinfusions.

 The presence of an arterial line also provides access for the measurement of arterialblood gas samples

 Complications include local bleeding and infection Serious complications includethrombosis and development of arterio-venous (AV) fistulas

 Accurate pressure measurement requires zeroing of the transducer (opening thetransducer to atmospheric pressure and identifying that as a pressure of“zero”)

 In addition, the height of the transducer relative to the patient is important – thetransducer should be positioned at the level of the mid-axillary line, 4th intercostal space

of the patient (at the level of the heart) If the transducer was inadvertently raised to

14 cm above the patient, for example, the pressure reading would be ~ 10 mmHg lowerthan the true reading

 Other reasons for inaccuracy of invasive pressure monitoring include damping orunder-damping of the pressure trace The pressure waveform may be“damped” if thecatheter is kinked, or with blood or air within the catheter It is also possible for thepressure waveform to be“under-damped” – typically recognized as a rapid, spikedupstroke in the waveform with a systolic pressure overshoot This occurs when thepressure waveform in the catheter causes the transducer to reverberate at its ownharmonic frequency Typically, mean pressures are more accurate in the presence ofunder-damped system

Central venous pressure (CVP) monitoring

Central venous catheters may be used to:

 Monitor central venous pressure

 Provide central venous access for infusions of potent vasoconstrictors or hypersosmolarsolutions such as total parenteral nutrition or both

 Central venous pressure (pressure in the superior vena cava) may be monitored withjugular, subclavian or peripherally inserted central venous catheters [12]

 Femoral venous catheters are not useful for monitoring of central venous pressure

 Accurate measurement of CVP requires that the catheter be zeroed, and the

transducer leveled at the mid-axillary fourth intercostal space (as for arterial

catheters) [13]

In addition CVP will fluctuate with changes in intrathoracic pressure:

 In a spontaneously breathing patient the CVP will decrease on inspiration as

intrathoracic pressure decreases; with positive-pressure ventilation the CVP willincrease on inspiration due to increased intrathoracic pressure

 The actual filling pressure (transmural pressure) for the right ventricle is the CVPmeasured when intrathoracic pressure is zero– this will tend to be at end-expiration

 For patients on positive end-expiratory pressure (PEEP), particularly levels over 10 cm

H2O, the CVP will be increased relative to the true filling pressure; the actual amount ofincrease can only be measured using a measurement of intrathoracic pressure (such as apleural or esophageal pressure manometer)

CVP is often used as a guide for fluid management:

 A protocol for therapy in patients with early sepsis (within 6 hours), which included agoal of CVP of 8–12 mmHg, and additional fluid resuscitation to meet the target CVP,was associated with improved outcome [3]

 Ongoing aggressive fluid resuscitation after the initial early resuscitation, however, maynot be beneficial [14,15]

CVP is not an accurate surrogate for intravascular volume The CVP depends on manyfactors:

 Patients may have a low CVP with a normal intravascular volume (for example withvasodilation, or a compliant right ventricle)

 Patients may have a higher than normal CVP and have a low intravascular volume, orbenefit from additional fluid challenge (for example, with vasoconstriction, highintrathoracic pressure due to positive end-expiratory pressure, cardiac tamponade, orpulmonary hypertension and right-heart failure)

Clinically, patient assessment for intravascular volume status should include heart rate,blood pressure, capillary refill, urine output, response to previous fluid challenges, inotropeand vasopressor requirements, and overall fluid balance, venous oxygen saturation, lactatelevels etc., as well as any trends in monitored parameters

Other ways to assess cardiac function and intravascular volume Pulse pressure variation (PPV)

 Pulse pressure variation is the cyclic variation in pulse pressure and systolic bloodpressure with respiration due to changes in intrathoracic pressure; pulse pressure will bemaximal at the end of inspiration and minimal during exhalation (in a mechanicallyventilated patient); the PPV response is exaggerated in patients with“preload reserve”[16,17]

 Pulse pressure variation can be used to predict response to fluid challenge (volumeresponsiveness)

Limitations of PPV monitoring include:

 Requires patients to be on positive-pressure ventilation; spontaneous breathing attempts(including triggering) will lead to changes in venous return and make PPV analysisinaccurate

 Patients must be in sinus rhythm

 PPV may be less accurate in patients with elevated filling pressures [17]

 Tidal volume is important – a small tidal volume (resulting in smaller changes inintrathoracic pressure) will make PPV inaccurate; a tidal volume of at least 8 mL/kgPBW is required [17]

 Visualization of the inferior vena cava (IVC) as it enters the right atrium providesinformation about the size of the IVC, and in spontaneously breathing patients

“collapse” of the IVC (or a decrease in diameter of over 30%) on inspiration suggestspreload responsiveness

 Cyclic variation in IVC volume/diameter may predict fluid responsiveness in amechanically ventilated patient; however, large tidal volumes (at least 8 mL/kg PBW arerequired, even temporarily) and spontaneous breathing attempts are required for thisassessment [18]

Pulmonary artery catheters

Pulmonary artery catheters (PAC) are catheters that use a distal balloon filled with 1.5 mL

of air to“float” the catheter:

 from the central vein into the right atrium (pressure measured from the tip of thecatheter will show a typical venous waveform), then

 across the tricuspid valve and into

 the right ventricle (as the catheter enters the right ventricle the waveform will show anincrease in systolic pressure with the diastolic pressure approximately equal to thevenous and atrial pressure) Typical RV pressure, in the absence of pulmonaryhypertension is ~ 20–25 mmHg/0–8 mmHg The catheter will then float across thepulmonic valve and into

 the pulmonary artery As the catheter crosses the pulmonic valve the waveform of thesystolic pressure will be unchanged, but the diastolic pressure will increase– typically to

10–15 mmHg If the balloon is left inflated the catheter will continue to float along thepulmonary artery until it“wedges” and cannot float any further distally At this pointthe pressure monitored from the tip of the catheter will be

 the pulmonary wedge pressure – this pressure reflects left atrial pressure (since there

is an uninterrupted column of blood from the tip of the catheter to the left atrium, and azero flow state since the catheter is occluding flow) This pressure is sometimes alsocalled pulmonary artery occlusion pressure

Pulmonary artery catheters have the ability to measure CVP (from the CVP port which is

~ 30 cm proximal to the catheter tip) as well as pulmonary artery pressure and thepulmonary wedge pressure

Pulmonary artery catheters can also measure cardiac output using a principle known asthermodilution There is a thermistor (temperature monitor) at the tip of the PAC If

a known quantity of fluid (typically 10 mL) at a known temperature (typically roomtemperature or ice-cold saline is used) is injected proximal to the thermistor (through theCVP port) the distal thermistor will detect a decrease in temperature relative to the baselinepulmonary artery temperature In patients with a high cardiac output the relatively coldbolus of saline will be“diluted” by the large volume of blood flowing by and the tempera-ture change will be small and short-lived In a patient with a low cardiac output thetemperature decrease will be larger and last longer A computer is used to integrate thearea under the temperature change curve and calculate the cardiac output

Note that cardiac output measurements will not be accurate in patients with tricuspidregurgitation; other causes of cardiac output measurement error include: malpositioning ofthe catheter, rapid infusion of cold solutions (for example blood products) at the time of

thermodilution, cardiac output measurement, injection of an inaccurate volume or perature of the injectate, uneven or slow injection rate.

tem-Although the ability to monitor cardiac output and left-sided filling pressures isintuitively appealing, this does not necessarily translate to benefit for the patient

 A number of studies have shown that use of a pulmonary artery catheter monitor is notassociated with improved outcome in high-risk surgery patients, heart-failure patients,septic patients or patients with acute respiratory distress syndrome [19–21]

 The utilization of PACs has decreased over the past two decades as a result [22].References

1 Walley K Use of central venous oxygen

saturation to guide therapy Am J Resp Crit

Care Med 2011; 184 : 514–20

2 Davison DL, Chawla LS, Selassie L et al

Femoral-based central venous oxygen

saturation not a reliable substitute Chest

2010; 138 : 76–83

3 Rivers E, Nguyen B, Havstad S et al Early

goal-directed therapy in the treatment of

severe sepsis and septic shock NEJM 2001;

345 : 1368–77

4 Pope JV, Gaieski DF, Trzeciak S, Shapiro

NI Multicenter study of central venous

oxygen saturation (ScvO2) as a predictor of

mortality in patients with sepsis Ann

Emerg Med 2010; 55 : 40–6

5 Jones AE, Shapiro NI, Trzeciak S et al

Lactate clearance vs central venous oxygen

saturation as goals JAMA 2010; 303 :

739–46

6 Jackson AE Point: Should lactate clearance

be substituted for central venous oxygen

saturation as goals of early severe sepsis

and septic shock therapy? Yes Chest 2011;

140 : 1406–08

7 Rivers EP, Elkin R, Cannon CM

Counterpoint: Should lactate clearance be

substituted for central venous oxygen

saturation as goals of early severe sepsis

and septic shock? No Chest 2011; 140 :

1408–13

8 DeBacker D, Biston P, Devriendt J et al

Comparison of dopamine and

norepinephrine in the treatment of

shock N Engl J Med 2010; 362 :

779–89

9 Castillo C, Tapson VF Right ventricular

responses to massive and submassive

pulmonary embolism Cardiol Clin 2012;

30 : 233–41

10 Ortega R, Hansen CJ, Ellerman K, Woo A.Videos in clinical medicine Pulse

Oximetry N Engl J Med 2011; 364 : e33

11 Tegtmeyer K, Brady G, Lai S, Hodo R,Braner D Placement of an arterial line

N Engl J Med 2006; 354 : e13

12 Braner D, Lai S, Eman S, Tegtmeyer K.Videos in Clinidal Medicine CentralVenous Catheterization– Subclavian Vein

N Engl J Med 2007; 357 : e26

13 Gelman, S Venous function and centralvenous pressure: a physiologic story.Anesthesiology 2008; 108 : 735–48

14 Vincent JL, Weil MH Fluid challengerevisited Crit Care Med 2006; 34 : 1333–7

15 Durairaj L, Schmidt GA Fluid therapy inresuscitated sepsis: less is more Chest 2008;

133 : 252–63

16 Marik PE, Monnet X, Teboul J

Hemodynamic parameters to guide fluidtherapy Annals Int Care 2011; 1 : 1–9

17 Cannesson M, Aboy M, Hofer C, Rehman

M Pulse pressure variation: where are

we today? J of Clin Monit Comp 2011; 1 :45–56

18 Schmidt GA, Koenig S, Mayo PH Shock:ultrasound guide to diagnosis and therapy.Chest 2012; 142 : 1042–8

19 ESCAPE Investigators Evaluation study ofcongestive heart failure and pulmonaryartery catheterization effectiveness: theESCAPE trial JAMA 2005; 294 : 1625–33

20 Sandham JD, Hull RD, Brant RF et al

A randomized, controlled trial of the use ofpulmonary artery catheters in high-risksurgical patients N Engl J Med 2003; 348 :5–14

Chapter 1: Oxygen delivery, cardiac function and monitoring 11

21 National Heart, Lung and Blood

Institute Acute Respiratory Distress

Syndrome Clinical Trials Network

Pulmonary-artery versus central venous

catheter to guide treatment of acute

lung injury N Engl J Med 2006; 354 :2213–24

22 Weinder RS, Welch G Trends in the use ofthe pulmonary artery catheter in the UnitedStates, 1993–2004 JAMA 2007; 298 : 423–429

 Shock can be defined as a clinical state in which tissue blood flow is inadequate for tissuerequirements (insufficient oxygen delivery), there is maldistribution of oxygen delivery,

or when cellular oxygen utilization is impaired

 At the cellular level, shock is a state of acute nutritional insufficiency for oxygen andother essential substrates, resulting in cellular anoxia, cellular dysfunction, and,eventually, cell death

Pathophysiology

 Although it is common, and in many ways appropriate, to think of shock in

hemodynamic terms (see below), shock is simultaneously a systemic and a cellulardisease leading ultimately to decreased adenosine triphosphate (ATP) production,cell-membrane dysfunction, cellular swelling and cell death

 Once cellular swelling occurs, restoration of local tissue perfusion may not be possible,leading to progressive secondary ischemia

 Damage to other organs such as the lungs results from leukocyte sequestration anddeposition in the pulmonary capillaries– leading to increased pulmonary dead spaceand increased capillary permeability from the release of inflammatory mediators

 The reticulo-endothelial system function is depressed, which decreases clearance of toxicmaterials (e.g endotoxin, foreign proteins, immune complexes and platelet aggregates)

 It is therefore clear how an initial insult to one organ system may quickly result inmultisystem organ failure

Types of shock

There are four types of shock:

Handbook of ICU Therapy, third edition, ed John Fuller, Jeff Granton and Ian McConachie Published

by Cambridge University Press © Cambridge University Press 2015

Type of shock Clinical Examples Comments

With volume depletion, left ventricularpre-load is too low to support adequatestroke volume Compensatory mechanisms

13

The shock cycle

Various shock states may inter-relate clinically to produce a mixed picture

 For example, hypovolemic shock may lead to acidosis and result in secondary

cardiogenic shock, whilst septic shock commonly leads to hypovolemia as a result ofmicrobial toxins and cytokines, which result in increased capillary permeability andleaking of fluid into the interstitial space

 Clinicians must be cognizant of these secondary manifestations of the primaryclinical problem

 When left under-treated, many types of shock will result in hypothermia, coagulopathy,acid–base disturbances, electrolyte abnormalities, cellular injury, multisystem organfailure and, ultimately, death

(cont.)

Type of shock Clinical Examples Comments

begin, including tachycardia, increasedvenous tone, increased vascular resistance,increased myocardial contractility, decreasedurine output and sodium reabsorption.However, compensation can only go so far,and hypovolemic shock develops whenblood loss exceeds 20–25% of normalcirculating volume Prolonged hypovolemicshock leads to metabolic acidosis andsecondary cardiogenic shock

It is important to remember that septic shocksometimes involves myocardial depression,and, in this case, patients may not present withdistributive shock (rather they may havecardiogenic shock)

This type of shock involves impaired diastolicfilling of the heart (such as with cardiactamponade) and/or increased right or leftventricular afterload (such as with severepulmonary embolism or tensionpneumothorax)

Cardiogenic shock results in reduced cardiacoutput due to a problem with one or more of:the myocardium, the heart valves or heartrhythm

Clinical presentation

Shock commonly presents with:

Although not all patients with shock present with arterial hypotension (one can haveshock without hypotension and one can have hypotension without shock), hypotension iscommon enough that analyzing the individual determinants of blood pressure provides auseful schema to think about shock Since blood pressure is equal to the cardiac outputmultiplied by the total peripheral resistance, all types of shock will involve a problem withone or more of pre-load, myocardial contractility, afterload, heart rate (or rhythm) or totalperipheral resistance For example,Figure 2.1shows the reason why a patient with a largeacute myocardial infarction (loss of myocardial contractile function) will have hypotensionand shock

Monitoring

General

All patients should be monitored with continuous ECG and pulse oximetry An arterialcannula is mandatory in most cases of moderate or severe shock, to have blood pressuremeasured beat-to-beat, as well as to facilitate serial measurements of blood gases and lactateconcentration

 It is reasonable to target a mean arterial pressure of over 60–65 mmHg in mostcases of shock

Serial lactate concentrations

Following serial lactate concentrations allows the clinician to assess the efficacy ofinterventions taken to treat shock

 When therapy is effective, the lactate concentration should fall over a matter

of hours

It must be kept in mind, however, that liver dysfunction occurring concurrently with shockwill potentially slow the clearance of lactate from the blood, as the reaction occurring in theliver (converting lactate to pyruvate– the Cori cycle) will occur more slowly

Hypotension Systolic blood pressure <90 mmHg

or mean arterial pressure <60 mmHgTissue hypoperfusion Oliguria <0.5 mL/kg/h

Pale, cool and clammy skin (due to vasoconstriction)Rapid, thready pulse

Altered level of consciousnessInadequate oxygen delivery

to tissue Lactic acidosis (due to anaerobic glycolysis under conditions oflow oxygen tension)

Chapter 2: Shock 15

Central venous cannulation

The severity of shock (except for distributive shock) can be initially assessed and followedusing the mixed venous oxygen saturation (SvO2) of blood taken from the distal port of apulmonary artery catheter

 The normal oxygen saturation of this blood is about 75%, but the saturation will belower in most shock states

The SvO2is completely determined by only four variables (Figure 2.2)

Out of the four variables, two are easily measurable and correctable (arterial saturationusing a pulse oximeter and hemoglobin concentration with a full blood count), leaving onlytwo pertinent variables to consider in most patients: oxygen consumption and cardiacoutput Therefore, in a patient with low SvO2, whose arterial oxygen saturation is normaland whose hemoglobin concentration is normal, the only way for a decreased SvO2to occur

is via either an increase in oxygen consumption or a decrease in cardiac output The latter is

by far the most common reason for decreased SvO2 in hypovolemic, obstructive andcardiogenic shock

 This provides the rationale for using fluids and vasoactive agents in shock (as

appropriate for the diagnosis), and it provides a mechanism to monitor the effectiveness

of interventions taken

The central venous oxygen saturation (ScvO2 – taken from a central line in the superiorvena cava) in healthy volunteers is usually slightly less than the SvO2, but in critically illpatients with shock, it may be higher than the SvO2

 The ScvO2has been shown to be useful in early goal-directed therapy of septicshock [2] and may be a reasonable substitute for a true SvO2in other types of shock [3].This is important, as the pulmonary artery catheter is used infrequently in modernICU practice

VO2

S uO2 = SaO2

-CO ¥ Hb ¥ 1.34

Figure 2.2 Equation for mixed venous oxygen saturation SvO 2 denotes mixed venous oxygen

saturation, SaO 2 is arterial oxygen saturation, VO 2 is oxygen consumption, CO is cardiac output, and Hb is hemoglobin concentration.

Blood pressure

Heart rate

Afterload Contractility

Preload

Stroke volume

Cardiac output Total peripheral resistance

Figure 2.1 Determinants of blood pressure The boxes shaded gray are implicated in shock in a patient with a large myocardial infarction.

Management of shock

Unfortunately, our knowledge of the pathophysiological cellular events in shock outweighour ability to modify these events Therapy is still largely“macroscopic” (i.e restoration oftissue perfusion), not “microscopic.” As well as general management, it is important toprovide specific therapy according to cause

Timing

It is very important to aggressively treat shock states, as the pathological changes seen at amicrocirculatory level can become irreversible after a certain point The earlier treatmentbegins, the less likely multisystem organ failure will occur Resuscitation should start whileconcurrent investigation of the underlying cause of shock is undertaken

Airway, oxygenation and ventilation

The threshold for tracheal intubation and mechanical ventilation of patients with shockshould be low since:

 Patients are likely to have a decreased level of consciousness and therefore are unlikely

to be able to protect their airway Aspiration is a risk

 Mechanical ventilation reduces the work of breathing and oxygen consumption, and ithelps to compensate for a metabolic acidosis

 In cardiogenic shock due to myocardial dysfunction, the addition of positive expiratory pressure can help with cardiac performance by reducing LV afterload.Circulatory support

end-It is necessary to tailor circulatory support to each patient, usingFigure 2.1as a guide andtreating the underlying cause

 A fluid challenge is appropriate in virtually all patients, unless obviously suffering fromgross congestive cardiac failure

 Fluids must be given, but should be given carefully to avoid adverse effects

 At the start of a resuscitation of a patient in shock, fluids should be given rapidly and theresponse of the patient to a fluid challenge (300–500 mL over 20–30 minutes) should beassessed

 If no desirable response is obtained (increase in blood pressure, improved urine output

or decrease in heart rate), aggressive fluid therapy should be stopped in favor ofproviding maintenance fluid requirements only, to prevent fluid overload

 If the central venous pressure rises more than a few millimetres of mercury abovebaseline, this is a warning sign of potential fluid overload [1]

Increasingly, bedside transthoracic or transesophageal echocardiography is used to guidethe diagnosis and therapy of shock

 For instance, in a patient with suspected hypovolemic shock, seeing a low left ventricularend-diastolic diameter (LVEDD), a collapsed inferior vena cava, no evidence ofpericardial effusion and normal LV systolic function confirms the diagnosis, rules outother potential diagnoses (such as cardiac tamponade) and provides direct evidence ofresponse to therapy (increasing LVEDD with fluid transfusion)

Chapter 2: Shock 17

 Stroke volume can be followed with serial measurements of the aortic

velocity–time integral

 For cardiogenic shock due to cardiomyopathy, evidence of poor LV systolic

function will be present, and inotropic/vasopressor support can be dynamicallytitrated to the echocardiographic results in addition to standard resuscitative

endpoints, such as improving mental status, raised blood pressure and increasingurine output

Vasoactive support :

 For many shock states, the vasoactive agent of choice is noradrenaline

(norepinephrine), since it has bothα- and β1-agonist activity and can theoreticallylimit the reduction in cardiac output caused by pureα-agonists such as

 Dobutamine is useful in cardiogenic shock due to cardiomyopathy

Vasoactive agents are discussed more fully in their own chapter

Intra-aortic balloon pump support used to be recommended for many types ofcardiogenic shock, such as acute myocardial infarction However, evidence from a largerandomized clinical trial published in 2012 suggests that there is no mortality benefit to thisintervention [4]

Anaphylactic shock

In anaphylactic shock the trigger stimulus causes release of histamine, serotonin, tryptase,leukotrienes, prostaglandins, kinins and other vasoactive materials, mainly from mast cells.These substances act primarily on smooth muscle, leading to peripheral and airway edema(stridor may not appear until 80% of the airway is obstructed), bronchospasm, vasodilata-tion and capillary leakage Some of the mediators may also act directly on the myocardium.Management includes:

 Withdrawing the trigger stimulus, and then basic life support and cardiopulmonaryresuscitation (CPR)

 Antihistamines are given as a second-line treatment after initial resuscitation.

The evidence supporting antihistamines in anaphylaxis is weak, but logical reasonsexist to give them Agents of choice include chlorphenamine or diphenhydramine.Using H2-antagonists such as ranitidine is no longer recommended

 Steroids such as hydrocortisone are usually administered after the initial resuscitation,but take several hours to have an effect

 Inhaled salbutamol may help to treat bronchospasm

References

1 Vincent JL, De Backer D Circulatory

shock N Engl J Med 2013; 369 : 1726–34

2 Rivers E, Nguyen B, Havstad S et al Early

goal-directed therapy in the treatment of

severe sepsis and septic shock N Engl J Med

J Med 2012; 367 : 1287–96

Chapter 2: Shock 19

3 Oxygen therapy Ahmed F Hegazy and Ian McConachie

“Oxygen lack not only stops the machine but wrecks the machinery”

JS Haldane (1860–1936)

Oxygen is the molecule of life A vast array of intensive care interventions aim to improveoxygen delivery to end-organs In this chapter, we focus on oxygen delivery to the lungs, thevarious oxygen delivery devices (in non-intubated patients), and some of the side effects ofoxygen therapy Long-term oxygen therapy is beyond the scope of this chapter

In simple terms, the amount of oxygen transferred from the lungs into the blood streamcan be increased in one of two ways:

 Increasing the inspired oxygen concentration (FiO2)

 Increasing the mean airway pressure

Increases in mean airway pressure can be achieved by:

 Increasing tidal volume (but high tidal volumes can be detrimental, as discussed in otherchapters in this text)

 Lengthening the I:E ratio

 Adding or increasing positive end-expiratory pressure (PEEP)

Increasing PEEP is arguably the best way to increase mean airway pressure, especially inview of the other beneficial effects of PEEP

Inspired oxygen concentrations can also be easily manipulated by changing the FiO2

on the ventilator or by using different oxygen delivery devices Knowledge of certainphysiologic principles, oxygen delivery devices and pathological conditions that may impairoxygen delivery is paramount

Physiology and pathology

At the cellular level, oxygen is required by mitochondria for the aerobic formation of ATP.Before reaching the mitochondria, however, oxygen needs to cross multiple barriers andexist in different phases Dry atmospheric air at sea level has an oxygen partial pressure(PO2) of 159 mmHg After passing through the alveoli, arterial blood, capillary circulationand the interstitium, it eventually reaches the mitochondria with a PO2of 4 to 22 mmHg.This series of partial pressure reductions is called the oxygen cascade Administering higherinspired oxygen concentrations aims at preventing tissue hypoxia, although this may beonly one of a myriad of interventions necessary to achieve this goal

Handbook of ICU Therapy, third edition, ed John Fuller, Jeff Granton and Ian McConachie Published

by Cambridge University Press © Cambridge University Press 2015

20

Hypoxia can be detrimental at both the tissue and organ system levels The brain seems to

be the most vulnerable organ to the effects of acute hypoxia Acute reductions in arterialoxyhemogblobin saturation, to values below 80%, can cause confusion and agitation, even inhealthy subjects At the tissue level, lack of oxygen delivery can lead to the anaerobic formation

of ATP, a process that involves the generation of lactic acid and may lead to metabolic acidosis.Causes of tissue hypoxia can be classified into four main categories:

1 Hypoxemic hypoxia results from low levels of dissolved oxygen in the blood

Low inspired oxygen concentrations (e.g at high altitudes), respiratory failure andV/Q shunts can all cause hypoxemic hypoxia

2 Anemic hypoxia is usually caused by low hemoglobin levels limiting the amount ofchemically bound oxygen that can be delivered to the tissues Carbon monoxidepoisoning can also reduce the amounts of hemoglobin able to carry oxygen to the tissuesleading to a form of anemic hypoxia

3 Stagnant hypoxia occurs when the oxygen content of blood is normal, but lack

of adequate blood flow results in decreased oxygen delivery This can be regional(e.g secondary to peripheral vascular disease) or global (in cases of low cardiac output)

4 Histotoxic hypoxia occurs when oxygen delivery is normal, but the cellular organellesand mitochondria are unable to utilize oxygen normally Cyanide poisoning is theclassical example of this form of hypoxia

popula-During normal tidal breathing, peak inspiratory flow rates can be as high as 60 L/min

At times of respiratory distress, however, flow rates exceeding 100 L/min are commonlyencountered The amount of oxygen delivered to the trachea with various oxygen deliverydevices depends on the patient’s peak inspiratory flow rate and the flow capacity ofthe device If device flow rates are lower than the patient’s peak inspiratory flow, air will

be entrained into the trachea, diluting the delivered oxygen Using high-flow masks, adding

a reservoir bag and delivering oxygen with a mask seal (e.g CPAP masks) are all ways withwhich delivered oxygen concentrations can be increased

Nasal cannulae

Oxygen concentrations delivered by nasal cannulae depend on the set oxygen flow rate andthe patient’s own inspiratory flows As a general approximation, each increase in the oxygenflow rate by 1 L/min, will increase the FiO2 by around 4% above room air An oxygenflow rate of 6 L/min will deliver the maximal FiO2achievable by nasal prongs, usually inthe range of 40 to 50% Nasal prongs are very well tolerated by patients and are thereforemore likely to be kept on Flow rates in excess of 4–5 L/min can, however, cause nasaldryness, irritation and discomfort, and should generally be avoided

Simple face masks

Side holes in simple face masks allow entrainment of air with high inspiratory flow ratesleading to variable delivered FiO Increasing oxygen flows from 5 to 10 L/min will raise the

Chapter 3: Oxygen therapy 21

delivered oxygen concentrations from approximately 40 to 60% It is not recommended

to reduce oxygen flows below 5 L/min while using simple face masks, as low flows willnot effectively flush CO2from the mask and rebreathing might result

Venturi masks

Specific air entrainment (Venturi) adapters can deliver oxygen concentrations rangingfrom 24 to 50% with fair accuracy These adapters are designed to entrain air with a specificratio to maintain a constant FiO2 Increasing oxygen flows will entrain more air andincrease the total delivered gas flow without altering oxygen concentrations Increasedminute ventilation or hyperventilation will decrease the oxygen concentration delivered

to the trachea [2] Venturi masks are useful when precisely controlled, low-concentrationoxygen supplementation is required, e.g in COPD patients

Non-rebreathing masks

Non-rebreathing masks are equipped with a reservoir bag that is continuously being filledwith the oxygen supply When patients inhale they draw on the high oxygen content ofthe reservoir bag A one-way valve situated at the bag’s entrance prevents exhaled CO2fromentering Oxygen flows of 10 to 15 L/min are required to maintain bag inflation.Non-rebreathing masks are capable of delivering oxygen concentrations in the range of

60 to 90%

Tracheostomy masks

As their name implies, these allow supplemental oxygen delivery to spontaneously breathingpatients with a tracheostomy The delivered oxygen bypasses the upper airway and sohumidification is preferable with any prolonged use Oxygen flows are usually adjusted

to achieve target oxyhemoglobin saturation ranges

Continuous positive airway pressure (CPAP) masks

Continuous positive airway pressure masks improve oxygenation through two mechanisms:

by increasing the mean airway pressures and by reliably delivering high FiO2s A fitting full-face mask or nasal mask can be used and a fixed level of continuous positiveairway pressure and FiO2are prescribed In the expiratory phase, airway pressures are notallowed to return to baseline, in a manner very similar to PEEP, with invasive mechanicalventilation and EPAP (expiratory positive airway pressure) with noninvasive ventilation

tight- This increases the functional residual capacity and helps recruit more alveoli for gasexchange

 Other beneficial effects of CPAP include reducing the work of breathing, relief ofdynamic upper airway obstruction, decreasing preload and afterload, and decreasing thepulmonary vascular resistance [3]

Continuous positive airway pressure is indicated in the treatment of hypoxemia secondary

to obstructive sleep apnea and acute heart failure If patients present with significanthypercapnia, however, noninvasive ventilation might be a better option Other situationswhere CPAP may be beneficial include respiratory failure secondary to splinting followingmajor abdominal surgery and in cases of chest-wall trauma It should be noted, however,

that some people will not tolerate the tight-fitting mask and that prolonged applicationmight lead to local pressure effects on the nasal bridge.

Oxygen therapy in specific illnesses

Supplemental oxygen should be administered with caution to certain patient populations.Chronic obstructive pulmonary disease (COPD)

Patients at risk for hypercapnic respiratory failure, e.g those with COPD (but also patientswith chronic neuromuscular disease or obesity hypoventilation syndrome) may exhibit

a further rise in their arterial CO2levels with excessive oxygen therapy [1]

 In the past, this was thought to be largely the result of an improvement in arterialoxygenation causing a reduction in the hypoxic ventilatory drive

 More recently however, it has been demonstrated that worsening ventilation perfusion(V/Q) mismatching is likely the main reason for this phenomenon The observed V/Qmismatch might be secondary to an exaggerated release of hypoxic pulmonaryvasoconstriction when high-flow supplemental oxygen is administered This in turnmight cause a maldistribution of pulmonary blood flow, leading to an overall increase inalveolar dead space and a rise in arterial CO2

 Oxygen-induced reduction of hypoxic drive and the Haldane effect (increased ability ofdeoxygenated hemoglobin to carry CO2) in COPD may also play a role in increasingarterial CO2in these patients, though their contribution is likely not as significant aspreviously thought [4]

 Patients presenting with acute exacerbations of COPD will have significantly increasedwork of breathing It is important to recognize that an increase in arterial pCO2mayrepresent fatigue and impending respiratory arrest

In patients presenting with acute COPD exacerbations, current guidelines suggest initiatingoxygen therapy with a 24% Venturi mask at an O2 flow of 4 L/min if they are not inextremis [1] Aiming for a target arterial oxyhemoglobin saturation in the range of 88–92%

is recommended with frequent clinical, blood gas and oxyhemoglobin saturation monitorassessment In a prehospital, paramedic randomized study of COPD patients, controlledoxygen therapy was associated with significantly improved survival overall, compared tononcontrolled, high-flow oxygen therapy [5]

Patients with COPD presenting critically ill or in peri-arrest conditions, however,should receive much higher levels of supplemental O2aiming for higher saturations duringtheir initial resuscitation phase In these situations, invasive or noninvasive ventilationmaybe indicated Once more stable, oxygen titration to lower oxyhemoglobin saturationtargets (88–92%) should be resumed It is important to note that profound hypoxemia

is a more imminent threat to life than hypercapnia, and that the effects of prolonged severehypoxia can be much more devastating in the critically ill

Acute coronary syndromes

Classically, oxygen therapy has been a first-line treatment for patients presenting with anacute coronary syndrome Although this makes sense in the setting of myocardial ischemia,

it has been recently suggested that there may be no benefit and a potential for harm with

Chapter 3: Oxygen therapy 23

this practice Routine oxygen administration has been associated with increased infarct size,likely secondary to coronary vasoconstriction [6] This is still controversial and further,ongoing studies are eagerly awaited [7] At present, patients presenting with an acutecoronary syndrome should not be given supplemental oxygen unless hypoxic.

Acute stroke

A similar controversy exists regarding oxygen therapy in acute stroke with, again, studiessuggesting a potential worse outcome when oxygen therapy is routinely administered [8].Shock

Oxygen administration has long been advocated during the treatment of shocked patients.There is some evidence from animal studies that 100% oxygen during treatment ofhemorrhagic shock maintains blood pressure and prolongs survival compared to controls[9] It is thought that oxygen inhalation may reduce the work of breathing in shockedpatients – certainly increased work of breathing may cause diaphragmatic fatigue andanimal studies suggest that respiratory arrest may be the mode of dying in shockedpatients [10]

Hazards of oxygen therapy

Oxygen therapy is not without risk In general, the potential hazards of oxygen therapyinclude its biologic toxic effects and its potential for physical hazards, e.g fires Excessiveoxygen administration has been associated with adverse effects involving several organsystems

Central nervous system (CNS)

Exposure to hyperbaric oxygen at more than 2 atmospheres of pressure may cause ized tonic-clonic (grand mal) seizures This is the Paul Bert effect– first described in thenineteenth century Higher oxygen pressures can induce seizures with shorter durations ofexposure This side effect constitutes the main limitation to increasing oxygen pressures inhyperbaric chambers [12] The mechanism by which hyperbaric oxygen induces seizures isunclear Other CNS manifestations of oxygen toxicity include dizziness, nausea, headaches,disorientation, tinnitus, paresthesias and facial twitching

general-Ocular

Neonatal exposure to high oxygen concentrations can lead to retinopathy of prematurity(ROP) The risk seems to be greatest in the premature and continues up to 44 weeks ofpost-conceptual age Oxygen therapy in neonates at risk should therefore be very tightlycontrolled and their saturations should never be allowed to exceed 95% The mechanism for