Ebook Critical care nephrology (3/E): Part 1

(BQ) Part 1 book Critical care nephrology has contents: The critically ill patient, the pathophysiologic foundations of critical care, mechanical ventilation, monitoring organ dysfunction in critical care, kidney specific severity scores,... and other contents.

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CRITICAL

CARE

NEPHROLOGY

Claudio Ronco, MD

Director, Department of Nephrology, Dialysis

and Transplantation and International

Renal Research Institute (IRRIV)

San Bortolo Hospital

Vicenza, Italy

Rinaldo Bellomo, MB BS (Hons), MD,

FRACP, FCICM, FAAHMS

Department of Intensive Care

Austin Hospital and Royal Melbourne Hospital

Australian and New Zealand Intensive Care

Research Centre

School of Public Health and Preventive

Medicine

Monash University and School of Medicine

The University of Melbourne

Melbourne, Victoria, Australia

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1600 John F Kennedy Blvd.

Ste 1800

Philadelphia, PA 19103-2899

No part of this publication may be reproduced or transmitted in any form or by any means,

electronic or mechanical, including photocopying, recording, or any information storage and

retrieval system, without permission in writing from the publisher Details on how to seek

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can be found at our website: www.elsevier.com/permissions

This book and the individual contributions contained in it are protected under copyright by the

Publisher (other than as may be noted herein)

Notices

Knowledge and best practice in this field are constantly changing As new research and

experience broaden our understanding, changes in research methods, professional practices,

or medical treatment may become necessary

Practitioners and researchers must always rely on their own experience and knowledge

in evaluating and using any information, methods, compounds, or experiments described

herein In using such information or methods they should be mindful of their own safety

and the safety of others, including parties for whom they have a professional responsibility

With respect to any drug or pharmaceutical products identified, readers are advised to

check the most current information provided (i) on procedures featured or (ii) by the

manufacturer of each product to be administered, to verify the recommended dose or

formula, the method and duration of administration, and contraindications It is the

responsibility of practitioners, relying on their own experience and knowledge of their

patients, to make diagnoses, to determine dosages and the best treatment for each individual

patient, and to take all appropriate safety precautions

To the fullest extent of the law, neither the Publisher nor the authors, contributors, or

editors, assume any liability for any injury and/or damage to persons or property as a matter

of products liability, negligence or otherwise, or from any use or operation of any methods,

products, instructions, or ideas contained in the material herein

Previous editions copyrighted 2009 by Saunders, an imprint of Elsevier Inc.; 1998 by Claudio

Ronco, MD, and Rinaldo Bellomo, MD

Library of Congress Cataloging-in-Publication Data

Names: Ronco, C (Claudio), 1951- editor | Bellomo, R (Rinaldo), 1956-editor | Kellum,

John A., editor | Ricci, Zaccaria, editor

Title: Critical care nephrology / editors, Claudio Ronco, Rinaldo Bellomo, John A Kellum,

Zaccaria Ricci

Other titles: Critical care nephrology (Ronco)

Description: Third edition | Philadelphia, PA : Elsevier, Inc., [2018] | Includes bibliographical

references and index

Identifiers: LCCN 2017004974 | ISBN 9780323449427 (hardcover : alk paper)

Subjects: | MESH: Kidney Diseases—therapy | Kidney Diseases—complications | Critical Care

Classification: LCC RC903 | NLM WJ 300 | DDC 616.6/1028—dc23 LC record available at

https://lccn.loc.gov/2017004974

Content Strategist: Nancy Anastasi Duffy

Content Development Specialist: Janice Galliard

Publishing Services Manager: Patricia Tannian

Project Manager: Stephanie Turza

Design Direction: Margaret Reid

Printed in the United States of America

Last digit is the print number: 9 8 7 6 5 4 3 2 1

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To my wife, Paola, for her love, patience and support.

To Federico, my dear son, now an esteemed colleague.

Claudio Ronco

To my wife, Debbie, for her patience, understanding, and support

To my daughter, Hilary, may she long continue to pursue excellence

and wisdom To both for giving my life meaning.

Rinaldo Bellomo

To my parents, John and Barbara, whose support and

encouragement make all things seem possible; to my wonderful wife, Nita, who keeps my feet on the ground; and to my children, Brianna and Alston, who have given me the greatest joys

I have ever known.

Zaccaria Ricci

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Contributors

Robert C Albright, Jr, MD

Associate Professor of Medicine

Chair and Consultant

Division of Nephrology and

Bronx, New York;

Director of Outpatient Dialysis and

Continuous Renal Replacement

Therapy

Beth Israel Medical Center

New York, New York

Maria Lucia Angelotti, MD

Excellence Centre for Research

Transfer and High Education for

the Development of DE NOVO

Renal Intensive Care Unit

Parma University Hospital

Parma, Italy

Nishkantha Arulkumaran, PhD

Lecturer, Intensive Care Medicine

Bloomsbury Institute of Intensive

Care Medicine

University College London

London, United Kingdom

Pierre Asfar, MD

Département de Réanimation Médicale et de Médecine Hyperbare

Centre Hospitalier Universitaire d’Angers

Laboratoire de Biologie Neurovasculaire et Mitochondriale Intégrée

Institut MitovascUniversité d’AngersAngers, France

Stephen R Ash, MD, FACP

Indiana University Health ArnettHemoCleanse Technologies, LLCAsh Access Technology

Samuele Ave, MD

Nuclear Medicine PhysicianDepartment of Nuclear MedicineSan Bortolo Hospital

Vicenza, Italy

Sean M Bagshaw, MD

Critical Care MedicineFaculty of Medicine and DentistryUniversity of Alberta

Edmonton, Alberta, Canada

Vasanthi Balaraman, MD

Division of NephrologyColumbia University Medical CenterNew York, New York

Ian Baldwin, RN, PhD, FACCCN

Austin HealthRMIT UniversityDeakin UniversityMelbourne, Australia

Joanne M Bargman, MD

Division of NephrologyUniversity Health NetworkUniversity of TorontoToronto, Ontario, Canada

Gina-Marie Barletta, MD

Pediatric Kidney Disease and Hypertension CentersPhoenix, Arizona

Jeffrey F Barletta, PharmD, FCCM

Professor and Vice Chair of Pharmacy PracticeMidwestern University, College of Pharmacy-Glendale

Glendale, Arizona

Shriganesh R Barnela, MD, DNB

DirectorNephron Kidney CareConsultant Interventional Nephrologist

United CIIGMA HospitalAurangabad, India

Hülya Bayır, MD

Professor of Critical Care Medicine, Environmental and Occupational Health

UPMC Endowed Chair in Critical Care Pediatric Research

University of PittsburghResearch Director and Associate Chief of Pediatric Critical Care Medicine

Children’s Hospital of PittsburghAssociate Director of Center for Free Radical and Antioxidant Health and Safar Center for Resuscitation Research

Pittsburgh, Pennsylvania

Monica Beaulieu, MD, FRCPC, MHA

Clinical Associate ProfessorUniversity of British ColumbiaHead, Division of NephrologyProvidence Health CareVancouver, British Columbia, Canada

Antonio Bellasi, MD

Department of Nephrology and Dialysis

S.Anna HospitalComo, Italy

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viii Contributors

Rinaldo Bellomo, MB BS (Hons),

MD, FRACP, FCICM, FAAHMS

Austin Hospital and Royal

Melbourne Hospital

Australian and New Zealand

Intensive Care Research Centre

School of Public Health and

Mount Sinai Hospital

New York, New York

Anesthesiology and Medicine

Vanderbilt University Medical Center

Hopital du Sacré-Coeur de Montréal

Montréal, Québec, Canada

Edmund Bourke, MD

Department of MedicineVeterans Administration Medical Center

Brooklyn, New York

George Braitberg, FACEM, FACMT

Professor of Emergency MedicineDirector of Emergency MedicineUniversity of MelbourneThe Royal Melbourne HospitalParkville, Victoria, Australia

Vicenza, ItalyDepartment of Medicine DIMEDUniversity of Padova Medical SchoolPadova, Italy

Stead Family University of Iowa Children’s Hospital

University of IowaIowa City, Iowa

Richard Bucala, MD, PhD

Department of Internal MedicineDepartment of PathologyYale University School of MedicineNew Haven, Connecticut

Renato Antunes Caires, MD

Sao Paulo State Cancer InstituteUniversity of Sao Paulo

Sao Paulo, Brazil

Pietro Caironi, MD

SCDU Anestesia e RianimazioneAzienda Ospedaliero-Universitaria San Luigi Gonzaga

Department of OncologyUniversity of TurinTurin, Italy

Roberta Camilla, MD

Nephrology Dialysis and Transplantation UnitRegina Margherita Children’s Hospital

Turin, Italy

Israel Campos, MD

Senior Research FellowRenal Research InstituteNew York, New York

Bernard Canaud, MD

Emeritus ProfessorMontpellier UniversityUFR Medicine

Montpellier, FranceChief Medical OfficerCentre of Excellence MedicalBad Homburg, Germany

Vincenzo Cantaluppi, MD

Associate Professor of NephrologyChief of Nephrology, Dialysis, and Kidney Transplantation UnitDepartment of Translational Medicine

University of Eastern PiedmontNovara, Italy

Maria P Martinez Cantarin, MD

Assistant Professor of MedicineDivision of Nephrology

Thomas Jefferson UniversityPhiladelphia, Pennsylvania

Giovambattista Capasso, MD, PhD, FERA

Department of NephrologyUniversity of Campania–Luigi Vanvitelli

Eleonora Carlesso, Dip Ing.

Dipartimento di Fisiopatologia Medico-Chirurgica e dei TrapiantiUniversità degli Studi di MilanoMilan, Italy

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Assistant Professor of Medicine

Department of Infectious Diseases

University of Nebraska Medical Center

Omaha, Nebraska

Jorge Cerda, MD

Department of Medicine

Albany Medical College

Albany, New York

Elliot Charen, MD

Department of Nephrology

Icahn School of Medicine

New York, New York

Lakhmir S Chawla, MD

Division of Intensive Care Medicine

Division of Nephrology

Department of Medicine

Veterans Affairs Medical Center

Washington, District of Columbia

Horng-Ruey Chua, MBBS, MMed(Int

Med), FRCP(Edin), FAMS, FASN

Division of Nephrology and Dialysis

University of Naples Federico II

Naples, Italy

Paola Ciceri, MD

Renal Division

Department of Health Sciences

San Paolo Hospital

University of Milan

Milan, Italy

Jacek Cieslak, MD, FRCPC

Nephrology ResidentDepartments of Internal Medicine and Nephrology

University of British ColumbiaVancouver, British Columbia, Canada

William R Clark, MD

Davidson School of Chemical Engineering

Purdue UniversityWest Lafayette, Indiana

Rolando Claure-Del Granado, MD, FASN

Universidad Mayor de San SimonSchool of Medicine–Hospital Obrero

#2Cochabamba, Bolivia

Ivan N Co, MD

Clinical Assistant ProfessorDepartment of Emergency Medicine and Internal Medicine

Division of Emergency Critical Care and Pulmonary Critical Care Medicine

University of MichiganAnn Arbor, Michigan

Fernanda Oliveira Coelho, MD, PhD

Sao Paulo, Brazil

Ferruccio Conte, MD

Renal DivisionDepartment of Health SciencesSan Paolo Hospital

University of MilanMilan, Italy

Milan, Italy

Elerson Carlos Costalonga, MD

Sao Paulo, Brazil

Maria Rosa Costanzo, MD, FACC, FAHA

Advocate Medical GroupMidwest Heart SpecialistsOak Brook, Illinois

Mario Cozzolino, MD

Carl H Cramer II, MD

Mayo Eugenio Litta Children’s Hospital

Mayo ClinicRochester, Minnesota

Jacques Creteur, MD, PhD

Department of Intensive CareErasme University HospitalUniversité Libre de BruxellesBrussels, Belgium

R John Crew, MD

Assistant Professor of Internal Medicine

Division of NephrologyColumbia University Medical CenterNew York, New York

Verônica Torres da Costa e Silva,

Andrew R Davies, MB, BS, FRACP

Deputy DirectorDepartment of Intensive Care,Alfred Hospital

Melbourne, Victoria, Australia

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x Contributors

Rohit D’Costa, FRACP, FCICM

The Royal Melbourne Hospital

Parkville, Victoria, Australia

Intensive Care Unit

Marc Jacquet Hospital

Amsterdam Cardiovascular Sciences

Amsterdam, the Netherlands

Camden, New Jersey

Lucia Del Vecchio, MD

Department of Nephrology and

Dialysis

Alessandro Manzoni Hospital

Lecco, Italy

Thomas A Depner, MD

Emeritus Professor of Medicine

Department of Internal Medicine

San Bortolo HospitalVicenza, Italy

Clifford S Deutschman, MS, MD, MCCM

Vice-Chair, Research, Department of Pediatrics

Professor of Pediatrics and Molecular MedicineHofstra–Northwell School of Medicine

New Hyde Park, New York;

ProfessorElmezzi Graduate School of Molecular MedicineFeinstein Institute for Medical Research

Manhasset, New York

Prasad Devarajan, MD

Louise M Williams Endowed ChairProfessor of Pediatrics and

Developmental BiologyDirector of Nephrology and Hypertension

Director, Pediatric Nephrology Fellowship Program

Co-Director, Office of Pediatric Clinical Fellowships

Medical Director, Stone CenterDirector, NIH Center of Excellence in Nephrology

CEO, Dialysis UnitCincinnati Children’s Hospital Medical Center

Biagio R Di Iorio, MD

Division of Nephrology and DialysisThe Hospital of Solofra Agostino Landolfi

Lucia Di Micco, MD

Division of Nephrology and DialysisThe Hospital of Solofra Agostino Landolfi

Solofra, Italy

Matteo Di Nardo, MD

Pediatric Intensive Care UnitDepartment of Emergency, Anesthesia, and Intensive Care (DEA-ARCO)

Bambino Gesù Children’s Hospital, IRCCS

Rome, Italy

Xiaoqiang Ding, MD, PhD

ProfessorDepartment of Internal MedicineFudan University

Director, Department of NephrologyZhongshan Hospital

Fudan UniversityShanghai, China

San Bortolo HospitalVicenza, Italy

Salvatore Di Somma, MD, PhD

Department of Medical-Surgical Sciences and Translational Medicine

University of Rome SapienzaRome, Italy

Kent Doi, MD, PhD

Department of Acute MedicineThe University of TokyoTokyo, Japan

David J Dries, MD

Division Medical DirectorHealthPartners Medical Group and Professor of Surgery

University of MinnesotaMinneapolis, Minnesota

Wilfred Druml, MD

Medical Department IIIDivision of NephrologyVienna General HospitalMedical University of ViennaVienna, Austria

Graeme Duke, MD, FCICM

Box Hill Hospital, Eastern HealthMelbourne, Australia

Indianapolis, Indiana

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Contributors xi

Devin Eckstein, DO

The Children’s Kidney Center of

New Jersey

Goryeb Children’s Hospital

Morristown, New Jersey

Research Unit VUmc Intensive Care

(REVIVE)

Francesca Elli, MD

Renal Division

Department of Health Sciences

San Paolo Hospital

Research Assistant Professor

Department of Critical Care

Medicine

Center for Critical Care Nephrology

The CRISMA Center

University of Pittsburgh School of

Cardiovascular Disease Program

Bioscience Discovery Institute and

Ann Arbor, Michigan

Christine Kinggaard Federspiel, MD

Departments of Medicine and Anesthesia

University of CaliforniaSan Francisco, CaliforniaDepartment of AnesthesiologyNordsjællands HospitalUniversity of CopenhagenCopenhagen, Denmark

Enrico Fiaccadori, MD, PhD

Renal Intensive Care UnitParma University HospitalParma, Italy

Nephrology, Dialysis, and Transplantation UnitUniversity of BariBari, Italy

Caleb Fisher, MD

Liver Intensive Care UnitInstitute of Liver StudiesKing College HospitalLondon, United Kingdom

Michael F Flessner, MD, PhD

Medical DirectorFrederick Community Action Agency

Guildford, United Kingdom

Claire Francoz, MD, PhD

Hepatology and Liver Intensive Care

Hospital BeaujonClichy, France

Craig French, MBBS, FCICM, FANZCA

Director of Intensive CareWestern Health

Clinical Associate ProfessorThe University of MelbourneParkville, Victoria, Australia

Dana Y Fuhrman, DO, MS

Center for Critical Care NephrologyDepartment of Critical Care Medicine

University of PittsburghPittsburgh, Pennsylvania

Giordano Fumagalli, MD

Nephrology and Dialysis UnitUSL Toscana Nord OvestVersilia Hospital

Lido di Camaiore, Italy

Miriam Galbusera, BiolSciD

Head, Unit of Platelet-Endothelial Cell Interaction

IRCCS–Istituto di Ricerche Farmacologiche Mario NegriBergamo, Italy

Maurizio Gallieni, MD

Nephrology and DialysisASST Santi Paolo e CarloDepartment of Biomedical and Clinical Sciences “Luigi Sacco”University of Milano

Milan, Italy

Hilary S Gammill, MD

Associate ProfessorDepartment of Obstetrics and Gynecology

University of WashingtonAffiliate InvestigatorFred Hutchinson Cancer Research Center

Seattle, Washington

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Dialysis and Transplantation

International Renal Research

University of British Columbia

Vancouver, British Columbia, Canada

Professor of Clinical Surgery

Surgical Director, Liver Transplant

Program

Division of HepatoBiliary

Surgery and Abdominal Organ

Transplantation

Keck School of Medicine

University of Southern California

Los Angeles, California

Christel Geradin, MD

Intensive Care Unit

Marc Jacquet Hospital

Melun, France

Loreto Gesualdo, MD, FERA

Nephrology, Dialysis, and

Director of Clinical Laboratory

Associate Professor of Clinical Medicine

Department of MedicineWeill Cornell Medical CollegeNew York, New York

Stuart L Goldstein, MD

Clark D West Endowed ChairDirector, Center for Acute Care Nephrology

Cincinnati Children’s Hospital Medical Center

Cincinnati, Ohio

Thomas A Golper, MD, FACP, FASN

Professor of MedicineDepartment of NephrologyVanderbilt University Medical CenterNashville, Tennessee

University of FoggiaFoggia, Italy

Giacomo Grasselli, MD

Dipartimento di AnestesiaRianimazione ed Emergenza UrgenzaFondazione IRCCS Ca’ Granda–

Ospedale Maggiore PoliclinicoMilan, Italy

A.B Johan Groeneveld, MD, PhD

(deceased)

Department of Intensive CareErasmus Medical CenterRotterdam, the Netherlands

Philippe Guerci, MD

Surgical Intensive Care UnitDepartment of Anesthesiology and Intensive Care Medicine

University Hospital of NancyNancy, France

Kyle J Gunnerson, MD, FCCM

Associate ProfessorDepartments of Emergency Medicine, Anesthesiology, and Internal Medicine

Chief, Division of Emergency Critical Care

Medical Director, Massey Family Foundation Emergency Critical Center (EC3)

Michigan Center for Integrative Research in Critical Care (MCIRCC)

University of Michigan Health System

Ann Arbor, Michigan

Nikolas Harbord, MD

Assistant Professor of MedicineDepartment of NephrologyIcahn School of MedicineNew York, New York

Lyndsay A Harshman, MD

University of Iowa Stead Family Department of PediatricsDivision of Pediatric Nephrology, Dialysis, and TransplantationIowa City, Iowa

Anthony J Hennessy, MB BCh, MRCPI

Senior RegistrarAnaesthesia and Intensive CareCork University HospitalCork, Ireland

Graham L Hill, MD, FRCS, FRACS, FACS

(deceased)

Emeritus Professor of SurgeryFaculty of Medical and Health Sciences

University of AucklandAuckland, New Zealand

Charles Hobson, MD, MHA

Department of Health Services Research, Management, and PolicyUniversity of Florida

Gainesville, Florida

Bernd Hohenstein, MD

Nephrological Center Villingen-SchwenningenFaculty of Medicine Carl Gustav Carus

Technische Universitat DresdenDresden, Germany

Patrick M Honoré, MD

Intensive Care Unit DepartmentUniversitair Ziekenhuis BrusselVrije Universiteit BrusselBrussels, Belgium

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Contributors xiii

Edward Horwitz, MD

MetroHealth Medical Center

Case Western Reserve University

School of Medicine

Cleveland, Ohio

Leila Hosseinian, MD

Department of Anesthesiology

Mount Sinai Hospital

New York, New York

Eric A.J Hoste, MD, PhD

Medicine

Ghent University Hospital

Ghent, Belgium

Ghent University, Ghent, Belgium

and Research Foundation–Flanders

Brussels, Belgium

Andrew A House, MD, MS, FRCPC,

FASN

Professor of Medicine

Chair/Chief Division of Nephrology

Schulich School of Medicine &

University of Michigan School of

Erasmus Medical Center

Erasmus University of Rotterdam

Rotterdam, the Netherlands

Stritch School of Medicine

Loyola University Chicago

Maywood, Illinois

Rita Jacobs, MD

Olivier Joannes-Boyau, MD

Department of Anesthesiology and Intensive Care II

University of BordeauxBordeaux, France

Michael Joannidis, MD

Professor of MedicineDivision of Intensive Care and Emergency Medicine

Department of Internal MedicineMedical University InnsbruckInnsbruck, Austria

Sandra L Kane-Gill, PharmD, MSc

Associate Professor of MedicineDepartment of Pharmacy and Therapeutics

Department of Critical Care Medicine

Lewis J Kaplan, MD, FACS, FCCM

Associate Professor of SurgeryPerelman School of Medicine, University of PennsylvaniaDivision of Trauma, Surgical Critical Care, and Emergency SurgerySection Chief, Surgical Critical CareCorporal Michael J Crescenz VA Medical Center

Rochester, Minnesota

Nevin Katz, MD

Division of Cardiac SurgeryJohns Hopkins UniversityBaltimore, Maryland

Ramesh Khanna, MD

Karl D Nolph, MD Chair in Nephrology

Professor of MedicineDirector

Division of NephrologyUniversity of Missouri-Columbia,Columbia, Missouri

Joshua D King, MD

Division of NephrologyUniversity of Virginia Health SystemCharlottesville, Virginia

Christopher J Kirwan, MD

William Harvey InstituteBarts and the London School of Medicine and DentistryQueen Mary University of LondonAdult Critical Care Unit and Department of Renal Medicine and Transplantation

The Royal London HospitalBarts Health NHS TrustLondon, United Kingdom

Joseph E Kiss, MD

Professor of MedicineUniversity of PittsburghPittsburgh, Pennsylvania

David Klein, MD, MBA

Staff PhysicianDepartment of Critical Care

St Michael’s HospitalAssistant Professor of Medicine and Public Health

University of TorontoScientist

Li Ka Shing Knowledge InstituteToronto, Ontario, Canada

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xiv Contributors

Peter Kotanko, MD, FASN

Research Director

Renal Research Institute

Adjunct Professor of Medicine

Jan Willem Kuiper, MD, PhD

Intensive Care and Pediatric Surgery

Erasms MC–Sophia Children’s

Department of Clinical and Experimental Biomedical SciencesUniversity of Florence

Joannie Lefebvre, MD

Assistant Professor of ClinicDepartment of MedicineNephrology DivisionHôpital Maisonneuve-RosemontUniversité de Montréal

Montréal, Québec, Canada

Paolo Lentini, MD, PhD

Department of Nephrology

St Bassiano HospitalBassano del Grappa, Italy

Hélène Leray-Moragués, MD

Department of NephrologyLapeyronie University HospitalMontpellier, France

Vancouver, British Columbia, Canada

Susie Q Lew, MD

Department of MedicineGeorge Washington UniversityWashington, District of Columbia

Helen Liapis, MD

Senior ConsultantArkana LaboratoriesLittle Rock, Arkansas

Kathleen D Liu, MD, PhD

Departments of Medicine and Anesthesia

University of CaliforniaSan Francisco, California

Sergio Livigni, MD

Director, Intensive Care UnitSan Giovanni Bosco HospitalTorino, Italy

Francesco Locatelli, MD

Department of Nephrology and Dialysis

Manzoni HospitalLecco, Italy

Vicenza, Italy

Jian-Da Lu, MD

Department of NephrologyHuashan Hospital

Fudan UniversityShanghai, China

Renhua Lu, MD

Associate Chief PhysicianDepartment of NephrologySchool of MedicineRenji HospitalShanghai Jiao Tong UniversityShanghai, China

Nicholas Lysak, MD

Department of SurgeryUniversity of FloridaGainesville, Florida

University of California, Davis School of Medicine

Sacramento, California

François Madore, MD

Professor of MedicineUniversité de MontréalMontréal, Québec, Canada

Linda L Maerz, MD

Department of SurgeryYale University School of MedicineNew Haven, Connecticut

Matthew J Maiden, MD, PhD

ConsultantIntensive Care UnitRoyal Adelaide HospitalAdelaide, South Australia, Australia;University Hospital Geelong

Geelong, Victoria, Australia

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Ravindra L Mehta, MD, FASN

University of California San DiegoSan Diego, California

Caterina Mele, PhD

IRCCS–Istituto di Ricerche Farmacologiche Mario NegriClinical Research Center for Rare Diseases Aldo e Cele DaccòBergamo, Italy

Aggregated Professor of NephrologyUniversity of Pisa

Jean-Yves Meuwly, MD

Associate ProfessorRadiology DepartmentCentre Hospitalier et Universitaire Vaudois (CHUV)

Madhukar Misra, MD, FRCP(UK), FASN, FACP

Professor of Clinical MedicineUniversity of Missouri–ColumbiaColumbia, Missouri

Paraish S Misra, MD

Division of NephrologyUniversity of TorontoToronto, Ontario, Canada

Barry A Mizock, MD

Department of MedicineUniversity of Illinois at ChicagoChicago, Illinois

Jwalant R Modi, MBBS

Division of NephrologyIndiana University School of Medicine

Gilbert Moeckel, MD, PhD

Department of PathologyYale University School of MedicineNew Haven, Connecticut

Bruce A Molitoris, MD

Distinguished Professor of Medicine and Integrative and Cellular Physiology

Division of NephrologyIndiana University School of Medicine

Santo Morabito, MD

Hemodialysis UnitDepartment of Nephrology and Urology

Umberto I Hospital, SapienzaUniversity of Rome

Rome, Italy

Roberto Pozzi Mucelli, MD

ChiefDepartment of RadiologyUniversity of VeronaVerona, Italy

Patrick T Murray, MD, FASN, FRCPI, FJFICMI

Professor of MedicineSchool of Medicine and Medical Science

University College DublinDublin, Ireland

Raghavan Murugan, MD

Center for Critical Care NephrologyDepartment of Critical Care Medicine

University of Pittsburgh School of Medicine

Pittsburgh, Pennsylvania

Mitra K Nadim, MD

Professor of Clinical MedicineDivision of Nephrology and Hypertension

Keck School of MedicineUniversity of Southern CaliforniaLos Angeles, California

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xvi Contributors

Devika Nair, MD

Chief Nephrology Fellow

Nashville, Tennessee

Federico Nalesso, MD, PhD

Department of Nephrology, Dialysis

and Transplantation

Institute of Vicenza (IRRIV)

Vicenza, Italy

Mauro Neri, MD

Department of Nephrology, Dialysis

and Transplantation

Department of Management and

Engineering

University of Padova

Vicenza, Italy

Trung C Nguyen, MD

Associate Professor of Pediatrics

Baylor College of Medicine

Texas Children’s Hospital

Farmacologiche Mario Negri

Clinical Research Center for Rare

Diseases Aldo e Cele Daccò

Senior Associate Consultant

Divisions of Infectious Diseases

and Pulmonary and Critical Care

Medicine

Mayo Clinic College of Medicine

Rochester, Minnesota

Mark Douglas Okusa, MD

Division of Nephrology and Center

of Immunity and Regenerative

Providence, Rhode Island

Helen Ingrid Opdam, FRACP, FCICM

The Austin HospitalHeidelberg, Victoria, Australia

Guy’s and St Thomas’ Foundation Hospital

London, United Kingdom

Emerenziana Ottaviano, MD

Heleen M Oudemans-van Straaten,

MD, PhD

Department of Adult Intensive Care

VU University Medical CentreAmsterdam, the Netherlands

Christian Overgaard-Steensen, MD, PhD

Department of Intensive CareRigshospitalet

University of PadovaPadova, Italy

Vincenzo Panichi, MD

Nephrology and Dialysis UnitUSL Toscana Nord OvestVersilia Hospital

Lido di Camaiore, Italy

Priyanka Parameswaran, BS

Research AssociateNephrology and HypertensionCincinnati Children’s Hospital Medical Center

Cincinnati, Ohio

Samir S Patel, MD

The Veterans Affairs Medical CenterGeorge Washington University Medical Center

Washington, District of Columbia

ASUIUDDepartment of MedicineUniversity of UdineUdine, Italy

Sadudee Peerapornratana, MD

Division of NephrologyDepartment of MedicineFaculty of MedicineChulalongkorn UniversityKing Chulalongkorn Memorial Hospital

Bangkok, Thailand

Paolo Pelosi, MD

IRCCS AOU San Martino–ISTDepartment of Surgical Sciences and Integrated Diagnostics

University of GenoaGenoa, Italy

Zhi-Yong Peng, MD, PhD

Department of Critical Care Medicine

Zhongnan HospitalWuhan University School of Medicine

Wuhan, China

Norberto Perico, MD

IRCCS–Istituto di Ricerche Farmacologiche Mario NegriClinical Research Center for Rare Diseases Aldo e Cele DaccòBergamo, Italy

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Rianimazione ed Emergenza Urgenza

Fondazione IRCCS Ca’ Granda–

Ospedale Maggiore Policlinico

Dipartimento di Fisiopatologia

Medico-Chirurgica e dei Trapianti

Università degli Studi di Milano

Phuong-Chi Pham, MD, FASN

Chief, Division of Nephrology and

Hypertension

Nephrology Fellowship Training

Program Director

Olive View-UCLA Medical Center

Clinical Professor of Medicine

David Geffen School of Medicine at

UCLA

Sylmar, California

Phuong-Thu Pham, MD, FASN

Clinical Professor of Medicine

Director of Outpatient Services

Kidney Transplant Program

Department of Medicine, Nephrology

Division

David Geffen School of Medicine at

UCLA

Richard K.S Phoon, FRACP

Centre for Transplantation and

Centre Hospitalier Universitaire d’Angers

Angers, France

Valentina Pistolesi, MD, PhD

Hemodialysis UnitDepartment of Nephrology and Urology

Umberto I Hospital, SapienzaUniversity of Rome

Rome, Italy

Lindsay D Plank, DPhil, MSc

Associate ProfessorDepartment of SurgeryFaculty of Medical and Health Sciences

University of AucklandAuckland, New Zealand

Frans B Plötz, MD, PhD

Department of PediatricsTergooi Hospital

Blaricum, the Netherlands

Manuel Alfredo Podestá, MD

Resident in NephrologyUniversity of MilanMilan, ItalyASST Papa Giovanni XXIIIBergamo, Italy

Camillo Porta, MD

Medical OncologyIRCCS San Matteo University Hospital FoundationPavia, Italy

Marco Pozzato, MD

AKI Team LeaderNephrology and Dialysis UnitSan Giovanni Bosco HospitalTorino, Italy

The Royal London HospitalBarts Health NHS TrustLondon, United Kingdom

Zudin A Puthucheary, MD

Critical Care ConsultantRoyal Brompton HospitalLondon, United Kingdom

Camden, New Jersey

Jai Radhakrishnan, MD

Professor of MedicineDivision of NephrologyDepartment of MedicineColumbia University Medical CenterAssociate Division Chief for Clinical Affairs

Division of NephrologyNew York Presbyterian HospitalNew York, New York

Ranistha Ratanarat, MD

FellowDepartment of Nephrology, Dialysis and Transplantation

San Bortolo HospitalVicenza, ItalyInstructorDepartment of MedicineFaculty of Medicine Siriraj HospitalMahidol University

Bangkok, Thailand

Trang 17

xviii Contributors

Giuseppe Remuzzi, MD

IRCCS–Istituto di Ricerche

Farmacologiche Mario Negri

Clinical Research Center for Rare

Diseases Aldo e Cele Daccò

Ranica, Bergamo, Italy

Unit of Nephrology and Dialysis

Azienda Socio-Sanitaria Territoriale

Papa Giovanni XXIII

Bergamo, Italy

Shelby Resnick, MD

Perelman School of Medicine,

University of Pennsylvania

Division of Trauma, Surgical Critical

Care and Emergency Surgery

Philadelphia, Pennsylvania

Oleksa G Rewa, MD

Critical Care Medicine

Faculty of Medicine and Dentistry

Pediatric Cardiac Intensive Care Unit

Bambino Gesù Children’s Hospital,

Chief, Acute Dialysis UnitClinical Hospital

Pontificia Universidad Católica de Chile

Santiago, Chile

Paola Romagnani, MD

Excellence Centre for ResearchTransfer and High Education for the Development of DE NOVO Therapies (DENOTHE)

Department of Clinical and Experimental Biomedical SciencesUniversity of Florence

Nephrology UnitMeyer’s Children’s University Hospital

Florence, Italy

Stefano Romagnoli, MD

Department of Cardiac and Vascular Anesthesia and Post-Surgical Intensive Care Unit

Careggi HospitalFlorence, Italy

Vicenza, Italy

Federico Ronco, MD

Interventional CardiologyCardiothoracic and Vascular Department

AULSS-3 SerenissimaVenezia and Mestre, Italy

Mitchell H Rosner, MD

Division of NephrologyUniversity of Virginia Health SystemCharlottesville, Virginia

Emanuele Rossetti, MD

Pediatric Intensive Care UnitDepartment of Emergency, Anesthesia and Intensive Care (DEA-ARCO)

Bambino Gesú Children’s Hospital, IRCCS

Rome, Italy

James A Russell, MD

Principal InvestigatorCentre for Heart Lung InnovationDivision of Critical Care Medicine

St Paul’s HospitalUniversity of British ColumbiaVancouver, British Columbia, Canada

Georges Saab, MD

MetroHealth Medical CenterAssociate Professor of MedicineCase Western Reserve University School of Medicine

Cleveland, Ohio

Alice Sabatino, MD, MSc

Renal Intensive Care UnitParma University HospitalParma, Italy

Sonali S Saboo, DMRD, DNB

DirectorNephron Kidney CareConsultant RadiologistUnited Ciigma HospitalAurangabad, India

Vicenza, Italy;

Institute of Life SciencesSant’Anna School of Advanced Studies

Pisa, Italy

Penny Lynn Sappington, MD

Associate ProfessorDepartment of Critical Care Medicine

Marco Sartori, PharmD, PhD

Pharmacology SectionInternational Renal Research Institute of Vicenza (IRRIV)Vicenza, Italy;

Department of Pharmaceutical and Pharmacological Science

University of PaduaPadua, Italy

Judy Savige, MD

Department of MedicineRoyal Melbourne HospitalUniversity of MelbourneMelbourne, Australia

Francesco Paolo Schena, MD

Emeritus Professor of NephrologyUniversity of Bari

Lausanne, Switzerland

Trang 18

Contributors xix

Pieter Schraverus, MD

Department of Anesthesiology

Research Unit VUmc Intensive Care

(REVIVE)

Wibke Schulte, MD

Department of Surgery

Yale University School of Medicine

New Haven, Connecticut

Division of Allergy, Pulmonary, and

Critical Care Medicine

Hypertension, and Transplantation

Columbia University Medical Center

New York, New York

Theodore M Sievers, PharmD

Clinical Transplant PharmacistRonald Reagan UCLA Medical Center

Edward D Siew, MD

Associate Professor of MedicineVanderbilt Center for Kidney Disease (VCKD) and Integrated Program for AKI (VIP-AKI)

Mervyn Singer, MD

Professor of Intensive Care MedicineBloomsbury Institute of Intensive Care Medicine

University College LondonLondon, United Kingdom

Loren E Smith, MD, PhD

Assistant Professor of AnesthesiologyVanderbilt University Medical CenterNashville, Tennessee

Sachin S Soni, MD, DNB

DirectorNephron Kidney CareConsultant Interventional Nephrologist

United Ciigma HospitalAurangabad, India

Mara Serrano Soto, MD

Department of Nephrology, Dialysis and Transplantation

International Renal Research Institute of Vicenza (IRRIV)San Bortolo Hospital

Vicenza, Italy;

Servicio de NefrologíaHospital Universitario Marqués de Valdecilla

Santander, Spain

Herbert D Spapen, MD

Nattachai Srisawat, MD

Division of NephrologyDepartment of MedicineFaculty of MedicineChulalongkorn UniversityKing Chulalongkorn Memorial Hospital

Ajay Srivastava, MD, FASN

Associate Professor of MedicineProgram Director, Nephrology Fellowship

Division of Nephrology, Kidney C.A.R.E Program

University of CincinnatiCincinnati, Ohio

Giovanni Stellin, MD

Professor of Cardiac SurgeryUnit of Pediatric and Congenital Cardiovascular SurgeryDepartment of Cardiac, Thoracic, and Vascular Sciences

University of PadovaPadova, Italy

Jordan M Symons, MD

Department of PediatricsUniversity of Washington School of Medicine

Division of NephrologySeattle Children’s HospitalSeattle, Washington

Balazs Szamosfalvi, MD

Clinical Associate Professor of Medicine

Division of NephrologyDepartment of Internal MedicineUniversity of Michigan

Ann Arbor, Michigan

Kian Bun Tai, MBChB, MRCP, FHKAM

Honorary Clinical Assistant Professor

Department of Medicine and Therapeutics

Chinese University of Hong KongAssociate Consultant

Department of MedicineAlice Ho Miu Ling Nethersole Hospital

Hong Kong, China

Unmesh V Takalkar, MS

Consultant SurgeonUnited Ciigma HospitalAssociate ProfessorSurgical OncologyGovernment Cancer HospitalAurangabad, India

Trang 19

Director, Division of Nephrology,

Kidney C.A.R.E Program

University of Cincinnati

Chief, Section of Nephrology

Cincinnati VA Medical Center

Division of Nephrology and Center

of Immunity and Regenerative

Intensive Care Unit

Jikei University school of Medicine

Tokyo, Japan

Ali Valika, MD, FACC

Advocate Medical Group—Midwest

Heart Specialists

Oak Brook, Illinois

Wim Van Biesen, MD, PhD

Jill Vanmassenhove, MD, PhD

Renal DivisionGhent University HospitalGhent, Belgium

Anton Verbine, MD

Department of NephrologyConemaugh Health SystemJohnstown, Pennsylvania

Vicenza, Italy;

Department of Health ScienceSection of Anesthesiology and Intensive Care

University of FlorenceDepartment of Anesthesiology and Intensive Care

Azienda Ospedaliero Universitaria Careggi

Christophe Vinsonneau, MD, MSc

Intensive Care UnitMarc Jacquet HospitalMelun, France

Grazia Maria Virzì, Bsc

Department of Nephrology, Dialysis and Transplantation

International Renal Research Institute of Vicenza (IRRIV)San Bortolo Hospital

Consultant NephrologistHospital Kuala LumpurKuala Lumpur, Malaysia

Li Van Vong, MD

Intensive Care UnitMarc Jacquet HospitalMelun, France

Peter A Ward, MD

Department of PathologyUniversity of Michigan Medical School

Ann Arbor, Michigan

Matthew A Weir, MD

Department of MedicineSchulich School of Medicine and Dentistry

Western UniversityLondon, Ontario, Canada

James Frank Winchester, MD

Professor of MedicineDepartment of NephrologyIcahn School of MedicineNew York, New York

Adrian Wong, PharmD, MPH

Fellow, Outcomes Research and Pharmacy Informatics

Division of General Internal Medicine and Primary CareBrigham and Women’s HospitalBoston, Massachusetts

Trang 20

Assistant Professor, Nephrology

Thomas Jefferson University

Honorary Clinical Professor

Department of Medicine and

Therapeutics

Chinese University of Hong Kong

Chief-of-Service and Consultant

Vicenza, Italy

Miriam Zacchia, MD, PhD

Department of NephrologyUniversity of Campania–Luigi Vanvitelli

Naples, Italy

Teena P Zachariah, MD

Division of NephrologyColumbia University Medical Center

New York, New York

Pierluigi Zanco, MD

DirectorDepartment of Nuclear MedicineOspedale San Bortolo–ULSS 8 Berica

Vicenza, Italy

Alberto Zanella, MD

Dipartimento di AnestesiaRianimazione ed Emergenza UrgenzaFondazione IRCCS Ca’ Granda–

Ospedale Maggiore PoliclinicoDipartimento di Fisiopatologia Medico-Chirurgica e dei TrapiantiUniversità degli Studi di MilanoMilan, Italy

Jose J Zaragoza, MD

Intensive Care UnitHospital EspañolMexico City, Mexico

Alexander Zarbock

Departments of Anesthesiology, Intensive Care, and Pain MedicineUniversity Hospital Münster

Münster, Germany

Marta Zaroccolo, MD

Nuclear Medicine PhysicianDepartment of Nuclear MedicineOspedale San Bortolo

Vicenza, Italy

Han Zhang, MD

Attending PhysicianDepartment of NephrologyZhongshan HospitalFudan UniversityShanghai, China

Andrea Zimmer, MD

Assistant ProfessorDivision of Infectious DiseasesUniversity of Nebraska Medical Center

Omaha, Nebraska

Trang 21

Preface

Critical care nephrology is a new discipline formally born

in 1998 from a group of scientists and physicians who

established its definition as a multidisciplinary branch of

medicine dealing with issues at the crossroad of intensive

care medicine and nephrology The discipline became

estab-lished thanks to a growing appreciation of the importance

of this field, an expanding body of laboratory and clinical

research in this area, editorials (C Ronco, R Bellomo:

Critical Care Nephrology: the time has come Nephrol Dial

Transplant, 13, 264-267, 1998), International Congresses

(First-, Second, and Third International Courses on Critical

Care Nephrology, Vicenza Italy, 1998-2001-2004 and 2007),

and the first dedicated textbook (Critical Care Nephrology,

Kluwer Academic Publishers, 1998) This book, unique in

its nature, reach, and content, was well received by the

scientific and clinical community Now, 20 years after the

first edition, we are pleased to present the third edition,

enriched, updated, and expanded to take into account the

very large body of work carried out in the 10 years since

the last edition

The unrelenting advance of medical progress opens

new areas of interest and opportunity Such areas must

be explored and explained by experts with appropriate

reference tools and information sources to help clinicians

practice at the very best level Thus, after much clinical and

experimental research experience in the field of critical care

medicine and nephrology, we have decided to undertake

the effort of producing a third and revised edition of a book

dealing with this subject Common guidelines,

standard-ized approaches, and appropriate literature dealing with a

multidisciplinary approach to kidney diseases in critically

ill patients are emerging and growing significantly Internists,

surgeons, critical care physicians, and nephrologists all

treat critically ill patients with acute kidney injury and

the multiple system organ dysfunction syndromes The

approach varies from hospital to hospital and often within

hospitals It depends on the structure of the institution, the

tradition of the medical school, the financial status of the

facility, and the heterogeneity of training and experience of

clinicians Doctors from different fields write notes without

searching for a common multidisciplinary approach to the

patient Often, they hardly meet at the bedside and various

prescriptions are made in absence of a common

decision-making process

A comprehensive review of the state of the art on this

matter is definitely needed in both academic and clinical

medicine Critical Care Nephrology should provide such a

comprehensive review It will inevitably become a useful

reference tool for both nephrologists and intensivists The

title Critical Care Nephrology has been chosen to stress the

aim of the book: to provide a comprehensive and state-of-the

art description and understanding of the problems related

to kidney diseases and blood purification in critically ill

patients This review includes the pathophysiological

foundations of major syndromes, the basis of laboratory

investigations pertinent to this field, clinical approaches to

complex patient management, interactions between renal

and other organ system failure, monitoring techniques,

therapeutic interventions, supportive treatments, new and

advanced blood purification technologies, and the principles

of management for various relevant derangements The

title is also intended to draw the reader’s attention to the multidisciplinary nature of this complex subject matter and to the need for maximal cooperation between experts

in intensive care and nephrology

The book focuses on key aspects of the basic sciences

as they pertain to this field Experimental research and evidence-based concepts are also discussed Then, all relevant clinical syndromes with particular attention to pathophysiology, diagnosis, and clinical care are treated Finally, diagnostic tools and the application of technology

to therapeutical strategies and future trends are detailed

Critical Care Nephrology deals with general information,

definitions of critical illness, epidemiology, monitoring and diagnostic procedures, pathophysiology of organ systems in relation to kidney function, concepts of renal physiological and pathological responses to various derangements, oxygen transport and cardiovascular adaptations, hemodynamic parameters, respiratory parameters, mechanical ventilation and cardiac support, and severity score parameters as they relate to the complex care of patients with kidney injury or the requirement of advanced blood purification technology This book is also devoted to all forms of acute kidney injury, with specific reference to intensive care patients Prerenal, renal, and postrenal acute kidney injury is discussed in terms of etiology, frequency, mechanisms, pathophysiology, tissue lesions, biopsy patterns, diagnostic procedures, and management The nature of the multiple organ dysfunction syndrome is discussed, with special emphasis on the impact

of different organs’ dysfunction and kidney injury Kidney function and acute kidney injury in patients with kidney, liver, and heart transplants are also discussed in detail, as is acute illness occurring in long-term hemodialysis patients Finally, issues related to special patients such as children, diabetics, and elderly subjects are carefully analyzed in a specific session offering an important reference to pediatric critical care nephrology specialists

Special emphasis has been placed on diagnosis and therapeutic interventions and treatment procedures The role and significance of novel biomarkers of acute kidney injury are discussed Different forms of extracorporeal organ support are discussed in detail, including liver, lung, and cardiac support Artificial renal support is conceived and discussed first in terms of preventive measures to avoid renal failure and then as supportive treatment to replace renal function in different conditions Thus, the use and pharmacokinetics of drugs in the critically ill patient are thoroughly explored Various forms of extracorporeal therapies are discussed in detail, including hemodialysis, hemofiltration, hemoperfusion, and extracorporeal membrane oxygenation Mechanical ventilation, mechanical cardiac support, and the total artificial heart are discussed in relation

to kidney function Recent advances in the therapy of the sepsis syndrome are presented, and new insights on future trends in terms of extracorporeal treatments are provided.Replacement of renal function by dialysis has been carried out for many years in both acute and chronic renal failure patients The use of continuous renal replacement techniques has permitted new achievements in the correction

of the metabolic and clinical derangements observed in critically ill patients Today, extracorporeal techniques seem

to display important beneficial effects that may overcome

Trang 22

xxiv Preface

the classic indications of urea removal and fluid regulation

For this reason, a series of new techniques is appearing on

the scene, with the specific aim of designing a treatment

suitable for patients with multiple organ failure Selective

removal of cytokines and pro-inflammatory mediators,

plasma adsorption, and other techniques have been used

in vitro, in animal models, and sometimes in patients There

is a need to summarize all the current experience in the

field and to deliver a comprehensive review of most of

the experimental and clinical work carried out so far We

believe this book achieves such a goal

The multidisciplinary nature of the subject and the

rapid evolution of the knowledge in the field make this

third revised edition necessary Because of its uniqueness,

we believe this book will become a “classic” in the field

as did its predecessor and will be an important reference

tool for nephrologists and intensive care specialists It is

no coincidence that the editors of the book are themselves

specialists in these particular fields and are strategically

located throughout the world

In conclusion, the aim of this book is to provide a

com-prehensive and educational review of the field of critical

care nephrology Critical Care Nephrology aims to create

a complete reference book for colleagues who are dealing

every day with critically ill patients suffering from kidney

diseases, electrolyte and metabolic imbalances, poisoning,

severe sepsis, major organ dysfunction, and other

pathologi-cal events that require a multidisciplinary approach, a deep

knowledge of extracorporeal organ support techniques, and

a deep understanding of human knowledge in this field

The book seeks to facilitate the process of developing common definitions and approaches to patient management

in nephrology and critical care medicine, so that physicians think the same way and speak the same language As such,

it aims to present a comprehensive review of the recent evolution of the indications, applications, and mechanisms

of function of the most recent extracorporeal techniques both for the treatment of acute renal failure and for the management of related disorders in the critically ill patient Given these premises, the book may also be helpful for residents, fellows, and advanced trainees in nephrology and critical care medicine, as well as for staff physicians and members of the academic and scientific community involved in practice and research in the field of critical care nephrology

We are grateful to all contributors who made this book possible and to Dr Anna Saccardo for her contribution to the book, her invaluable assistance to the management of chapters, and the continuous contact and support to the authors and editors We especially thank the editorial team

at Elsevier who managed the production of the book with great professionalism and enthusiasm We hope our readers will find that this effort has been worth it and sincerely hope that it will contribute to improving the care of acutely ill patients worldwide

Claudio Ronco Rinaldo Bellomo John A Kellum Zaccaria Ricci

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SECTION 1

Principles of Critical Care

CHAPTER 1

The Critically Ill Patient

Jean-Louis Vincent and Jacques Creteur

This chapter will:

1 Identify the key indicators of organ dysfunction used to

characterize “critically ill patients.”

2 Discuss key principles of management for critically ill

patients using the VIP rule

3 Highlight the need for individualized therapy guided by

appropriate monitoring

4 Describe critical illness as one part of a continuum of

healthcare

We often hear the term “critically ill,” but exactly how can

we define the critically ill patient? What characteristics

make a patient “critically ill”? Synonyms of the word

critically include dangerously, severely, gravely, profoundly,

and desperately Although these all stress the serious nature

of this condition, they do not really help define it In fact,

the key feature that makes a patient critically ill is essentially

the presence (or imminent risk) of acute organ dysfunction

Importantly, although many critically ill patients have a

“life-threatening” condition, this term, although widely

used in the context of critical illness, is not an essential

component of its definition For example, patients at risk

of developing acute renal failure may be critically ill, but

they do not necessarily have a life-threatening condition

because, with appropriate support, it is possible to survive

with no renal function

The critically ill patient may have a single or multiple

disease processes, and the state of critical illness is therefore

difficult to define For example, some complex patients

with mild acute respiratory distress syndrome (ARDS)

associated with septic shock resulting from peritonitis also

have secondary renal failure and several comorbidities,

e.g., complicated diabetes and chronic obstructive pulmonary

disease (COPD) Critically ill patients therefore are

character-ized usually by the types and severities of their organ

dysfunction(s), which are different in each patient and

influence treatments and outcomes In the following section

we will consider the key indicators of organ dysfunction

used to characterize critically ill patients before briefly

discussing some of the general aspects of management and

monitoring that are typically used in these patients and thus form part of their “critical illness” identity

ORGAN DYSFUNCTION Cardiovascular

A patient with cardiovascular dysfunction has ficient oxygen available to meet tissue requirements, thus leading to dysfunction of other organ systems Circulatory failure or shock can be classified according to the four key pathophysiologic mechanisms: hypovolemic, cardiogenic, obstructive, or distributive.1 Shock is recognized clinically

insuf-by the presence of hypotension (although this is sometimes subtle, especially in patients with a history of hypertension) and typically requires vasopressor therapy Importantly, however, shock is not just hypotension, and the tissue perfusion must be evaluated This can be accomplished

by using the three “windows” to look inside the body: skin perfusion, urine output, and mental status (typically obtundation, disorientation, confusion) An increase in blood lactate concentration above 2 mEq/L (or mmol/L) provides important confirmation of abnormal cellular oxygen metabolism

Arrhythmias are no longer considered such an important sign of cardiovascular dysfunction in the critically ill patient, because the excessive treatment of arrhythmias in the past was accompanied by more complications than benefits Tachycardia does remain an important sign, but patients should be evaluated carefully using an algorithm to deter-mine the underlying cause Tachycardia is usually present

to compensate for a low stroke volume (in the presence of hypovolemia, cardiac pump issues, or an obstruction in the cardiovascular system) or to generate a supranormal cardiac output (in sepsis or other inflammatory conditions

or in anemia or hypoxemia)

Respiratory

There are two types of respiratory failure: hypercapnic (typically related to chronic lung disease or central hypoven-tilation) and hypoxemic (e.g., in pneumonia or ARDS) In

Trang 24

2 Section 1 / Principles of Critical Care

estimation of the score can be altered by the tion of sedatives, but sedatives are much less widely used than in the past If a patient is sedated or anesthetized, the “assumed” GCS should be considered, i.e., the score that the patient would have had in the absence of these medications

administra-Hepatic

An increase in liver enzymes is not very specific for liver damage, because they also can be released by muscle Therefore, despite its many limitations, serum bilirubin concentration is still used as the primary test of liver dysfunction Hemolytic anemia is relatively rare but, if present, obviously should be considered in the interpretation

of bilirubin levels An increase in bilirubin levels occurs only late in the development of multiple organ failure but

is sometimes a good indicator of an undrained focus of sepsis

Gastrointestinal

Gastrointestinal dysfunction is unfortunately too difficult

to assess objectively Tolerance to feeding is difficult to quantify, as are diarrhea and abdominal bloating Intra-abdominal hypertension is an important, but uncommon, problem

Quantifying Organ Dysfunction

Given the limitations of assessing gastrointestinal function, the first six organ systems discussed above (cardiovascular, respiratory, renal, hematologic, neurologic, hepatic) are usually the systems that are taken into consideration when characterizing organ dysfunction in critically ill patients Dysfunction of each of these systems can be quantified using a SOFA score (Table 1.1).2Fig 1.1 presents a chart

of the likely pattern of organ dysfunction shown by the patient described at the beginning of the chapter

the absence of acute circulatory failure (i.e., when skin

perfusion is adequate), oxygen saturation, measured by

pulse oximetry (SpO2), reflects arterial oxygen saturation

(SaO2) and, therefore, arterial partial pressure of oxygen

(PaO2) However, it cannot differentiate the two types of

respiratory failure Even on room air, both conditions result

in a low PaO2 and thus in a decrease in SpO2 Arterial

blood gas analysis therefore will be necessary To avoid an

arterial puncture, venous blood gas analysis can be

per-formed, preferably from a central vein, to estimate PaCO2

(which is a few mm Hg less than the PvCO2)

Renal

Although sensitive markers of renal (dys)function have been

developed (including neutrophil gelatinase-associated

lipocalin [NGAL], kidney injury molecule-1, interleukin

[IL]-18, and cystatin C), serum creatinine concentrations

are still the most widely used indicator of renal function

Creatinine clearance often is not calculated in acute, rapidly

evolving conditions Obviously, oliguria is an important

sign of possible renal failure in patients with acute

circula-tory failure, because urine output may decrease before the

serum creatinine has time to increase

Hematologic

Anemia is so common in critically ill patients that it is not

even considered as hematologic dysfunction Rather, the

presence of coagulopathy is considered as the main

indica-tion of hematologic funcindica-tion Because the prothrombin time

can be altered in the presence of liver dysfunction and

during anticoagulant therapy, platelet count is the most

widely used marker of hematologic dysfunction

Neurologic

There is no better simple test of neurologic function

than the Glasgow coma scale (GCS) score Obviously, the

Dopamine > 5 or epinephrine ≤ 0.1

or norepinephrine

≤ 0.1*

Dopamine > 15 or epinephrine > 0.1

or norepinephrine

> 0.1*

Central Nervous System

Trang 25

Chapter 1 / The Critically Ill Patient 3

dysfunction, limiting the need to correct perfusion deficits with fluids alone

Importantly, vasopressors should not be withheld until sufficient fluids have been given, as it is important to prevent, or at least to limit the duration of, any episode of arterial hypotension Even if there is a response to fluids, this does not necessarily prevent administration of small doses of norepinephrine when the fluid balance becomes too positive, because edema is associated with poorer outcomes

Therefore the three VIP elements should be administered together rather than one after the other As the patient’s condition improves, the different components can be reduced

as necessary to maintain hemodynamic stability Indeed, the time factor is essential because patient requirements vary over time during the disease process Four phases are identifiable in the management of the critically ill patient: salvage, optimization, stabilization, and de-escalation (SOSD)1 (Fig 1.3) In the salvage phase, the aim is emergency

PRINCIPLES OF MANAGEMENT:

THE VIP RULE

The basic resuscitation guidelines for critically ill patients

are based on the VIP (ventilation, infusion, pump) rule

proposed by Max H Weil many years ago3 (Fig 1.2) Oxygen

therapy should be given almost systematically to all patients,

although hyperoxia should be avoided If a pulse oximetry

signal can be reliably obtained (in the absence of altered

cutaneous perfusion), the SpO2 should be maintained at

around 94% to 97% In the case of severe decompensation,

mechanical ventilation is needed Noninvasive ventilation

may be tried first and is more effective in hypercapnic than

in hypoxemic respiratory failure The indications for

endotracheal intubation are not very strict, and clinical

experience plays an important role in deciding when this

should be performed During mechanical ventilation, low

tidal volumes always should be used In the presence of

severe hypoxemia, extracorporeal membrane oxygenation

(ECMO) may be required

Fluid infusion is the basis for an increase in oxygen

delivery obtained by an increase in cardiac output through

the Frank-Starling relationship When the likely response

to fluids cannot be predicted, the basic clinical approach

is to perform a fluid challenge, i.e., to give a small amount

of fluid over a limited period of time while carefully

monitoring the patient’s response.4 If there is no evident

clinical benefit, the fluid infusion should be stopped without

delay Signs of fluid responsiveness, such as pulse pressure

variation or stroke volume variation, can sometimes help

to predict the response to fluids, but these are only reliable

in patients who are appropriately monitored and

mechani-cally ventilated These patients also need to be sedated (to

avoid any triggering of the respirator), and sedation is used

less frequently in the modern intensive care unit (ICU)

The set of circumstances necessary for correct application

of these tests is therefore infrequently met Passive leg raising

also can be used for this purpose but is not as simple as it

may appear; it requires beat-by-beat monitoring of cardiac

output to identify the transient hemodynamic changes

(monitoring changes in arterial pressure is insufficient.)

The third aspect, “pump,” refers to the use of vasoactive

agents Norepinephrine is now the vasopressor agent of

choice The place of vasopressin derivatives has not yet

been defined; although they may perhaps limit edema

formation,5 clinical benefit has not been demonstrated

Dobutamine can be added in the presence of myocardial

FIGURE 1.1 Possible pattern of organ dysfunction shown

by a patient with mild acute respiratory distress

syndrome associated with septic shock resulting from

peritonitis, secondary renal failure, and comorbid

diabetes and chronic obstructive pulmonary disease

Circulatory Blood pressure, lactate,

need for vasoactive agents

Respiratory SpO2, need for oxygen,

abnormal blood gases

Renal Creatinine, new biomarkers,

urine output

Hematologic Platelets,

PT, APTT

Neurologic Mental status,

Glasgow coma score

Hepatic Bilirubin

Normal Dysfunction Failure

FIGURE 1.2 The VIP (ventilation, infusion, pump) rule proposed by Max H Weil and colleagues.3 IV, Intravenous

The VIP rule

Ventilate Oxygen administration

FIGURE 1.3 The four phases in resuscitation management over time

DO 2 , Oxygen delivery Modified from Vincent and De Backer1

Salvage

Live-savingmeasures

Optimization

Provideoptimal

DO2

Stabilization

Provideorgan supportEnsure stability

De-escalationWean fromvasoactive agentsObtain a negativefluid balanceTime

Trang 26

with early mobilization also is initiated much earlier than before, as soon as is practical on the ICU, to limit ICU-acquired weakness; this is facilitated by the much less widespread use of sedation Patients may even be taken outside the hospital with their respirators

CONCLUSION

Critically ill patients can be of any size, shape, age, and background, but all have a serious degree (or risk) of acute organ dysfunction and require admission to an ICU for monitoring and treatment Their underlying conditions may

be varied, but the resulting critical illness conditions (e.g., sepsis, acute respiratory failure, acute renal failure) are similar, and all such patients should be cared for by expe-rienced intensivists ICUs have changed considerably over the years and are no longer the frightening places they once were, to be avoided at all costs, but rather just one period

of many in a patient’s disease trajectory Today, patients often prefer (more often a wish expressed by their families)

to stay in the ICU, knowing they are under close surveillance with appropriate staff to prevent complications and provide rapid appropriate treatment Evaluation of the critically ill patient is based primarily on the type and severity of organ dysfunction, but treatment clearly is not limited to organ support Rather, patient management should be based on

a clear understanding of underlying pathophysiologic alterations so that a rational, individualized approach to therapy can be established

Key Points

1 A critically ill patient can be defined by the ence of acute organ dysfunction and the need for intensive monitoring and management.

pres-2 The pattern and severity of dysfunction of six organ systems—cardiovascular, respiratory, neurologic, hematologic, renal, and hepatic—are used to characterize critically ill patients.

3 Initial resuscitation for all critically ill patients can be guided by the VIP (ventilator, infusion, pump) mnemonic, with adequate oxygenation, fluid therapy, and vasoactive support.

4 Management should be adapted according to the patient’s phase of illness—salvage, optimization, stabilization, de-escalation (SOSD)—and guided

by monitoring equipment adjusted to individual needs and status.

5 Early awareness of deteriorating patient condition

in the general floor, enabling rapid intervention and greater attention to the long-term complications

of critical illness, helps optimize outcomes.

A complete reference list can be found online at Expert

-Consult.com

resuscitation and correction of shock As such, a rapid fluid

bolus should be given and interventions to treat any obvious

underlying cause and support failing organs initiated In

the optimization phase, the patient remains

hemodynami-cally unstable but is no longer in immediate danger of

hypovolemia The important target during this phase is to

optimize and maintain adequate tissue perfusion and

oxygenation to prevent and limit (further) organ damage

Fluids and vasoactive agents should be administered

according to individual needs, reassessed on a regular basis

The patient must be monitored carefully during this

opti-mization phase (see the following section) In the

stabiliza-tion phase, fluids are administered to replace ongoing losses

and often vasopressor agents can be weaned In the

de-escalation phase, the aim is to remove any excess fluid by

spontaneous diuresis if possible or using ultrafiltration or

diuretics if necessary

MONITORING SYSTEMS

Many large clinical trials have demonstrated that simple,

pragmatic protocols do not work in critically ill patients

Targeting a higher or a lower arterial pressure, a supranormal

cardiac output or a central venous oxygen saturation (ScvO2)

above a given value does not improve outcomes Rather,

treatment should be individualized according to each

patient’s needs and clinical response However, this approach

requires some form of monitoring Although all critically

ill patients therefore have some form of monitoring in situ,

the type and nature of such monitoring will depend, of

course, on the individual patient’s underlying disease

process(es) and clinical status and will vary during the

course of the ICU stay as the patient’s condition evolves

Local availability and physician preferences also affect the

types of monitoring used

Use of the pulmonary artery catheter has decreased

considerably in recent years, primarily because of the

development of echocardiographic techniques, but invasive

monitoring is still used Arterial catheters are needed for

accurate, continuous arterial pressure monitoring and

central venous catheters for monitoring of central venous

pressure to evaluate the response to therapy and the ScvO2

in complex cases In the future, we are likely to see more

patients with microcirculatory monitoring to assess ongoing

tissue oxygenation and perfusion

THE ICU STAY AS PART OF A TRAJECTORY

In the past, the ICU stay was a separate, detached event,

with patients being admitted when critically ill and

dis-charged when intensive care was no longer necessary Little

attention was paid to pre- or post-ICU care More recently,

the approach to critical illness has changed, and it is seen

much more as just one portion of the ongoing disease

trajec-tory ICU teams now are encouraged to leave the ICU to

evaluate patients on the floor before they deteriorate to

such an extent that ICU admission becomes a necessity

and also to follow up with patients after their ICU stay to

ensure their condition continues to improve Revalidation

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Chapter 1 / The Critically Ill Patient 4.e1

References

1 Vincent JL, De Backer D Circulatory shock N Engl J Med.

2013;369:1726-1734

2 Vincent JL, Moreno R, Takala J, et al The SOFA (Sepsis-related

Organ Failure Assessment) score to describe organ dysfunction/

failure On behalf of the Working Group on Sepsis-Related

Problems of the European Society of Intensive Care Medicine

Intensive Care Med 1996;22:707-710.

3 Weil MH, Shubin H The “VIP” approach to the bedside

manage-ment of shock JAMA 1969;207:337-340.

4 Vincent JL, Weil MH Fluid challenge revisited Crit Care Med.

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Chapter 2 / The Pathophysiologic Foundations of Critical Care 5

This chapter will:

1 Help the reader understand the philosophy behind using

dynamic real-time physiologic assessment in the

manage-ment of the critically ill, by noting the dynamic interactions

among disease process, physiologic reserve and therapy

2 Categorize critically ill patients’ disease processes into

discrete categories that allow for a more focused diagnostic

and therapeutic approach to care

PRINCIPLES

Increasingly patients are admitted to the hospital only

to receive emergency care of an acute condition, such as

trauma, hollow viscus perforation, myocardial infarction,

septic shock, and acute respiratory failure, or for a limited

number of elective procedures, such as invasive

diagnos-tic tests (angiograms), surgery, and high-risk therapies

Furthermore, the total hospitalization time and length of

stay in an intensive care setting are decreasing, resulting

in a greater degree of disease acuity in all centers of the

hospital Thus the principles of acute care medicine, which

reflect issues of simultaneous global assessment and both

nonspecific and personalized treatment of several related

or modifying pathologic and adaptive processes, transcend

any geographic area in the hospital Furthermore, basic

principles of management of patients with acute illness

encompass triage, selection of appropriate diagnostic and

therapeutic strategies by balancing risk-benefit issues and

the patient care, and healthcare cost of knowledge These

decisions often cross numerous boundaries among medical

and surgical specialties The acute care physician, once

relegated to serve in the intensive care unit, operating

theater, or emergency department, now sees a greater

role in the overall management of the acute hospitalized

patient The principles that underlie management of most

conditions requiring acute treatments within the hospital

setting, whether unexpected emergencies or the result of

therapies such as cardiac surgery, organ transplantation,

or bone marrow suppression, share a common basis of

thought and action, which forms the central theme of acute

care medicine

Initial stabilization with the goal of sustaining tissue

viability and preventing further organ injury, followed by

a focused diagnostic and therapeutic effort to correct the

key physiologic derangements, represent the primary initial

goals of acute care medicine However, to attain these goals

it is necessary for the caregiver to have a broad knowledge

base in the physiology, pathophysiology, and effect of

therapies on all organ systems to provide effective care of

the acutely ill patient Furthermore, if efficient healthcare

delivery is to be given to a population of acutely ill patients, realistic and appropriate guidelines must be developed in the hospital regarding scheduling of elective admissions, use of expensive and limited diagnostic and therapeutic resources, and a realistic method of continually monitoring their use to optimize patient care without excessive waste

By focusing diagnostic and treatment efforts on the most effective areas of investigation and management while limiting care to treatable and preventable causes, these efforts should result in efficient and effective use of limited healthcare resources and provide the greatest overall benefit

to the patients and society we serve

One of the fundamental pillars of this approach is the use of knowledge of the pathophysiologic processes causing disease in a specific patient and how to monitor disease severity and response to treatment and time

APPLIED PHYSIOLOGY AT THE BEDSIDE

The body is an amazing organism that adapts to changes

in external stress while maintaining adequate basal stasis within and among organs The primary function of the cardiorespiratory unit is to deliver adequate amounts

homeo-of oxygen (O2) and nutrients to the tissues to allow normal organ-system function while removing metabolic waste and respiration-generated carbon dioxide (CO2) Within this construct, the functionality of these systems has much metabolic reserve, because maximal metabolic demand rarely is required, and if maximal performance is required, then it is only for brief periods of time For example, in healthy young subjects maximum voluntary ventilation, maximal negative inspiratory pressure, maximal cardiac output (CO), and maximal oxygen delivery (DO2) exceed basal metabolic demands by 10- to 30-fold

As baseline organ system function decreases because of either primary organ functional loss as a result of injury

or age-related atrophy, the host can sustain basal function Because increased work by less tissue to achieve the overall good is required, each organ system eventually will display performance characteristics approaching severe metabolic demands For the cardiovascular system this manifests as first a greater increase in heart rate for minor exercise and then to resting tachycardia and increased vasomotor tone; for the respiratory system, tachypnea; for the kidneys, impaired concentration and salt wasting Importantly, the phenotype observed at the bedside is not that of a primary pathologic process, such as hemorrhage, infection, or infarction, but the host’s response to these pathologic processes to maintain homeostasis This intrinsic homeo-static process, mediated through both systemic sympathetic response and local adaptive cellular mechanisms, is very good for the host, because it allows for survival as organ system dysfunction progresses Without this self-correcting

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as an oncotic filter, whereas the tight junctions of the vascular endothelium function as the hydrostatic filters, allowing a dynamic equilibrium of blood volume to be created All of these systems are innervated by autonomic sympathetic and parasympathetic efferent and afferent nerves that can locally or systemically alter tone and contractility Increased sympathetic tone not only increases vasomotor tone and contractility but also causes tachycardia, a cardinal sign of circulatory stress

The actual effective circulating blood volume, that amount needed to create an effective pressure gradient to sustain venous return despite markedly changing metabolic and physical demand, is highly variable and can change

in seconds to meet those demands or induce cardiovascular collapse The body regulates the effective circulating blood volume by altering blood flow distribution among various tissues with varying degrees of stressed and unstressed venous capacitance and varying degrees of resistance to venous return For example, the mesenteric circulation (gut) has a high unstressed volume owing to the large potential capillary and venular space and a high output resistance

as all blood must flow through a second organ, the liver, before reaching the right heart Thus, for the same total blood volume, if more blood were shifted into the mesenteric circulation, all else being equal, the mean systemic pressure would decrease and the resistance to venous return would increase; thus for the same right atrial pressure, cardiac output would decrease Similarly, by increasing sympathetic tone, thus diverting blood away from the gut while simul-taneously increasing vascular tone and myocardial contractil-ity, cardiac output will increase and right atrial pressure will decrease for the same blood volume

Cardiac function has two primary roles The first is to deliver all the blood each ventricle received with each heart beat so as not to allow filling pressure to raise while simultaneously sustaining an adequate enough output pressure to allow for blood flow autoregulation Accordingly, because right atrial pressure is the back pressure to venous return, normal subjects have a right atrial pressure approxi-mating zero to minimize any impediment to venous return Heart failure, for its part, defines the filling pressure required

to create a given stroke volume and their maximal limits Furthermore, if severe pump failure develops, the left ventricle is no longer able to generate high systolic pressure while simultaneously requiring a higher filling pressure promoting hydrostatic pulmonary edema, the two hallmark signs of cardiogenic shock The reason why humans have such a high mean arterial pressure is to force blood flow not into organs but to all those individual vascular beds

to autoregulate their own local blood flow based on their own local metabolic demands The arterial circuit is composed of a relatively stiff central capacitor comprising the aorta and the arteries serially linked to distal high resistant arteriole and their associated precapillary sphinc-ters With the exception of the kidney and lung, local metabolic demand defines local end-organ arterial tone If metabolic demand increases, as with feeding/digestion, then the mesenteric arterioles dilate locally and inflow to those tissues increases Arterial pressure is only relevant

as it allows for blood flow regulation Systemic hypotension abolishes autoregulation and is the primary rationale for the defense of blood pressure during the acute phase of resuscitation from circulatory shock Thus right atrial pressure, effective circulating blood volume arterial tone, and cardiac contractility are intimately intertwined These points can be described by two relations: (1) the relation between cardiac output and dynamic changes in right atrial pressure as blood volume and cardiac contractility vary

internal system present, the host could not respond rapidly

to external metabolic demands, such as increased exercise,

eating, or environmental excess heat Regrettably for the

bedside clinician, such homeostatic mechanisms mask organ

system dysfunction until it is advanced, because the body

tends to sustain function as long as possible before

deteriorat-ing Deterioration often reflects a terminal event Thus

waiting for deterioration to occur before treating a patient

at risk for such deterioration is to wait too long, because

organ failure reflects failure of host defense homeostasis

Patients manifest unique signs and symptoms as a

func-tion of their baseline physiologic reserve and the magnitude

of the stress; failure of these compensatory mechanisms

results in external manifestations of organ failure For the

circulation, when sympathetic tone increase can no longer

sustain adequate arterial pressure and hypotension develops,

there must be associated decreases in vital organ blood

flow Thus hypotension represents a failure of host defense

homeostasis and, if sustained even for short periods of

time, will cause ischemia-related end organ injury and, if

sustained, death However, normotension does not equate

to normal cardiovascular function Thus an essential part

of the assessment and management of critically ill patients

is the continuous assessment and titration of support based

upon their specific status and response.1

BASICS OF CARDIOVASCULAR PHYSIOLOGY

Because circulatory shock is a central aspect of most forms

of critical illness, understanding basic principles of

car-diovascular physiology is essential to the assessment and

management of the critically ill patient Clearly, all aspects

of the patient, including neurologic control, gas exchange

and ventilation, renal solute clearance, gut substrate

absorp-tion, hepatic and reticuloendothelial clearance, immune

function and metabolic support, and appropriate endocrine

function are essential vital components of body homeostasis

Still, in the resuscitation of the critically ill patient, if blood

flow of oxygenated blood to the tissues at an adequate

perfusion pressure is not achieved, then perfusion-associated

organ injury will develop and all other measures will be

meaningless Thus a central tenet in acute resuscitation is

reflected in restoring cardiovascular homeostasis Indeed,

basal organ system function and its reserve to meet increased

metabolic demand define health and disease and the patient’s

ability to respond to therapy The manner by which the

bedside clinician infers the patient’s physiologic state is

by inspection, examination, and the use of various

hemo-dynamic monitoring approaches that quantify specific

physiologic parameters, such as blood pressure, cardiac

output, and tissue perfusion

The cardiovascular system is composed of blood vessels,

circulating blood volume, and two hydraulic pumps that

work collectively to meet the immediate metabolic demands

of the body Axiomatically, the heart can pump out only

what blood it receives; thus the primary determinant of

cardiac output is the rate of venous blood flow back to the

heart, referred to as venous return The left ventricle provides

the hydraulic pressure necessary to sustain a high central

arterial pressure essential to allow for the control of blood

flow distribution among the various vascular beds and to

supply in the steady state a higher mean systemic pressure

than right atrial pressure to allow blood flow back to the

right ventricle to be unimpeded The total circulating blood

volume remains relatively stable because the vascular

endothelial lining, referred to as the glycocalyx, functions

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Chapter 2 / The Pathophysiologic Foundations of Critical Care 7(Fig 2.1) and (2) the relation between left ventricular stroke

volume and mean arterial pressure as cardiac contractility

varies (Fig 2.2), arterial tone varies (Fig 2.3) or end-diastolic

volume varies (Fig 2.4)

From this brief overview, we can come up with a few

relevant conclusions (Box 2.1) First, tachycardia is a

nonspecific sign of stress and should not be ignored, even

if all other aspects of the patient seem adequate What

stress is causing the tachycardia must be discovered and, if

the result of a pathologic process (e.g., hypovolemia, heart

failure, vascular obstruction, reactive from hypovolemia),

treated Second, systemic arterial hypotension is a medical

emergency because it reflects loss of normal homeostasis

Hypotension must be associated with loss of autoregulation

of blood flow distribution, and this usually is associated with vital tissue (e.g., heart, kidney, and brain) hypoperfusion Third, there is no “normal” cardiac output Cardiac output

is an adaptive hemodynamic value that varies as metabolic demand varies Often significant changes in metabolic demand can occur without obvious external signs of change Thus global blood flow values must be targeted to organ

FIGURE 2.1 Theoretical relationship between steady state cardiac

output and right atrial pressure (Pra) across varying right atrial

pressures as total blood volume increases and contractility decreases

Note that for any given blood volume and contractility, there exists

only one right atrial pressure-cardiac output solution possible,

referred to as the equilibrium point

C Volume infusion

or fluid retention

Relation between contractility and right atrial pressure

FIGURE 2.2 Theoretical relationship between mean arterial pressure

and left ventricular stroke volume at a constant left ventricular

end-diastolic volume, as left ventricular stroke volume is varied

over varying levels of arterial vasomotor tone, quantified as arterial

elastance (Ea) On the same diagram is the relationship between

left ventricular stroke volume and mean arterial pressure as mean

arterial pressure is varied Increases in arterial tone result in greater

increases in pressure for the same increase in stroke volume as

seen when arterial tone is less Note that as arterial tone increases

(increased afterload), left ventricular stroke volume must decrease

Ventriculo arterial coupling effect of changes in E a

as left ventricular stroke volume is varied Increases in cardiac contractility result in greater increases in stroke volume for the same arterial tone Note that as cardiac contractility increases, left ventricular stroke volume and mean arterial pressure must increase

Ventriculo arterial coupling

Decreased Ees

FIGURE 2.4 Theoretical relationship between mean arterial pressure and left ventricular stroke volume as left ventricular end-diastolic volume (EDV) is varied On the same diagram is the relationship between left ventricular stroke volume and mean arterial pressure

as mean arterial pressure is varied Increases in left ventricular end-diastolic volume (preload) result in matched increases in mean arterial pressure and left ventricular stroke volume, similar to that seen by isolated increases in cardiac contractility

Ventriculo arterial coupling effect of changes in EDV

Decreased EDV

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adequate ventilation and oxygenation, intravascular fluid infusions if hypovolemia and decreased effective circulating blood volume are presumed, and if hypotension persists, adding vasopressors to support arterial pressure Within this context, cardiac output is important only to sustain

an adequate organ perfusion pressure Although the old mean arterial pressure must be personalized, based on prior known values, especially if the patient has preexisting hypertension, an initial mean arterial pressure target of

thresh-65 mm Hg is reasonable Similarly, respiratory efforts to keep arterial oxygen saturation above 88%, with adequate ventilation, is also indicated Clearly, if there are any life-taking ongoing processes, such as massive hemorrhage, severe trauma, acute myocardial infarction, or acute intraabdominal processes, emergent plans must be made during this time to definitively address these individual processes Realistically, these minimal goals should be established within the first 30 to 60 minutes of care.Once patients have a viable blood pressure, they are essentially not dying from hypoperfusion of the heart and the brain, but resuscitation has only just begun At this point, the focus turns to reversing the primary processes causing the initial cardiorespiratory insufficiency while simultaneously optimizing cardiac output to sustain adequate organ blood flow This phase of care focuses on assessment

of end-organ function and identifying and treating any reversible causes of shock Because there is no “normal” cardiac output, knowing a specific value does little to aid

in optimization interval unless its value is at the extremes

of high or low Changes in cardiac output in response to resuscitative therapies is as important as knowing the actual mean cardiac output value, because the goal is to reestablish end-organ perfusion Thus the parameters monitored now are those assessing end organ blood flow and oxygenation These include on the physical examination level of con-sciousness, urine output, skin mottling, capillary refill, and peripheral skin temperature Metabolic markers such as blood lactate, venous blood oxygen saturation, and arterial

to venous CO2 gradients are useful but do not replace a careful and repeated physical examination Also blood lactate levels are often problematic because failure to clear lactate, if elevated (i.e., >2 mmol/L) may reflect washout

of tissue lactate by the newly increased organ blood flow, impaired liver extraction, or non–perfusion-associated elevations, as seen in severe sepsis If lactate levels do decrease, they will do so over hours and must be monitored over time The optimization phase often requires advanced hemodynamic monitoring to assess the impact of mechanical ventilatory support and vasoactive therapies This phase

of resuscitation should be completed within 4 to 6 hours

of admission, if not sooner

Once blood flow has been established, the care moves into the stabilization period, which can last from several hours to several days depending on the extent of end-organ injury and need for aggressive organ supportive measures, such as mechanical ventilation, hemodialysis, antibiotics, and specific surgeries as indicated This is often the most difficult time in the management of the critically ill Overzealous resuscitation extending beyond optimization phase can lead to massive fluid overload, interstitial edema, intraabdominal hypertension, and impaired oxygenation Regrettably, no clear guidelines exist as to when to stop giving fluid therapy, but at a minimum, fluids should be withheld if the patient is not volume responsive and if they a rent displaying singed of tissue hypoperfusion If patients have signs of tissue hypoperfusion, as listed earlier, and they are also not volume responsive, then the use of cardioactive therapies to augment cardiac function (e.g.,

perfusion metrics (e.g., blood lactate, venous O2 saturation,

venoarterial CO2 gradient), not to some extrinsically defined

value Fourth, ventricular filling pressures, both right and

left atrial pressure, estimated by central venous pressure

and pulmonary artery occlusion pressure, respectively,

do not reflect volume status but can be used to define

contractility and the threat of further fluid resuscitation

to cause compromise Central venous pressure raises are a

stopping rule for fluid infusion because they connote right

ventricular failure and impending acute cor pulmonale

Similarly, pulmonary artery occlusion pressure rises are also

a stopping rule for fluid infusion because they connote left

ventricular failure and impending hydrostatic pulmonary

edema Finally, all responses to stress are by necessity a

coordinated response across all appropriate parts of each

organ system and the body as a whole Thus, although

hypotension may decrease total blood volume, effective

circulating blood volume, cardiac output, and arterial

pres-sure may remain unchanged because of the dynamic effects

on contractility, blood flow distributions, and vasomotor

tone listed above It is the interaction of these different

adaptive mechanisms and not each mechanism alone that

defines the pathologic signatures of disease states

CIRCULATORY SHOCK: RESUSCITATION

GUIDELINES AND PROTOCOLS

Recently, several large prospective clinical trials on the

emergency department treatment of circulatory shock,

usually resulting from sepsis, have not been able to prove

that protocol-based resuscitation is superior to aggressive

resuscitation titrated to individual patient needs.2 Although

these findings should not surprise anyone, they do

under-score the reality that resuscitation must be titrated based

on known physiologic principles and then these physiologic

principles must be applied in a continuous and titrated

manner based on the patient’s specific responses The

principles of critical care management have been presented

as a play in four acts: salvage, optimization, stabilization,

and deescalation.3

The first act is rescue, when the primary goal is merely

to keep the patient alive long enough for other more

defini-tive treatments to start to work while preventing further

tissue ischemic injury, if possible The focus here is on

maintaining an adequate mean arterial pressure primarily

to support cerebral and cardiac blood flows Assuming that

the critically ill patient initially is seen in either circulatory

shock, acute respiratory failure, or a combination of both,

initial resuscitation includes maintenance of a patent airway,

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Chapter 2 / The Pathophysiologic Foundations of Critical Care 9

perfusion pressure and microcirculatory flow, it is not clear that the cells being perfused will respond with increased metabolic activity and recovery, as seen in patients with primarily hypoperfusion-induced organ injury In septic shock patients with evidence of new end organ injury, the goals of resuscitation are less clear and the potential for complications higher than with other forms of circulatory shock At present, the clinical literature supports aggressive initial resuscitation to restore blood pressure, but after that most literature supports remaining in a stabilization period until the signs of infection abate

SUMMARY

This introductory overview emphasized the complex processes, often with autonomic nervous system oversight, that interplay to maintain a relatively stable internal environ-ment and outward signs of health The signs of diminished organ system health reflect initially decreased metabolic reserve and then increased sympathetic tone at rest Once organ failure becomes overtly obvious, the process has become far advanced Potentially, the most effective way

to identify impending organ system failure is to continually assess organ system reserve using functional physiologic monitoring tests However, earlier identification of progres-sive organ injury may allow for earlier treatment of the initiating process, if a known treatment exists

Key Points

1 Cardiovascular resuscitation from circulatory shock requires an understanding of the key processes that define cardiovascular homeostasis.

2 The primary determinant of oxygen delivery to the body that can be easily mediated is cardiac output.

3 Cardiac output is primarily determined by the interaction between the effective circulating blood volume, vasomotor tone, and cardiac performance.

A complete reference list can be found online at Expert

-Consult.com

dobutamine) and support organ perfusion pressure (e.g.,

norepinephrine) is indicated During this time, if antibiotics

are given, their specific dose and nature must be focused

as narrowly as possible to minimize complications and

the emergence of drug resistance Similarly, homeopathic

treatments (e.g., head of the bed elevation, stress ulcer

and venous thrombosis prophylaxis) must be started and

maintained as long as risk is present (e.g., intubated and

mechanical ventilation)

It is not clear when deescalation of therapies should

start However, as a general principle, if a patient does not

need a treatment to sustain normal homeostasis, it should

be removed This is the general principle for weaning from

mechanical ventilation and also should be used for weaning

from vasoactive drug therapies, intravascular fluid infusions,

starting or increasing enteral feeding, and as third space

fluid mobilizes postresuscitation, often diuretics to minimize

edema and aid in diuresis Patients with persistent renal

insufficiency often need dialysis to remove this excess fluid,

even if not otherwise requiring renal replacement therapy

SEPSIS AND SEPTIC SHOCK

The most common process causing organ injury and death

in the critically ill patient is sepsis resulting from infection.4

Often this is an expected end point in the process of dying

and only facilitates the dying process However, sepsis

occurs across all critically ill patients, many of whom would

otherwise survive Unlike other forms of circulatory shock,

sepsis represents a protean systemic inflammatory process

that encompasses altered immune responsiveness,

metabo-lism, endocrine function, and peripheral vascular

autoregula-tion Although aggressive resuscitation and appropriate

antibiotics are highly effective at reversing this process if

started very early, often treatment is delayed This delay

may be due to delayed entry of the patient into the acute

care system because the infectious process initially appeared

benign or because of failure of the acute healthcare system

to identify patients progressing into sepsis from simple

flulike symptoms Still, in the patient presenting with sepsis

associated with hypotension and evidence of new end-organ

injury, it is not clear if aggressive resuscitation alters

outcome This is because cellular injury and adaptation

often develops with sustained systemic inflammation It is

unclear if resuscitation efforts will improve microcirculatory

blood flow Even if fluid and vasopressors restore organ

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Chapter 2 / The Pathophysiologic Foundations of Critical Care 9.e1

References

1 Cecconi M, De Backer D, Antonelli M, et al Consensus on

Circulatory Shock and Hemodynamic Monitoring, Task Force

of the European Society of Intensive Care Medicine Intensive

Care Med 2014;49:1795-1815.

2 Angus DC, Barnato AE, Bell D, et al A systematic review and

meta-analysis of early goal-directed therapy for septic shock:

the ARISE, ProCESS and ProMISe Investigators Intensive Care

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CHAPTER 3

Mechanical Ventilation

David J Dries and John J Marini

This chapter will:

1 Describe the physiologic basis of mechanical ventilatory

support

2 Discuss pressure- and volume-targeted ventilation

3 Review common modes of mechanical ventilation

4 Indicate conceptual changes that shape current approaches

Positive-pressure ventilation first was applied clinically

during the poliomyelitis epidemics of the 1950s.1 Since

that time, mechanical ventilatory support has become

emblematic of critical care medicine Early ventilation used

neuromuscular blocking agents to control respiratory efforts

Today, patient control of ventilation is encouraged after

the initial stabilization phase, and awareness of the

com-plications associated with neuromuscular blockade is

growing.2 Importantly, the increasing recognition that

ventilators can induce various forms of lung injury has led

to reappraisal of the goals of ventilatory support.3 Although

it seems that intricate new modes of mechanical ventilation

have been introduced to clinical practice, the fundamental

principles of ventilatory management of critically ill patients

remain unchanged

Positive-pressure ventilation can be lifesaving in patients

with hypoxemia or respiratory acidosis that is refractory

to simpler measures (Fig 3.1) In patients with severe

cardiopulmonary distress and excessive work of breathing,

mechanical ventilation effectively offloads the burden

otherwise placed on the respiratory muscles.4 In the setting

of respiratory distress, ventilatory activity may account for

as much as 40% of total oxygen consumption.5 Under these

circumstances, relief of the breathing workload by

mechani-cal ventilation allows diversion of oxygenated blood to

other tissue beds that may be vulnerable to ischemia

Reversal of fatigue, which may contribute to respiratory

failure, depends on the respiratory muscle rest that

mechani-cal ventilation affords Positive-pressure ventilation can

reverse or prevent atelectasis through recruitment and

prevention of collapse Although mechanical ventilation

is not therapeutic by itself, improved gas exchange and

relief from excessive respiratory muscle work give the lungs

and airways a chance to heal Conversely, high ventilatory

pressures may aggravate or initiate alveolar damage These

dangers of ventilator-induced lung injury have led to

reap-praisal of the objectives of mechanical ventilation Rather

than seeking normal arterial blood gas values, clinicians should accept a degree of respiratory acidosis (and even relative hypoxemia) to avoid large tidal volumes and high inflation pressures

Mechanical ventilation strategies should be tailored to the underlying pulmonary disease For example, in patients with acute respiratory failure, chronic obstructive pulmonary disease, asthma, or other conditions associated with unusu-ally high minute ventilation requirements, gas trapping develops because patients have inadequate expiratory time available before the next breath begins Patients experiencing this “breath stacking” have residual positive end-expiratory pressure (PEEP) that was not set by the clinician, termed

auto-PEEP Retained peripheral gas makes triggering the

ventilator difficult, because the patient must generate a negative pressure equal in magnitude to the level of auto-PEEP in addition to the trigger threshold of the machine This is one factor that may contribute to a patient’s inability

to trigger the ventilator despite obvious respiratory effort Auto-PEEP may remain undetected (on the pressure tracing) because it is not registered routinely during tidal cycles Persistent end-expiratory flow driven by the excess pressure

Pulmonary vascularresistance increasedVenous return

Ventricularinterdependence

Left ventricleRight ventricle

Juxtacardiacpressureincreased

FIGURE 3.1 Factors responsible for the hemodynamic effects seen with positive-pressure ventilation A drop in intrathoracic pressure compresses the vena cava and thus decreases venous return Alveolar distention compresses the alveolar vessels, and the resulting increases in pulmonary vascular resistance and right ventricular afterload produce a leftward shift in the interventricular septum Left ventricular compliance is reduced by both the bulging septum and the higher juxtacardiac pressure resulting from distended lungs

(Adapted from Tobin MJ Mechanical ventilation N Engl J Med

1994;330:1056–1061.)

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Chapter 3 / Mechanical Ventilation 11prompt aggressive intervention if pH remains acceptable and the patient remains alert, especially if CO2 retention occurs slowly Many patients require ventilatory assistance despite levels of alveolar ventilation that would be appropriate to normal resting metabolism For example, in patients with metabolic acidosis and neuromuscular weakness or airflow obstruction, PaCO2 may drop to 40 mm Hg or less but not suf-ficiently to prevent acidemia The physiologic consequences

of altered pH are still debated and clearly depend on the underlying pathophysiology and comorbidities However,

if not quickly reversible by simpler measures, a sustained

pH greater than 7.65 but less than 7.10 often is considered sufficiently dangerous to require correction by mechanical ventilation Inside these extremes, the threshold for initiating support varies with the clinical setting.8 For example, a lethargic patient with asthma who is struggling to breathe can maintain a normal pH until shortly before suffering a respiratory arrest, whereas in an alert cooperative patient with chronically blunted respiratory drive, pH may fall to 7.25 or lower before the patient recovers uneventfully in response to aggressive bronchodilation, corticosteroids, and oxygen In less obvious situations, the decision to ventilate should be guided by trends in pH, arterial blood gas values, mental status, dyspnea, hemodynamic stability, and response

to therapy The ongoing need for ventilatory assistance must

be assessed repeatedly

Inadequate Oxygenation

Arterial oxygenation results from complex interactions between systemic oxygen demand, cardiovascular adequacy, and the efficiency of pulmonary oxygen exchange Improving cardiovascular performance and minimizing O2 consumption (by reducing fever, agitation, pain, etc.) may improve dramatically the balance between delivery and consumption

of oxygen Transpulmonary oxygen exchange can be aided

by supplementing FiO2, by using PEEP, by changing the pattern of ventilation to increase mean airway pressure (and consequently, mean alveolar pressure and average lung size), or by prone positioning In patients with edematous

or injured lungs, relief of an excessive breathing workload may improve oxygenation by relaxing the expiratory muscles and allowing mixed venous O2 saturation to improve, thereby reducing the venous admixture.10

Modest fractions of inspired oxygen are administered

to nonintubated patients by means of masks or nasal nulas Controlled O2 therapy is best delivered to the nonintubated patient with a well-fitting Venturi mask, which keeps FiO2 nearly constant despite changes in inspiratory flow requirements Without tracheal intubation or a sealed noninvasive ventilation interface, delivery of high FiO2 can

can-be achieved only with a tight-fitting, nonrebreathing mask that is flushed with high flows of pure O2 Unfortunately, apart from the risk of O2 toxicity, such a mask often becomes displaced or must be removed intentionally for eating or expectoration Intubation facilitates the application of PEEP and CPAP needed to avert oxygen toxicity and enables extraction of airway secretions

Excessive Respiratory Workload

A common reason for mechanical assistance is to amplify ventilatory power The respiratory muscles cannot sustain tidal pressures greater than 40% to 50% of their maximal isometric pressure Respiratory pressure requirements rise with minute ventilation and the impedance to breathing

provides the clue Newer machines have software to detect

auto-PEEP under controlled conditions In older machines,

occluding the expiratory port of the circuit at the end of

expiration in a fully relaxed patient causes pressure in the

lungs and ventilator circuit to equilibrate and the level of

auto-PEEP to be displayed on the manometer.6 If auto-PEEP

or breath stacking is detected, improving airflow resistance,

extending the expiratory time, and reducing the minute

ventilation help reverse the process

INDICATIONS FOR MECHANICAL

VENTILATION

Although often made concurrently, the decisions to institute

or withdraw mechanical support should be made

indepen-dently of those to perform tracheal intubation or use positive

end-expiratory pressure This statement is especially true

in light of improved noninvasive (nasal and mask) options

for supporting ventilation with continuous positive airway

pressure (CPAP).7 As the ventilator assumes the work of

breathing, important changes occur in pleural pressure,

ventilation distribution, and cardiac output Mechanical

assistance may be needed because oxygenation cannot be

achieved with an acceptable FiO2 without manipulation of

PEEP, mean airway pressure, and the pattern of ventilation

or because spontaneous ventilation places excessive

demands on ventilatory muscles or on a compromised

cardiovascular system.8 Relief of the work of breathing

simultaneously reduces the associated need for cardiac

output, diminishes oxygen extraction, and improves

oxy-genation efficiency

Inadequate Alveolar Ventilation

When other therapeutic measures are insufficient to avert

apnea and ventilatory deterioration, mechanical

breath-ing assistance clearly is indicated In such cases, there

are usually signs of respiratory distress or advancing

obtundation, and serial blood gas measurements show a

falling blood pH and a stable or rising PaCO2 Although

few clinicians would withhold mechanical assistance in

the patient in whom blood pH trends steadily downward

and there are signs of physiologic intolerance, there is less

agreement about the absolute values of PaCO2 and blood

pH that warrant such intervention; these values clearly vary

with the specific clinical setting and the duration of the

abnormality In fact, after intubation has been accomplished,

pH and PaCO2 values may be deliberately allowed to drift

far outside the normal range to avoid the high ventilating

pressures and tidal volumes that tend to induce lung damage

This strategy—permissive hypercapnia—is now considered

integral to a lung-protective ventilatory approach to the

acute management of severe asthma and adult respiratory

distress syndrome.9 Acute hypercapnia has well-known and

potentially adverse physiologic consequences Nonetheless,

experimental work in varied models of clinical problems—

notably, ischemia-reperfusion and ventilator-induced lung

injury—clearly indicates that certain forms of cellular

injury actually are attenuated by hypercapnia Whether it

is hypercapnia or the associated change in hydrogen ion

concentration that exerts the attenuating effect is still a

subject of investigation

Blood pH is generally a better indicator than PaCO2 of

the need for ventilatory support Hypercapnia should not

Trang 36

tory modes as options for full or partial ventilatory assistance After the breath is initiated, these modes quickly attain a targeted amount of pressure at the airway opening until a specified time (pressure-control) or flow (pressure-support) cycling criterion is met Maximal pressure is controlled, but tidal volume is a complex function of applied pressure and its rate of approach to target pressure, available inspira-tory time, and the impedance to breathing (compliance, inspiratory and expiratory resistance, and auto-PEEP) High-flow capacity, pressure-targeted ventilation compen-sates well for small air leaks and is therefore appropriate for use with leaking or uncuffed endotracheal tubes, as in neonatal or pediatric applications

Because of its virtually “unlimited” ability to deliver flow and its decelerating flow profile, pressure-targeted ventilation also is an appropriate choice for spontaneously breathing patients with high or varying inspiratory flow demands, which usually peak early in the ventilatory cycle The decelerating flow profiles of pressure-targeted modes also improve the distribution of ventilation in lungs with heterogeneous mechanical properties (widely varying time constants) Apart from limiting the lung’s potential exposure

to high airway pressure and the risk of barotrauma, targeted modes of ventilation often prove helpful for the adult patient whose airway cannot be completely sealed (e.g., in bronchopleural fistula)

pressure-Flow-Controlled, Volume-Cycled Ventilation

For many years, flow-controlled, volume-cycled control) ventilation has been the technique of choice for support of seriously ill adult patients Flow can be controlled

(assist-by selecting a waveform (e.g., constant or decelerating) and setting a peak flow value or by selecting a flow waveform and setting the combination of tidal volume and inspiratory time Every breath triggered by patient effort is met with

a cycle that has an identical flow trajectory for a fixed inspiratory period Through control of the tidal volume and backup frequency, a certain lower limit for minute ventilation can be guaranteed, but the pressure required to ventilate varies widely with the impedance to breathing Moreover, once this mode is chosen, the preset flow profile remains inflexible to increased (or decreased) inspiratory flow demands The high-pressure alarm often is triggered

by expiratory efforts that begin during the ventilator’s time-determined inflation phase

Differences Between Pressure-Targeted and Volume-Targeted Ventilation

After the decision has been made to initiate mechanical ventilation, the clinician must decide to use either pressure-controlled or volume-cycled ventilation For a well-monitored, passively ventilated patient, pressure-targeted and volume-targeted modes can be used with virtually identical effects With either method, FiO2, PEEP, and backup frequency must be selected If pressure control (sometimes referred to as pressure assist-control) is used, the targeted inspiratory pressure (above PEEP) and the inspiratory time (T1) must be selected (usually with consideration of the desired tidal volume) Although the exhalation valve remains closed, flow may cease when thoracic recoil pressure equals the pressure target An “inspiratory hold” will then occur for the remainder of the set T1 Pressure support differs from pressure control, in that each pressure-supported breath must be initiated (“triggered”) by the patient Furthermore,

Patients with hypermetabolism or metabolic acidosis often

need ventilatory support to avoid decompensation

Impair-ment of ventilatory drive or muscle strength diminishes

ventilatory capacity and reserve

Although little effort is expended by normal subjects

who breathe quietly, the O2 demands of the respiratory

system account for a very high percentage of total body

oxygen consumption (V̇o2) during periods of physiologic

stress.5,10 Experimental animals in circulatory shock that

receive mechanical ventilation survive longer than their

unassisted counterparts Moreover, in patients with

com-bined cardiorespiratory disease, attempts to withdraw

ventilatory support for cardiac rather than respiratory reasons

often fail Such observations demonstrate the importance

of minimizing the ventilatory O2 requirement during cardiac

insufficiency or ischemia to rebalance myocardial O2 supply

with requirements and/or allow diaphragmatic blood flow

to be redirected to other oxygen-deprived vital organs

Moreover, reducing ventilatory effort may improve afterload

to the left ventricle Although it is possible to use

nonin-vasive ventilation or CPAP alone in patients affected by

cardiac insufficiency, fatigue often sets in unless underlying

oxygen requirements are reduced substantially; such

reduc-tion in oxygen demand often requires adequate sedareduc-tion

or higher pressures than can be provided noninvasively

Over time, inhibition of cough by the pressurized mask as

well as mouth-breathing of large volumes of poorly

humidi-fied gas may result in retention of secretions

TYPES OF INVASIVE VENTILATION

To accomplish ventilation, a pressure difference must be

developed phasically across the lung This difference can

be generated by negative pressure in the pleural space

developed by respiratory muscles, by positive pressure

applied to the airway opening, or by a combination of the

two Although of major historical interest, negative-pressure

ventilators are seldom appropriate for the modern acute

care setting and are not discussed further For machine-aided

cycles, the clinician must determine the machine’s minimum

cycling rate, the duration of its inspiratory cycle, the baseline

pressure (PEEP), and either the pressure to be applied or

the tidal volume to be administered, depending on the

mode selected.4

Positive-pressure inflation can be achieved with machines

that control either of the two determinants of ventilating

power—pressure or flow—and that terminate inspiration

according to pressure, flow, volume, or time limits.4,11–13

The waveforms of both flow and pressure cannot be

con-trolled simultaneously, however, because pressure is

developed as a function of flow and the impedance to

breathing, which is unalterably determined by the

uncon-trolled parameters of resistance and compliance Thus the

clinician has the choice of controlling pressure, with tidal

volume as a resulting (dependent) variable, or of controlling

flow, with pressure as the dependent variable Although

older ventilators offered only a single control variable and

single cycling criterion, positive-pressure ventilators of the

latest generation enable the clinician to select freely among

multiple options

Pressure-Preset (Pressure-Targeted) Ventilation

Modern ventilators provide preset or

pressure-targeted (e.g., pressure-control or pressure-support)

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ventila-Chapter 3 / Mechanical Ventilation 13

or pressure-targeted breaths.4 When pressure is the targeted variable and inspiratory time is preset, the mode is known

as pressure-control or, less commonly, pressure assist-control ventilation Sensitivity to inspiratory effort can be adjusted

to require a small or large negative pressure deflection below the set level of end-expiratory pressure to initiate mechanical inspiration Most of the newest machines can be flow-triggered, initiating a cycle when a flow deficit is sensed

in the expiratory limb of the circuit relative to the inspiratory limb during exhalation As a safety mechanism, a backup rate

is set so that if the patient does not initiate a breath within the number of seconds dictated by that backup frequency target, the machine cycle begins automatically A backup rate set high enough to cause alkalosis blunts respiratory drive and terminates the patient’s efforts to breathe at the apneic threshold for PCO2 In awake, normal subjects, this threshold usually is achieved when the PaCO2 is lowered abruptly to 28 to 32 mm Hg; it may be considerably higher during sleep Changes in machine frequency have no effect

on minute ventilation unless the backup frequency is set sufficiently high to terminate patient respiratory efforts Thus assist-control ventilation is not appropriate for use

in weaning

Synchronized Intermittent Mandatory Ventilation

In a passive patient, synchronized intermittent mandatory ventilation (SIMV) cannot be distinguished from assist-control ventilation; ventilation then is determined by the mandatory frequency and tidal volume.15 If the patient initi-ates effort within the mandated interval, a different type of breath, usually pressure-supported, is allowed Thus, when

a breath is initiated outside the mandated synchronization

“window,” tidal volume, flow, and inspiratory-to-expiratory time ratio are determined by patient effort, any pressure support, and respiratory system mechanics, not by ventilator settings.16 These spontaneous breaths tend to be of small volume and are highly variable from breath to breath Respi-ratory work associated with these breaths may be significant, particularly for the patient with underlying cardiopulmonary disease The SIMV mode, although much less popular than

in previous years, currently is used occasionally to gradually augment the patient’s work of breathing by lowering the mandatory breath frequency or to ensure backup breaths

the off-cycling criterion for pressure support is flow rather

than time, so cycle length is free to vary with patient effort

If volume-cycled ventilation is used, the clinician may select

(depending on ventilator) either tidal volume and flow

delivery pattern (waveform and peak flow) or flow delivery

pattern and minimum minute ventilation (with tidal volume

the resulting quotient of expiratory volume [VE] and backup

frequency) (Table 3.1)

The fundamental difference between pressure-targeted

and volume-targeted ventilation is implicit in their names;

pressure-targeted modes guarantee pressure at the expense

of letting tidal volume vary, and volume-targeted modes

guarantee flow—and, consequently, the volume provided

to the closed circuit in the allowed inspiratory time (tidal

volume)—at the expense of letting airway pressure vary

This distinction governs how the two modes are used in

clinical practice

MODES AND SETTINGS

Technologic developments have provided a wide variety

of modes by which a patient may be mechanically

venti-lated.14 Various modes have been developed with the hope

of improving gas exchange, patient comfort, or rapid return

to spontaneous ventilation Almost any of these newer

modes, however, can be adjusted to allow full rest of the

patient or periods of exercise Thus, in the great majority

of patients, choice of mode is merely a matter of clinician

or patient preference Because controlled ventilation with

abolition of spontaneous breathing rapidly leads to

decon-ditioning or gradual atrophy of respiratory muscles, various

assisted modes that are triggered by inspiratory efforts are

preferred.2 The most common triggered modes are

assist-control ventilation, intermittent mandatory ventilation, and

pressure-support ventilation Because of their importance

and ubiquity, these modes are detailed here

Assist-Control Ventilation

In assist-control ventilation (or assisted mechanical

ventila-tion [AMV]), each inspiraventila-tion triggered by the patient is

powered by the ventilator by means of either volume-cycled

TABLE 3.1

Comparison of Pressure-Control and Volume-Control Breaths: Fundamental Dichotomy Between Pressure and

Volume Strategies in Mechanical Ventilatory Support, Showing Dependent and Independent Variables With Points for Clinician Input

Tidal volume Set by clinician

Peak inspiratory

pressure Variable with changes in patient effort and respiratory system impedance Set by clinicianRemains constant

Inspiratory time Set directly or as a function of respiratory frequency

and inspiratory flow settings Set by clinicianRemains constantInspiratory flow Set directly or as a function of respiratory frequency

and inspiratory flow settings Variable with changes in patient effort and respiratory system impedanceInspiratory flow

waveform Set by clinicianRemains constant

Can use constant, sine, or decelerating flow waveform

Variable with changes in patient effort and respiratory system impedance

Flow waveform always is decelerating

Modified from Branson RD, Campbell RS Modes of ventilator operation In MacIntyre NR, Branson RD, eds Mechanical ventilation Philadelphia, WB

Saunders, 2001, p 55.

Trang 38

sudden decompensation.8 New options for patient-controlled breathing that offer advantages over PSV are being employed more frequently (see later in this chapter)

Routine Settings

Ventilator settings are based on the patient’s size and tion The risk of toxic oxygen effects is minimized by using the lowest fraction of inspired oxygen that can satisfactorily oxygenate arterial blood The usual goal is an arterial oxygen tension (PaO2) of 60 mm Hg or an oxygen saturation of 90%, because higher values do not substantially enhance tissue oxygenation and because slight reductions in PaO2

condi-cause oxygen saturation and content to fall precipitously below that value.4

Historically practice involved setting tidal volumes at

10 to 15 mL per kg body weight, which is two to three times normal.4 This approach currently is considered inap-propriate in light of convincing data from experiments indicating that alveolar overdistention can produce endo-thelial, epithelial, and basement membrane injuries associ-ated with increased microvascular permeability and lung injury (ventilator-induced lung injury).3 To reduce this risk, monitoring alveolar volume would be ideal, but this is not feasible A reasonable substitute is to monitor peak alveolar pressure, as obtained from the plateau pressure measured

in a relaxed patient by briefly occluding the ventilatory circuit at end-inspiration The incidence of ventilator-induced lung injury rises markedly when plateau pressure

is elevated and the excursion of alveolar pressure needed

to deliver each tidal volume (plateau minus PEEP, or “driving pressure”) is high In patients with severe underlying pulmonary dysfunction, there is a growing tendency to limit the tidal volume delivered to less than 7 mL/kg to achieve a plateau (alveolar) pressure no higher than 30 cm

H2O Because it is transpulmonary pressure that distends the lung, in patients with very noncompliant chest walls, this upper limit value in plateau pressure may be relaxed somewhat Conversely, if the patient makes spontaneous efforts to breathe, airway pressures lower than that 30 cm

HO guideline may not be lung protective Adherence to the low driving pressure approach may lead to an increase

in PaCO2 Acceptance of elevated carbon dioxide tension

in exchange for controlled alveolar pressure, as previously

discussed, is termed permissive hypercapnia It is important

to focus on pH rather than arterial PCO2 if this approach

is employed In a patient in whom the pH falls below 7.20, some clinicians would increase minute ventilation or administer bicarbonate

Flow-Targeted, Volume-Controlled Ventilation

The rate of ventilation that is set depends on the mode and

on patient requirements With assist-control ventilation, a backup rate should be about 4 breaths/min less than the patient’s spontaneous rate; this setting ensures that the ventilator will continue to supply adequate minute ventila-tion if there is a sudden decrease in output from the patient’s respiratory centers With SIMV, the rate is typically high

at first and then gradually decreased in accordance with patient tolerance

A peak flow rate of about three times the minute tion commonly is selected for the constant inspiratory flow profile, or about four to six times minute ventilation if the profile is decelerating Peak inspiratory flow rate should

ventila-be fast enough to satisfy peak flow demand but not so high

without excessive asynchrony when the patient’s breathing

pattern is unstable (e.g., Cheyne-Stokes) The mandated

breaths may be pressure or flow targeted and often are

selected to be somewhat larger than the patient’s own

pressure-supported breaths

Pressure-Support Ventilation

Pressure-support ventilation (PSV) is a method in which each

breath taken by a spontaneously breathing patient receives a

pressure boost The patient must trigger the ventilator to

acti-vate this mode; thus PSV is not applied in passive, paralyzed,

or sedated patients Ventilation is determined by preset

inspiratory pressure, patient-determined rate, and patient

effort Once a breath is triggered, the ventilator attempts to

maintain inspiratory pressure at the clinician-determined

level using whatever flow is necessary to accomplish this

goal.17,18 As tidal volume rises, eventually flow begins to fall

as a result of either cessation of patient inspiratory effort

or increasing elastic recoil of the respiratory system The

ventilator maintains inspiratory pressure until inspiratory

flow falls by an arbitrary amount (for example, to 25% of

initial flow) or below an absolute flow rate Apart from

the selected level of pressure support, the clinician can

vary the rate of rise to the targeted pressure and, perhaps

more importantly, the flow off-switch The patient’s work

of breathing can be increased by lowering the inspiratory

pressure or making the trigger less sensitive The work of

breathing can increase inadvertently if respiratory system

mechanics change with no change in ventilator settings A

potential advantage of PSV is greater patient comfort and,

for some patients with very high respiratory drive, reduced

work of breathing compared with volume-preset modes

PSV hybridizes the power of the machine and the patient,

providing assistance that ranges from no support at all to

fully powered ventilation depending on the machine’s

developed pressure relative to patient effort.19 Because the

depth, length, and flow profile of the breath are influenced

by the patient, well-adjusted PSV tends to be relatively

comfortable in comparison with time-cycled modes

Adapt-ability to the vagaries of patient cycle length and effort can

prove especially helpful for patients with erratic breathing

patterns that otherwise would be difficult to adapt to a

fixed flow profile or set inspiratory time (e.g., because of

chronic obstructive pulmonary disease, anxiety, or

Cheyne-Stokes breathing) Because the cycle length is flow-adjustable

by the patient, it is not uncommon for high-level PSV to

be the only commonly available mode that can be tolerated

during severe dyspnea The transition to spontaneous

breathing is eased by the gradual removal of machine

support Although PSV has widespread application as a

weaning mode, it also is valuable in offsetting the resistive

work required to breathe spontaneously through an

endo-tracheal tube, such as during CPAP or SIMV When used

to support ventilation, the pressure support level should

be adjusted to maintain adequate tidal volume at an

accept-able frequency (<30 breaths/min) In theory, PSV would

provide sufficient power for the entire work of breathing

if it were set to meet or exceed the average inspiratory

pressure required per breath (Preq) For a normal subject

breathing at a moderate rate, Preq is amazingly small, seldom

exceeding 7 cm H2O For patients who are candidates for

weaning from ventilation, VE usually approximates 10 L/

min or less, and Preq commonly does not exceed 10 to 15 cm

H2O This explains why patients seem to be “weaning

smoothly” until some rather low threshold value of PSV

is reached, at which point further reductions precipitate

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Chapter 3 / Mechanical Ventilation 15

patient’s own ventilatory rhythm cycles into its exhalation phase Delayed opening of the exhalation valve causes the patient to “fight the ventilator.” As a very general rule of

thumb, the ventilator’s average inspiratory flow should

approximate four times the minute ventilation, as already noted Peak flow should be set 20% to 30% higher than this average value when the decelerating waveform is used Peak airway pressure is influenced by inspiratory flow rate, airway resistance, tidal volume, and total thoracic compli-ance During an end-inspiratory pause, the plateau airway pressure reflects the maximum stretching force applied to

a typical alveolus and its surrounding chest wall To avoid barotrauma, maximum pressure (alarm pressure) should

be set at no more than 15 to 20 cm H2O above the peak pressure observed during a typical breath during constant flow The pop-off alarm should be set closer than this (within

10 cm H2O) if a decelerating flow waveform or pressure control is used, because under those conditions, end-inspiratory dynamic and static (plateau) pressures are not

as widely separated (Table 3.2)

GENERAL PRINCIPLES OF PATIENT MANAGEMENT

Key observations made over the past decade emphasize the importance of avoiding invasive ventilation whenever possible When required, limiting the duration of its applica-tion helps to protect the viability of the lung, diaphragm, and skeletal musculature while hastening the return to pre-illness status Recent conceptual advances in several areas already influence practice significantly, and more extensive deployment of improved technologies offer welcome options for our most difficult patients

as to produce discomfort or excessive shearing stress An

inspiratory flow rate of 40 to 60 L/min is appropriate if the

minute ventilation is 12 L/min and the profile is square

(50–70 L/min if the profile is decelerating).20 In certain

patients with obstructive pulmonary disease, better gas

exchange may be achieved by higher flow rates, probably

because the resulting increase in expiratory time allows

for more complete emptying of regions of gas trapping

Patients with severe airflow obstruction may prefer a

constant flow profile If the flow rate is insufficient to meet

the patient’s ventilatory requirements, the patient will strain

against his or her own pulmonary impedance and that of

the ventilator, with a consequent increase in the work of

breathing.21 Examination of the monitoring waveform for

airway pressure may be helpful when flow rate and ventilator

trigger sensitivity are adjusted

Few aspects of ventilator management are more

contro-versial than the use of PEEP In patients with acute

respira-tory distress syndrome (ARDS), a higher PEEP substantially

improves oxygenation The reason is probably a reduction

in intrapulmonary shunting as a result of recruitment

(prevention of collapse) and redistribution of lung water

from alveoli to the perivascular interstitial space.22 PEEP

does not decrease total extravascular lung water Provided

that the improvement in PaO2 is not offset by decline in

cardiac output, FiO2 can be decreased The addition of

PEEP influences lung mechanics Patients with acute lung

injury commonly have reduced end-expiratory lung volume,

so their tidal breathing occurs on the low, flat portion of

the pressure-volume curve By shifting tidal breathing to

a more compliant portion of the curve, PEEP can reduce

the work of breathing.23 In patients with airflow limitation,

auto-PEEP, and difficulty triggering the ventilator, the

addi-tion of external PEEP (to a level not exceeding the level of

auto-PEEP) can help counteract dynamic hyperinflation,

because under these specific circumstances, the patient

needs only to decrease alveolar pressure to 1 to 2 cm H2O

below the level of external PEEP, rather than below zero.24

An appropriate PEEP setting applied to bedridden adults

without significant coexisting pulmonary problems is 3 to

7 cm H2O, but this value can range to 15 to 20 cm H2O or

higher in the setting of ARDS or acute lung injury

Other Settings

Flow-controlled, volume-cycled ventilators allow the

clini-cian to choose the inspiratory flow rate and define its contour

(constant “square” or decelerating).25 Inappropriately rapid

inspiratory flow rates may worsen the distribution of

ventila-tion in some patients; however, a decelerating flow waveform

helps satisfy rapid early inspiratory flow demand Although

peak pressure rises as flow rate increases, the mean airway

pressure averaged over the entire ventilatory cycle may

remain unchanged or may even fall as flow rate increases

Longer exhalation time is a marked advantage for some

patients with airflow obstructions The extent to which the

ventilator takes up the inspiratory work of breathing is a

function of the margin by which flow delivery exceeds

flow demand It is mandatory that the flow metered by the

ventilator meets or exceeds the patient’s flow demand

throughout inspiration Otherwise, the ventilator not only

fails to reduce the work of breathing but also may force

the patient to pull against the resistance of the ventilator

circuitry as well as against his or her own internal impedance

to airflow and chest expansion.26

Comfortably rapid inspiratory flow rates also are desirable

to ensure that the machine completes inflation before the

Trigger Limit Cycle Baseline Conditional variablesControl subsystems: Control circuit Drive mechanism Output control valve Modes of ventilation

Pressure Volume Flow Displays

Control circuit alarmsOutput alarms

Modified from Chatburn RL, Branson RD Classification of mechanical

ventilators In MacIntyre NR, Branson RD, eds Mechanical ventilation

Philadelphia: WB Saunders; 2001: p3.

Trang 40

heterogeneity, improved recruitment of unstable lung units, and better airway secretion drainage.32 Some investigators have reported reductions in ventilator-associated pneumonia incidence, as well Although prone positioning must be conducted by an experienced nursing team, it recently has regained popularity and generally is considered to be a lifesaving standard of practice for appropriately selected patients

Timely Use of Muscle Relaxants

Until relatively recently, neuromuscular blocking agents had been used less often because of concern for lingering weakness after their use However, during the initial phase

of ventilatory support, patients may breathe so vigorously

as to make coordination with a mechanical ventilator ficult and to apply a dangerous tidal stresses to lung tissue Moreover, expiratory muscle activity may compress the chest wall, preventing PEEP from its intended recruiting action and thereby impairing oxygenation However, a landmark French study demonstrated that when neuro-muscular blocking agents are applied early on in the course

dif-of ARDS for less than 48 hours, patients with paralysis may improve mortality risk without detectable consequences for neuromuscular functioning.33 The precise reason for that benefit is unclear, particularly because the mortality advantage emerged only after several weeks of ICU manage-ment The intriguing results of this well-conducted study lack confirmation at the present time, but use of deep sedation and neuromuscular blocking agents is justified and has taken hold for the initial management of vigorously breathing and agitated patients with life-threatening illness

Ventilator-Induced Diaphragmatic Dysfunction

The diaphragm contracts phasically more than 10 times per minute throughout normal life Perhaps in part for this reason, it appears to be exceptionally susceptible to rapid weakening once its burden has been relieved by high-level ventilatory support The process of diaphragm thinning (demonstrable by ultrasonography and presumably reflecting atrophy) may begin within the first day of its complete rest and progress rapidly thereafter Experiments in animals and observations in patients suggest that ventilator-induced diaphragmatic dysfunction (VIDD) may persist long after normal loading conditions are reapplied.34 Although less well documented, it appears that excessive diaphragmatic loads and dyscoordination with the ventilator cycle may also be damaging

Importance and New Approaches to Patient-Ventilator Synchrony

Differences in timing patterns of the patient’s own neural drive to breathe and the ventilator’s response may be clas-sified as those that involve triggering, power assistance (flow and pressure profiles), and the off switch for exhalation

to begin It has long been understood that dyssynchrony can result in ineffective ventilation, discomfort, and the need for deeper sedation However, recent observations suggest that its consequences include longer duration of machine support, respiratory muscle dysfunction, and other adverse outcomes.35 Although it is not yet clear that the association is causative, it is encouraging that considerable progress has been made in developing modes of support that synchronize closely with the neural drive and timing

Conceptual Advances

Driving Pressure

The difference between plateau pressure and PEEP during

tidal inflation is known as the driving pressure A

sophis-ticated statistical analysis of data from important high-quality

clinical trials indicated that this difference of two static

pressures is more predictive of mortality risk than is either

of its component variables, each of which has been

incrimi-nated as causative for ventilator-induced lung injury (VILI).27

Not only does the maximum tidal inflation pressure exert

an influence on outcome but also the excursion of pressure

appears to be key Although both are undeniably important,

the dynamic strain rather than the static strain appears best

correlated with iatrogenic outcomes The reason for this

relationship is speculative; however, the energy load (power)

applied by the ventilator to the respiratory system during

ventilation is largely dictated jointly by minute ventilation

and driving pressure.28,29 Driving pressure (which may be

computed as the ratio of tidal volume to respiratory system

compliance or as the difference between plateau pressure

and PEEP) may be misleading when the chest wall is

unusually stiff or when spontaneous breathing or auto PEEP

alter its numeric value It remains to be determined

pro-spectively whether restricting driving pressure will prove

efficacious in preventing VILI At present, based on available

data, it appears prudent to limit driving pressure in passively

inflated individuals to 15 cm of water or less.27

Dynamic Determinants of Risk of Ventilator-Induced

Lung Injury

From the time the mechanical ventilation first was associated

with lung injury, clinicians have concentrated on regulating

selected static features of the tidal cycle These include

PEEP, tidal volume, plateau pressure, and the difference

between the latter two variables the driving pressure

However, increasing evidence indicates that it is not only

the range of excursion between PEEP and plateau that

matters but also the rate at which plateau is achieved and

the frequency with which driving pressure excursions are

repeated Thus it is not simply static stress or strain

them-selves that deserve attention, but minute ventilation as well

Other dynamic determinants, such as inspiratory flow rate

and flow profile, appear to modulate their impact.30 Although

it is premature to incriminate the power (inflation energy

per minute) delivered by the ventilator as the key integrating

measure of VILI risk, this would appear to be a promising

area of investigation that could have important bedside

implications for devising a safe ventilation strategy for our

sickest patients

Prone Positioning

There is little evolutionary precedent for sustaining the

supine position for the extended periods we customarily

use in intensive care practice Although sporadic reports of

benefit from prone positioning have appeared since the

mid-1970s, subsequent randomized trials comparing supine and

prone positioning did not convincingly favor the latter until

comparatively recently A well conducted and convincing

trial in which appropriately selected, seriously ill patients

with ARDS were treated early in their courses for extended

periods in the prone position demonstrated a marked

advantage regarding the mortality outcome (PROSEVA).31

Mechanisms for its action include reduction of mechanical

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