Essentials of Evidence-Based Practice of Neuroanesthesia and Neurocritical Care

The current practice of medicine is largely moving toward applying an evidence-based approach. Evidence-based medicine is the integration of best research evidence using systematic reviews of the medical literature and then translating it into practice by selecting treatment options for specific cases based on the best research. Clinicians rely on the availability of evidence and accordingly take decisions to provide best treatment to their patients. Clinical management of neurologically compromised patients is challenging and varied; for this reason, treating physicians including neuroanesthesiologists are always in search of best available evidence for patient management and care. Essentials of Evidence-Based Practice of Neuroanesthesia and Neurocritical Care highlights the various controversies that exist in the practice of neuroanesthesia and provides conclusive evidence-based solutions. This comprehensive resource succinctly discusses evidence-based practice of neuroanesthesia based on systematic reviews in clinical neuroscience research. Topics include neurophysiology: ICP or CPP thresholds; neuropharmacology: intravenous or inhalational anesthetics; and neuromonitoring: ICP monitoring. Evidence-based practice is now an integral part of neuroscience, and this book will help residents and trainees gain knowledge to apply it to their practice.

Endorsements/Reviews:

"Evidence based practice is facilitating changes at a rapid pace in neuroanesthesia and neurocritical care practice. Its practice is exceedingly crucial in neuroanesthesia and neurocritical care considering the criticality of the neurologically sick patients, which leaves little or no room for error for an acceptable outcome in them. Patient management in Neuroanesthesia and neurocritical care has many contentious issues because of rapidly evolving changes in their management which require treatment guided by the latest available evidence in literature. Dr. Hemanshu Prabhakar is a strong proponent of evidence based practice for the management of neurologically ill patients both for surgical procedures and their management in neurointensive care unit. Undoubtedly, this book will be of enormous benefits to the students as well as teachers of neuroanesthesia and neurocritical care sub-specialties." -- Parmod Bithal, Editor-In-Chief, Journal of Neuroanaesthesiology and Critical Care (JNACC)

• Highlights the various controversies that exist in the practice of neuroanesthesia and provides conclusive evidence-based solutions
• Topics include neurophysiology: ICP or CPP thresholds; neuropharmacology: intravenous or inhalational anesthetics; and neuromonitoring: ICP monitoring
• Provides residents and trainees with the knowledge to apply evidence-based practice of neuroanesthesia to their practice

• Language: English
• Publisher: Academic Press
• Release date: Nov 18, 2021
• ISBN: 9780128218280

Book preview

9780128218280_FC

Essentials of Evidence-Based Practice of Neuroanesthesia and Neurocritical Care

First Edition

Hemanshu Prabhakar

Professor, Department of Neuroanaesthesiology and Critical Care, All India Institute of Medical Sciences (AIIMS), New Delhi, India

Table of Contents

Cover image

Title page

Copyright

Dedication

Contributors

Acknowledgments

Section A: Introduction

Chapter 1: Introduction to evidence-based practice

Abstract

Introduction

Evidence-based practice in neuroanesthesia

References

Section B: Neurophysiology

Chapter 2: ICP or CPP thresholds

Abstract

Introduction

Question

Controversy

Evidence

Consensus

Conclusion

References

Chapter 3: Role of hypothermia

Abstract

Introduction

What disease states should target temperature management be considered?

Is one method of cooling superior?

What is the optimal target temperature?

Does time to TTM implementation change outcomes?

What is the optimal duration of TTM to improve outcomes?

What is the optimal rate of rewarming to improve patient outcomes and prevent complications?

Is there an optimal method/protocol to detect and treat shivering?

What are the important complications to evaluate during TTM?

Consensus statement

Conclusion

References

Chapter 4: Mechanical ventilation—PEEP

Abstract

Introduction

The questions/controversy: The brain-lung crosstalk

Laboratory evidence

Clinical evidence

Consensus statement

Conclusions

References

Section C: Neuropharmacology

Chapter 5: Intravenous or inhalational anesthetics?

Abstract

Introduction

Controversies

Consensus statement

Conclusion

References

Chapter 6: Hyperosmolar therapy

Abstract

Introduction

Effect of intravenous hyperosmolar fluids on the brain

Background, mechanism, dosing, clinical use, and adverse effects of common hyperosmotic fluids

The question/controversy

Clinical and practical considerations

Consensus statement

Review of recent literature

Conclusion

References

Chapter 7: Role of nitrous oxide

Abstract

Introduction

The question: Is it safe to use N2O in neurosurgical cases?

The question: Is it safe to use N2O in spine surgeries?

The question: Is N2O safe to be used in interventional neuroradiology?

The question: What is the current status of the use of N2O in pediatric patients undergoing neurosurgical procedures under general anesthesia?

The question: Is it safe to use N2O in the geriatric patient population who are scheduled for neurosurgical procedures under general anesthesia?

Conclusion

References

Chapter 8: Antimicrobial prophylaxis

Abstract

Introduction/background

Clinical evidence

Pharmacotherapy

Conclusion/consensus statement

References

Chapter 9: Role of antiepileptics

Abstract

Introduction

Questions and controversies

Laboratory evidence

Clinical evidence

Consensus statements

Conclusion

References

Chapter 10: Treatment of hypertension

Abstract

Introduction

Definition and classification

Secondary hypertension

Hypertension and cerebral autoregulation

Clinical evidence

Intracerebral hemorrhage

Acute ischemic stroke

Subarachnoid hemorrhage (SAH)

Postoperative hypertension

Conclusion

References

Chapter 11: Role of statins for neuroprotection

Abstract

Introduction

Traumatic brain injury

Acute ischemic stroke

Intracerebral hemorrhage

Aneurysmal subarachnoid hemorrhage

Summary of on-going trials

Conclusion

References

Chapter 12: Role of stem cell therapy in neurosciences

Abstract

Introduction

Properties, sources, and characterization of stem cells

Immunomodulation by stem cells

Neurogenic signaling of stem cells

Role in neurological disorders

Conclusion

References

Section D: Neuromonitoring

Chapter 13: ICP monitoring

Abstract

Introduction

Question: What are the indications for ICP monitoring? (Table 13.1)

Question: What is the ICP threshold for treatment?

Question: How should raised intracranial pressure be managed?

Question: Does ICP monitoring improve outcomes?

Question: What is the optimal cerebral perfusion pressure target?

Conclusion

References

Chapter 14: Type of ICP monitor

Abstract

Introduction

The controversy

Laboratory and clinical evidence

Consensus statement

Type of invasive ICP monitoring

Non-invasive ICP monitoring

Conclusion

References

Chapter 15: Newer brain monitoring techniques

Abstract

Introduction

Why do we need new neuromonitoring technologies?

Novel neuromonitoring technologies

Multimodal neuromonitoring and future directions

Conclusion

References

Chapter 16: Intraoperative neuromonitoring

Abstract

Introduction

Somatosensory evoked potential

Motor evoked potentials

Evoked potential assessment

Electromyography

The question/controversy

Laboratory evidence

Clinical evidence

Spine deformity correction

Intramedullary spinal cord tumor resection

EMG/pedicle screw placement

Cervical spine surgery

Minimally invasive surgery

Tethered cord surgery

Non-surgical applications

Cost-effectiveness

Consensus statement

Conclusion

References

Section E: Neuromonitoring

Chapter 17: Blood transfusion triggers

Abstract

Key points

Introduction

Red blood cells transfusion. Optimal transfusion trigger

Transfusion and coagulation factors. Optimal transfusion trigger

Platelet transfusion. Optimal transfusion trigger

Conclusion

References

Chapter 18: Reversal of anticoagulation in neurosurgical and neurocritical care settings

Abstract

Introduction

Questions/controversy

Laboratory tests for the measurement of anticoagulation activity

Evidence-based recommendations

Conclusion

References

Chapter 19: Role of decompressive craniectomy

Abstract

Introduction

Controversy

Laboratory evidence

Clinical evidence

Consensus statement

Conclusion

References

Chapter 20: Strategies for brain protection

Abstract

Introduction

Question/controversy

Laboratory evidence

Clinical evidence

Consensus statement

Conclusion

References

Further reading

Chapter 21: Anesthesia for carotid endarterectomy

Abstract

Introduction

Anesthetic considerations during carotid endarterectomy

The controversy

Clinical evidence

Evidence-based literature on anesthesia for carotid endarterectomy

Conclusion

References

Further reading

Chapter 22: Anesthesia for acute stroke

Abstract

Introduction

The controversy

Preclinical evidence

Clinical evidence

Conclusion

References

Chapter 23: Anesthesia for spine surgery

Abstract

Overview

Questions/controversies

Evidence-based anesthetic approach for spine surgeries

Conclusions

References

Section F: Neurointensive care

Chapter 24: Choice of sedation in neurointensive care

Abstract

Introduction

The question/controversy

Laboratory evidence

Clinical evidence

Consensus statement and conclusions

References

Chapter 25: DVT prophylaxis

Abstract

Introduction/background

Controversy

Specific disease conditions

Conclusion

References

Chapter 26: Role of steroids

Abstract

Introduction

Controversy

Laboratory evidence

Clinical evidence

Traumatic brain injury (TBI)

Chronic subdural hematoma (CSDH)

Central nervous system infections

Intracerebral hemorrhage (ICH)

Consensus statement

Conclusions

References

Chapter 27: Initiation of nutrition

Abstract

Introduction

The question/controversy

Laboratory evidence

Clinical evidence

Consensus statement

Special consideration in neurological patients

Conclusion

References

Chapter 28: Glycemic control

Abstract

Introduction

Pathophysiology

Controversy

Clinical evidence

Consensus statement

Conclusion

References

Chapter 29: Anesthetics for status epilepticus

Abstract

Introduction

The question/controversy

Clinical evidence

Consensus statement

Conclusions

References

Section G: Ethical issues

Chapter 30: Diagnosing brain death

Abstract

Introduction

The controversy

Clinical evidence for diagnosing death by neurologic criteria

Consensus statement

Conclusion with clinical scenarios

References

Section H: Recent advances

Chapter 31: Simulations in clinical neurosciences

Abstract

Introduction

The question/controversy

Evidence from simulation education research

Evidence from clinical sciences

Consensus statement

Conclusion

References

Section I: Webliography

Chapter 32: Webliography

Index

Copyright

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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.

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ISBN 978-0-12-821776-4

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Dedication

To my parents, my family, and my patients.

To Professor Prathap Tharyan, who taught me the basics of evidence-based practice.

Contributors

Numbers in parenthesis indicate the pages on which the authors’ contributions begin.

Pasquale Anania     Department of Neurosurgery, San Martino Policlinico Hospital, IRCCS for Oncology and Neurosciences, Genoa, Italy

Christopher R. Barnes      Department of Anesthesiology and Pain Medicine, University of Washington, Harborview Medical Center, Seattle, WA, United States

Megan Barra      Department of Pharmacy, Massachusetts General Hospital, Boston, MA, United States

Denise Battaglini

Anesthesia and Intensive Care, San Martino Policlinico Hospital, IRCCS for Oncology and Neurosciences, Genoa, Italy

Department of Medicine, University of Barcelona, Barcelona, Spain

Raphael A.O. Bertasi      Department of Anesthesiology and Perioperative Medicine, Mayo Clinic-Florida, Jacksonville, FL, United States

Tais G.O. Bertasi      Department of Anesthesiology and Perioperative Medicine, Mayo Clinic-Florida, Jacksonville, FL, United States

Sarang Biel     Anesthesiology & Perioperative Medicine, Oregon Health & Science University, Portland, OR, United States

Federico Bilotta     Department of Anesthesiology, Critical Care and Pain Medicine, Sapienza University of Rome, Rome, Italy

Navindra R. Bista      Department of Anaesthesiology, Tribhuvan University Teaching Hospital, Institute of Medicine, Tribhuvan University, Kathmandu, Nepal

Vincent Bonhomme

University Department of Anesthesia and Intensive Care Medicine, Centre Hospitalier Regional de la Citadelle

Department of Anesthesia and Intensive Care Medicine, University Hospital of Liege

Anesthesia and Intensive Care Laboratory, GIGA-Consciousness Thematic Unit, GIGA-Research, Liege University, Liege, Belgium

Gretchen Brophy      Department of Pharmacotherapy and Outcomes Science, Virginia Commonwealth University, Richmond, VA, United States

Vinay Byrappa      Anesthesiology Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates

Maria J. Colomina

Department of Anaesthesiology, Critical Care and Pain Clinic, Bellvitge University Hospital

University of Barcelona, Barcelona, Spain

Laura Contreras

Department of Anaesthesiology, Critical Care and Pain Clinic, Bellvitge University Hospital

University of Barcelona, Barcelona, Spain

Aline Defresne

University Department of Anesthesia and Intensive Care Medicine, Centre Hospitalier Regional de la Citadelle

Department of Anesthesia and Intensive Care Medicine, University Hospital of Liege

Anesthesia and Intensive Care Laboratory, GIGA-Consciousness Thematic Unit, GIGA-Research, Liege University, Liege, Belgium

Justin Delic      Department of Pharmacy, Cooper University Hospital, Camden, NJ, United States

Judith Dinsmore      Department of Anaesthesia, St. Georges University Hospital, London, United Kingdom

Gustavo Domeniconi      Sanatorio de la Trinidad San Isidro, Buenos Aires, Argentina

Hossam El Beheiry

Department of Anesthesiology and Pain Medicine, University of Toronto, Toronto

Department of Anesthesia, Trillium Health Partners, Mississauga, ON, Canada

Mazen Elwishi     Neuroanaesthesia & Critical Care, St George’s University Hospital, London, United Kingdom

Nicolai Goettel

University of Basel, Department of Clinical Research, Basel, Switzerland

University of Florida College of Medicine, Department of Anesthesiology, Gainesville, FL, United States

Nuno Veloso Gomes

University of Basel, Department of Clinical Research

University Hospital Basel, Department of Anesthesia, Prehospital Emergency Medicine and Pain Therapy, Basel, Switzerland

Benjamin F. Gruenbaum     Department of Anesthesiology and Perioperative Medicine, Mayo Clinic-Florida, Jacksonville, FL, United States

Shaun E. Gruenbaum     Department of Anesthesiology and Perioperative Medicine, Mayo Clinic-Florida, Jacksonville, FL, United States

Nidhi Gupta     Indraprastha Apollo Hospitals, New Delhi, Delhi, India

Laura Hemmer     Department of Anesthesiology, Northwestern University Feinberg School of Medicine, Chicago, IL, United States

Franziska Herpich     Departments of Neurology and Neurological Surgeries, Thomas Jefferson University Hospitals, Philadelphia, PA, United States

Theresa Human     Barnes-Jewish Hospital, Washington University, St. Louis, MO, United States

Amit Jain     Anesthesiology Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates

Madhan Jeyaraman

Indian Stem Cell Study Group, Lucknow

Department of Biotechnology, School of Engineering and Technology

Department of Orthopaedics, School of Medical Sciences and Research, Sharda University, Greater Noida, Uttar Pradesh, India

Indu Kapoor     Department of Neuroanaesthesiology and Critical Care, All India Institute of Medical Sciences (AIIMS), New Delhi, India

Ashish Khanna     Department of Anesthesiology, Section on Critical Care Medicine, Wake Forest School of Medicine, Winston-Salem, NC, United States

Matthew A. Kirkman     Department of Neurosurgery, Queen’s Medical Centre, Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom

Amanda Katherine Knutson     Department of Anesthesiology, Northwestern University Feinberg School of Medicine, Chicago, IL, United States

Ines P. Koerner     Anesthesiology & Perioperative Medicine and Neurological Surgery, Oregon Health & Science University, Portland, OR, United States

Tomer Kotek     Ben Gurion University of the Negev, Beersheba, Israel

Massimo Lamperti     Anesthesiology Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates

Ritesh Lamsal     Department of Anaesthesiology, Tribhuvan University Teaching Hospital, Institute of Medicine, Tribhuvan University, Kathmandu, Nepal

Kan Ma     Department of Anesthesiology and Pain Medicine, St. Michael's Hospital, University of Toronto, Canada

Charu Mahajan     Department of Neuroanaesthesiology and Critical Care, All India Institute of Medical Sciences (AIIMS), New Delhi, India

Jason M. Makii

Department of Pharmacy Services, University Hospitals Cleveland Medical Center

Case Western Reserve University School of Medicine, Cleveland, OH, United States

Hugues Marechal     Department of Anesthesia and Intensive Care Medicine, Centre Hospitalier Regional de la Citadelle, Liege, Belgium

Rohan Mathur     Division of Neurocritical Care, Departments of Anesthesiology and Critical Care Medicine, Neurology, and Neurosurgery, The Johns Hopkins University School of Medicine, Baltimore, MD, United States

Rajeeb Kumar Mishra     Department of Neuroanesthesia and Neurocritical Care, National Institute of Mental Health and Neurosciences, Bengaluru, India

Javier Montupil

University Department of Anesthesia and Intensive Care Medicine, Centre Hospitalier Regional de la Citadelle

Department of Anesthesia and Intensive Care Medicine, University Hospital of Liege

Anesthesia and Intensive Care Laboratory, GIGA-Consciousness Thematic Unit, GIGA-Research, Liege University, Liege, Belgium

Sathish Muthu

Indian Stem Cell Study Group, Lucknow

Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, Uttar Pradesh

Department of Orthopaedics, Government Medical College & Hospital, Dindigul, Tamil Nadu, India

Mehrnaz Pajoumand     Department of Pharmacy, University of Maryland Medical Center, Baltimore, MD, United States

Mariangela Panebianco     Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Clinical Sciences Centre for Research and Education, Liverpool, United Kingdom

Laura Pariente

Department of Anaesthesiology, Critical Care and Pain Clinic, Bellvitge University Hospital

University of Barcelona, Barcelona, Spain

Paolo Pelosi

Anesthesia and Intensive Care, San Martino Policlinico Hospital, IRCCS for Oncology and Neuroscience

Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Genoa, Italy

Hemanshu Prabhakar     Department of Neuroanaesthesiology and Critical Care, All India Institute of Medical Sciences (AIIMS), New Delhi, India

Vanitha Rajagopalan     Department of Neuroanaesthesiology and Critical Care, All India Institute of Medical Sciences, New Delhi, India

Chiara Riforgiato

Anesthesia and Intensive Care, San Martino Policlinico Hospital, IRCCS for Oncology and Neuroscience

Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Genoa, Italy

Chiara Robba

Anesthesia and Intensive Care, San Martino Policlinico Hospital, IRCCS for Oncology and Neuroscience

Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Genoa, Italy

Irene Rozet     Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, United States

Dona Saha     Department of Anaesthesiology and Critical Care, All India Institute of Medical Sciences Bhubaneswar, Bhubaneswar, Odisha, India

Shilpa Sharma

Department of Paediatric Surgery, All India Institute of Medical Sciences, New Delhi, Delhi

Indian Stem Cell Study Group, Lucknow, Uttar Pradesh, India

Michael J. Souter     Department of Anesthesiology and Pain Medicine, University of Washington, Harborview Medical Center, Seattle, WA, United States

Ljuba Stojiljkovic     Department of Anesthesiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States

Micheal Strein     Department of Pharmacotherapy and Outcomes Science, Virginia Commonwealth University, Richmond, VA, United States

Jose I. Suarez      Division of Neurocritical Care, Departments of Anesthesiology and Critical Care Medicine, Neurology, and Neurosurgery, The Johns Hopkins University School of Medicine, Baltimore, MD, United States

Veronica Taylor     Virginia Commonwealth University School of Pharmacy, Richmond, VA, United States

Jessica Traeger     Department of Pharmacy Services, University Hospitals Cleveland Medical Center, Cleveland, OH, United States

Swagata Tripathy     Department of Anaesthesiology and Critical Care, All India Institute of Medical Sciences Bhubaneswar, Bhubaneswar, Odisha, India

Abhay Tyagi     Department of Anesthesiology, St. Elizabeth’s Medical Center, Tufts University, Boston, MA, United States

Mayank Tyagi     Department of Neuroanaesthesiology and Critical Care, All India Institute of Medical Sciences (AIIMS), New Delhi, India

Jamie Uejima

Department of Anesthesiology, Northwestern University Feinberg School of Medicine, Chicago, IL, United States

Department of Anesthesiology and Pain Medicine, St. Michael’s Hospital, University of Toronto, Canada

Walter Videtta     Hospital Nacional Prof. A. Posadas, Buenos Aires, Argentina

Patrick Mark Wanner     University Hospital Basel, Department of Anesthesia, Prehospital Emergency Medicine and Pain Therapy, Basel, Switzerland

Alexander Zlotnik     Ben Gurion University of the Negev, Beersheba, Israel

Andres Zorrilla-Vaca

Department of Anesthesiology and Perioperative Medicine, University of Texas MD Anderson Cancer Center, Houston, TX

Department of Anesthesiology, Universidad Del Valle, Cali, Colombia

Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States

Acknowledgments

I thank the administration of the All India Institute of Medical Sciences (AIIMS), New Delhi (India), for allowing me to carry out this academic task. I also thank the faculty and staff of the Department of Neuroanaesthesiology and Critical Care at AIIMS, New Delhi, for their support. I specially thank Dr. Charu Mahajan and Dr. Indu Kapoor for their constructive criticism and inputs in this academic endeavor. Special thanks are due to the team of Elsevier—Melanie Tucker, Kristi Anderson, Susan Ikeda, Selvaraj Raviraj, and all those involved in this project.

Section A

Introduction

Chapter 1: Introduction to evidence-based practice

Indu Kapoor; Charu Mahajan; Hemanshu Prabhakar    Department of Neuroanaesthesiology and Critical Care, All India Institute of Medical Sciences (AIIMS), New Delhi, India

Abstract

Evidence-based medicine (EBM) is defined as explicit and judicious use of current best evidence in making decisions about the care of individual patients (Sackett et al., 1996). David M. Eddy first use the term evidence-based in 1987 in a manual commissioned by the Council of Medical Specialty Societies which was eventually published by the American College of Physicians (Eddy & American College of Physicians, 1992). He further discussed evidence-based policies in several other papers published in medical journals (Eddy, 1990a, 1990b). EBM requires the integration of the best research evidence, clinical expertise, and the patient’s distinctive conditions. The need for EBM is growing rapidly in health care practice because of many factors which include: increasing patient expectations, increased number of publications, information overload, and introduction of new technologies. The evidence obtained from research can be used either to improve clinical practice or to improve health service management. In situations where there is good quality evidence, the health care provider can give the best to the patient with minimal complications. However, in conditions where the evidence is poor, the decision-maker will have to depend on his/her experience, available resources, and patient’s expectations. Thus, evidence-based medicine is the backbone of health care facilities that provides a structured approach towards patient management.

Keywords

Evidence-based medicine; Neuroanesthesia; Cerebral perfusion pressure; Intracranial pressure; Decompressive craniectomy; Traumatic brain injury

Chapter outline

Introduction

Evidence-based practice in neuroanesthesia

References

Introduction

Evidence-based medicine (EBM) is defined as explicit and judicious use of current best evidence in making decisions about the care of individual patients (Sackett, Rosenberg, Gray, Haynes, & Richardson, 1996). David M. Eddy first use the term evidence-based in 1987 in a manual commissioned by the Council of Medical Specialty Societies which was eventually published by the American College of Physicians (Eddy & American College of Physicians, 1992). He further discussed evidence-based policies in several other papers published in medical journals (Eddy, 1990a, 1990b). EBM requires the integration of the best research evidence, clinical expertise, and the patient’s distinctive conditions. The need for EBM is growing rapidly in health care practice because of many factors which include: increasing patient expectations, increased number of publications, information overload, and introduction of new technologies. The evidence obtained from research can be used either to improve clinical practice or to improve health service management. In situations where there is good quality evidence, the health care provider can give the best to the patient with minimal complications. However, in conditions where the evidence is poor, the decision-maker will have to depend on his/her experience, available resources, and patient’s expectations. Thus, evidence-based medicine is the backbone of health care facilities that provides a structured approach towards patient management.

Evidence-based practice in neuroanesthesia

Recent times have witnessed a remarkable growth in the field of neuro-anesthesia techniques and monitoring with evolving research and publications. The good quality research which is on the top of the evidence pyramid including systematic reviews, meta-analysis, and randomized controlled trials (RCTs) is still very low on the list. On literature search, the data reveals a small fraction of work that has direct implications on clinical practice with little clinical significance. The majority of trials in neuro-anesthesia provide results with a low level of evidence. In the future, well-designed RCTs with large sample sizes may influence the neuro-anesthesia practice worldwide.

Cerebral perfusion pressure (CPP) and intracranial pressure (ICP) are the two main pillars in the treatment of neurosurgical patients who undergo anesthesia for surgery. As per current clinical evidence, the target ICP should be maintained <  22 mmHg (Level II B), the target CPP should be maintained between 60 and 70 mmHg (Level IIB) and CPP should never exceed >  70 mmHg (Level III) (Carney et al., 2017). The treatment of intracranial hypertension is either CPP targeted (Rosner’s concept) or ICP targeted or volume targeted (Lund’s concept) (Bullock et al., 1996; Eker, Asgeirsson, Grände, Schalén, & Nordström, 1998; Rosner, Rosner, & Johnson, 1995). At present there is a lack of evidence supporting the superiority of one approach over another. Among anesthetic agents, inhalational agents have vasodilatory effects on central nervous system vasculature in dose-dependent manner (Holmström & Akeson, 2004). Despite using it for many years, the use of nitrous oxide (N2O) is still debatable in neuro-anesthesia practice. The landmark trials-ENIGMA I and ENIGMA II had widely studied the effect of N2O on a large number of patients expected to undergo major surgery (Myles et al., 2007, 2014). In ENIGMA I trial authors concluded that the avoidance of N2O does not significantly affect the duration of hospital stay. Authors in the ENIGMA II trial supported the safety profile of N2O use in major non-cardiac surgery and did not show an increase in the risk of death and cardiovascular complications or surgical-site infection with its use (Myles et al., 2014). Neurosurgical cases in these trials contributed to a very small percentage of the study population. Thus, the result of these studies can’t be simply applied to neurosurgical patients. Further large RCTs would be required to find out the exact place of N2O in neuro-anesthesia field. The intravenous anesthetic agents have vasoconstrictive effects on the cerebral vasculature (Alkire et al., 1995). According to the Intraoperative Hypothermia For Aneurysm Surgery Trial (IHAST) data, thiopental or etomidate administration do not have any clinically significant demonstrable effect on postoperative neurologic outcomes in patients undergoing temporary clipping (Hindman, Bayman, Pfisterer, Torner, & Todd, 2010). Regarding the effect of hyperosmolar therapy, that is, mannitol or hypertonic saline on ICP, there is no conclusive evidence at present to support the superiority of one over another at reducing intracranial pressure in patients undergoing craniotomy for brain tumors (Prabhakar, Singh, Anand, & Kalaivani, 2014). Hyperventilation is one of the intraoperative strategies to provide a relaxed brain to the surgeon during craniotomy (Gelb et al., 2008). It has a short-term or temporary, but profound effect on cerebral blood flow (CBF). However, if used for a prolonged period, it has been shown to have a significantly worse outcomes than those were at the normal ventilatory rates (Muizelaar et al., 1991). Decompressive craniectomy (DC) is a neurosurgical procedure done to treat raised intracranial pressure (ICP) in patients with traumatic brain injury. DECRA trial (Decompressive Craniectomy in Diffuse Traumatic Brain Injury) showed that early DC is found to decrease ICP and the length of stay in intensive care unit (ICU), but is associated with more unfavorable functional outcomes (Cooper et al., 2011). At present, there is no evidence that DC can improve overall outcomes in adults. Regarding fluid resuscitation, the Saline versus Albumin Fluid Evaluation (SAFE) study was the first large multicentric RCT that showed no difference in the 28-day mortality rate between the saline and albumin groups (Finfer et al., 2004). The recommendation by the European Society of Intensive Care Medicine suggests that the colloids should not be used in patients with traumatic brain injury (TBI) (Reinhart et al., 2012). Regarding different neuroprotective strategies used in neurosurgical patients which include hypothermia, glycemic control, maintenance of mean arterial pressure, different anesthetic agents, and various other drugs, have no strong guidelines based on relevant clinical evidence. Most of the clinical evidence is weak due to the lack of large RCTs. According to Brain Trauma Foundation (BTF) 2016 guidelines, out of 15 parameters discussed, only steroids have level 1 recommendation against their use in TBI patients since their use in TBI patients leads to an increase in the mortality rate (Carney et al., 2017).

Many unresolved issues still exist in neuro-anesthesia practice worldwide. Though many trials have been done in recent times which show results that are of minimal clinical importance, an improved approach and methodology towards good research would be an answer to controversies revolving around inconclusive topics.

References

Alkire M.T., Haier R.J., Barker S.J., Shah N.K., Wu J.C., Kao Y.J. Cerebral metabolism during propofol anesthesia in humans studied with positron emission tomography. Anesthesiology. 1995;82(2):393–403 discussion 27A.

Bullock R., Chesnut R.M., Clifton G., Ghajar J., Marion D.W., Narayan R.K. Guidelines for the management of severe head injury. Brain Trauma Foundation. European Journal of Emergency Medicine: Official Journal of the European Society for Emergency Medicine. 1996;3(2):109–127.

Carney N., Totten A.M., O’Reilly C., Ullman J.S., Hawryluk G.W.J., Bell M.J. Guidelines for the management of severe traumatic brain injury, fourth edition. Neurosurgery. 2017;80(1):6–15. doi:10.1227/NEU.0000000000001432.

Cooper D.J., Rosenfeld J.V., Murray L., Arabi Y.M., Davies A.R., D’Urso P. Decompressive craniectomy in diffuse traumatic brain injury. The New England Journal of Medicine. 2011;364(16):1493–1502. doi:10.1056/NEJMoa1102077.

Eddy D.M. Clinical decision making: From theory to practice. Practice policies--guidelines for methods. JAMA. 1990a;263(13):1839–1841.

Eddy D.M. Clinical decision making: From theory to practice. Guidelines for policy statements: The explicit approach. JAMA. 1990b;263(16):2239–2240 2243.

Eddy D.M., American College of Physicians. In: David D.M., ed.A manual for assessing health practices & designing practice policies: The explicit approach. American College of Physicians; 1992.

Eker C., Asgeirsson B., Grände P.O., Schalén W., Nordström C.H. Improved outcome after severe head injury with a new therapy based on principles for brain volume regulation and preserved microcirculation. Critical Care Medicine. 1998;26(11):1881–1886.

Finfer S., Bellomo R., Boyce N., French J., Myburgh J., Norton R. A comparison of albumin and saline for fluid resuscitation in the intensive care unit. The New England Journal of Medicine. 2004;350(22):2247–2256.

Gelb A.W., Craen R.A., Rao G.S.U., Reddy K.R.M., Megyesi J., Mohanty B. Does hyperventilation improve operating condition during supratentorial craniotomy? A multicenter randomized crossover trial. Anesthesia and Analgesia. 2008. ;106(2):585–594. table of contents https://doi.org/10.1213/01.ane.0000295804.41688.8a.

Hindman B.J., Bayman E.O., Pfisterer W.K., Torner J.C., Todd M.M. No association between intraoperative hypothermia or supplemental protective drug and neurologic outcomes in patients undergoing temporary clipping during cerebral aneurysm surgery: Findings from the Intraoperative Hypothermia for Aneurysm Surgery Trial. Anesthesiology. 2010;112(1):86–101. doi:10.1097/ALN.0b013e3181c5e28f.

Holmström A., Akeson J. Desflurane increases intracranial pressure more and sevoflurane less than isoflurane in pigs subjected to intracranial hypertension. Journal of Neurosurgical Anesthesiology. 2004;16(2):136–143.

Muizelaar J.P., Marmarou A., Ward J.D., Kontos H.A., Choi S.C., Becker D.P. Adverse effects of prolonged hyperventilation in patients with severe head injury: A randomized clinical trial. Journal of Neurosurgery. 1991;75(5):731–739.

Myles P.S., Leslie K., Chan M.T.V., Forbes A., Paech M.J., Peyton P. Avoidance of nitrous oxide for patients undergoing major surgery: A randomized controlled trial. Anesthesiology. 2007;107(2):221–231.

Myles P.S., Leslie K., Chan M.T.V., Forbes A., Peyton P.J., Paech M.J. The safety of addition of nitrous oxide to general anaesthesia in at-risk patients having major non-cardiac surgery (ENIGMA-II): A randomised, single-blind trial. Lancet (London, England). 2014;384(9952):1446–1454.

Prabhakar H., Singh G.P., Anand V., Kalaivani M. Mannitol versus hypertonic saline for brain relaxation in patients undergoing craniotomy. The Cochrane Database of Systematic Reviews. 2014;7:CD010026doi:10.1002/14651858.CD010026.pub2.

Reinhart K., Perner A., Sprung C.L., Jaeschke R., Schortgen F., Johan Groeneveld A.B. Consensus statement of the ESICM task force on colloid volume therapy in critically ill patients. Intensive Care Medicine. 2012;38(3):368–383. doi:10.1007/s00134-012-2472-9.

Rosner M.J., Rosner S.D., Johnson A.H. Cerebral perfusion pressure: management protocol and clinical results. Journal of Neurosurgery. 1995;83(6):949–962.

Sackett D.L., Rosenberg W.M., Gray J.A., Haynes R.B., Richardson W.S. Evidence based medicine: What it is and what it isn’t. BMJ (Clinical Research Ed.). 1996;312(7023):71–72.

Section B

Neurophysiology

Chapter 2: ICP or CPP thresholds

Judith Dinsmorea; Mazen Elwishib    a Department of Anaesthesia, St. Georges University Hospital, London, United Kingdom

b Neuroanaesthesia & Critical Care, St George’s University Hospital, London, United Kingdom

Abstract

Monitoring the brain after injury plays a crucial role in the early detection of secondary adverse events, assessing response to treatment, and optimizing cerebral function. Intracranial pressure (ICP) and cerebral perfusion pressure (CPP) are the most commonly used modalities in neurocritical care. There remains a lack of evidence to support ICP and CPP monitoring but despite this their use remains fundamental to the care of patients with acute brain injury. Increased ICP and in particular refractory increased ICP and its burden—duration and intensity, are linked to adverse outcome. Advances in monitoring have led to the possibility of personalized medicine with individual targets such as CPPopt. Although prospective validation is lacking it appears that these individualized targets may have a stronger association with outcome than current consensus-based thresholds. The future management of acute brain injury will rely on an individual approach with continuous input from multiple monitors better predicting imminent secondary injury rather than ICP and CPP in isolation.

Keywords

Cerebrospinal fluid; Intracranial pressure; Traumatic brain injury; Cerebral perfusion pressure; Cerebral blood flow

Chapter Outline

Introduction

Question

What ICP threshold should we target and what is the optimal CPP range?

Controversy

Should ICP and CPP thresholds be protocolized according to consensus guidelines or individualized to achieve better outcomes?

Evidence

Consensus

Conclusion

References

Introduction

Monitoring the brain after injury plays a crucial role in the early detection of secondary adverse events, assessing response to treatment, and optimizing cerebral function. Intracranial pressure and cerebral perfusion pressure are the most commonly used modalities in neurocritical care.

The cranium is a rigid structure with a fixed internal volume containing the brain, cerebral blood, and cerebrospinal fluid (CSF). Under normal physiological conditions, the volume of the brain parenchyma is relatively constant and intracranial pressure (ICP) is derived primarily from the circulation of cerebral blood and CSF. The presence of a space-occupying lesion or an increase in the volume of any of the individual constituents necessitates the displacement of the others or an increase in ICP (the Monro-Kellie doctrine). Intracranial pressure has physiological values of 3–4 mmHg up to one year of age, and 10–15 mmHg in adults. However, the threshold for what is considered raised ICP or intracranial hypertension is dependent upon the individual pathology. In hydrocephalus, values over 15 mmHg are considered elevated whereas in traumatic brain injury (TBI) the threshold for intervention is typically 20–25 mmHg. Intracranial hypertension can have devastating complications. As ICP increases, cerebral perfusion begins to decrease with a reduction in cerebral blood flow (CBF). Eventually, compression of brain tissue against the tentorium, falx, and foramen magnum and ultimately herniation can occur. In addition to TBI, intracranial hypertension may complicate a range of other neurological conditions such as subarachnoid or intracerebral hemorrhage, ischemic stroke, meningitis, and hepatic encephalopathy. Intracranial hypotension can also occur usually secondary to CSF leakage.

Different methods are available to monitor ICP, but the two most commonly used methods are the use of an intraventricular catheter or an intraparenchymal micro-transducer device. The intraventricular catheter is considered the gold standard method as it measures global ICP in addition to allowing therapeutic drainage of CSF. Although the use of ICP monitoring varies between countries and centers, there are well-established indications and recommendations for its use in patients with TBI (Brain Trauma Foundation, 2020). Along with the direct measurement of pressure, ICP monitors are also used to guide clinical management and to calculate cerebral perfusion pressure (CPP). Additional information can be gained from analysis of the ICP waveform including the assessment of pressure-volume compensatory reserve and cerebrovascular pressure reactivity.

Cerebral perfusion pressure describes the pressure driving blood through the cerebrovascular bed and is calculated according to the equation: CPP = mean arterial pressure (MAP) − mean ICP. It is important to note that for accurate calculation the transducers measuring both MAP and ICP should be zeroed at the level of the foramen of Monro (Thomas, Czosnyka, & Hutchinson, 2015). The primary goal of an adequate CPP is to maintain CBF and tissue oxygenation. Recommendations for the optimal CPP threshold have changed over time. Current guidelines target a CPP between 60 and 70 mmHg with evidence of adverse outcomes at higher and lower values (Smith, 2015). When the CPP falls below 50 mmHg there is a risk of cerebral ischemia and aggravation of secondary brain injury. An individualized target for each patient has been proposed taking into account variables including age, sex, underlying pathology (Kirkman & Smith, 2014). Calculation of an optimal CPP for individual patients will need to consider cerebral autoregulation and cerebrovascular pressure reactivity.

Cerebral autoregulation is an important mechanism that allows the cerebral vascular system to maintain a relatively constant CBF despite changes in MAP and CPP. However, it is frequently impaired in brain injury. It is now possible to continuously monitor autoregulation using derived indices such as the cerebrovascular pressure reactivity index (PRx). This is a key component of cerebral autoregulation and determines the ICP response to changes in arterial blood pressure (ABP). When cerebrovascular pressure reactivity is defective such as in cases of TBI, a rise in MAP will lead to a passive increase in CBV and eventually a rise in ICP, whereas a drop in MAP will cause an opposite effect. PRx is calculated as a correlation coefficient between the slow waves of MAP and ICP at sequential time-averaged points over a defined period. Negative values, where ABP is negatively correlated with ICP, or values around zero, indicate intact autoregulation. Positive values suggest disturbed reactivity or impaired autoregulation. The concept of an individualized or optimum CPP (CPPopt) is based on the observation that PRx and CPP exhibit a U-shaped relationship with time. The PRx is at its lowest value where cerebrovascular reactivity is best preserved, and this corresponds to the CPPopt (Fig. 2.1). Continuous cerebrovascular reactivity monitoring could therefore be used to derive individualized targets such as optimum CPP (CPPopt) and patient-specific ICP thresholds (Zeiler et al., 2020).

Fig. 2.1

Fig. 2.1 Illustration of CPPopt determination with the upper and lower ends of autoregulation. Illustration of CPPopt determination with the upper and lower ends of autoregulation. Curve a: U-shaped PRx -CPP curve showing automated CPPopt. The PRx threshold is set for 0.3 for impaired autoregulation (white line) . The intersection with the U-shaped curve marks both the upper and lower reactivity CPP values. Curve b: PRx-CPP curve with PRx threshold set at 0.0 for impaired autoregulation. The result is a smaller CPP range for upper and lower reactivity CPP values. (With thanks to Zeiler, F. A., Ercole, A., Czosnyka, M., Smielewski, P., Hawryluk, G., Hutchinson, P. J. A., Menon, D. K., & Aries, M. (2020). Continuous cerebrovascular reactivity monitoring in moderate/severe traumatic brain injury: A narrative review of advances in neurocritical care. British Journal of Anaesthesia, 124(4), 440–453. https://doi:10.1016/j.bja.2019.11.031.)

Question

What ICP threshold should we target and what is the optimal CPP range?

Setting physiological parameters and treatment thresholds is part of good critical care and protocol-based treatment strategies appear to improve morbidity and mortality outcomes (Helmy, Vizcaychipi, & Gupta, 2007). Most current treatment strategies aim to maintain a single target threshold for ICP or a range for CPP; thresholds are based on analysis of data derived from populations of patients with TBI (Brain Trauma Foundation, 2020). The Brain Trauma Foundation (BTF) guidelines for the management of severe TBI have been widely adopted across the globe. In the 4th edition, the ICP treatment threshold was set at 22 mmHg based on the available evidence which indicated increased mortality with sustained higher ICP levels. The CPP threshold was set at 60–70 mmHg with evidence of significant harm with CPP < 50 mmHg and adverse outcomes with CPP >  70 mmHg (Table 2.1).

Table 2.1

Brain Trauma Foundation Guidelines (BTF)—4th Edition showing recommendations for intracranial pressure (ICP) and cerebral perfusion pressure (CPP) with the level of evidence.

Controversy

Should ICP and CPP thresholds be protocolized according to consensus guidelines or individualized to achieve better outcomes?

Although the use of single target thresholds provides a useful starting point for patient management, the evidence for this approach is inconsistent (Helbok, Meyfroidt, & Beer, 2018; Kirkman & Smith, 2014; Smith, 2018). In addition, single target thresholds fail to account for either heterogeneity of injury type or individual patient response to treatment (Younsi et al., 2017). An individualized approach using multimodality monitoring to target each patient could be used in other types of acute brain injury such as intracerebral and subarachnoid hemorrhage in addition to TBI. As the technology has evolved, clinicians now can personalize patient care using models for predicting optimal CPP and ICP thresholds. There is some evidence that these individual targets may be associated with better outcomes than existing consensus guidelines (Zeiler et al., 2020). However, these prediction models currently come from single center studies, albeit with multicenter validation studies, and large-scale prospective validation is still required. In addition, global adoption of such individualized approaches will require major investments in monitoring equipment and software packages that may not be widely available.

Evidence

Despite the widespread use of ICP and CPP guided therapy, there is no high-quality evidence for outcome benefit. Most studies have investigated patients with TBI and results are inconsistent (Bragge et al., 2016). This is in part due to the difficulties involved in conducting prospective randomized controlled trials (RCT) in this area but also to the fact that TBI is not a single pathophysiological entity; rather it represents a heterogeneous set of disease processes each requiring different approaches to both diagnosis and management. In the absence of robust evidence, consensus guidelines dictate practice and of these, the BTF guidelines are considered the gold standard. There is evidence of adverse outcomes, specifically excess mortality in those patients with refractory intracranial hypertension (Badri et al., 2012). However, there is insufficient evidence to provide Level I or Level IIa recommendations for ICP thresholds. The current BTF recommendation is to treat ICP > 22 mmHg (Level IIb). Although some meta-analyses of ICP targeted care have reported treatment benefits (Stein, Georgoff, Meghan, Mirza, & El Falaky, 2010; Zhao et al., 2016), others have suggested it might be associated with a worse outcome (Su & Wang, 2014; Yuan et al., 2015). The only prospective RCT, the BEST-TRIP trial, came from South America (Chesnut et al., 2012). This showed no difference in 3-6-month outcome between those patients who had ICP targeted therapy when compared to patients whose management was based on clinical assessment and imaging. However, differences in patient care before hospital admission and after discharge were not reported and there have been concerns about the generalizability to routine practice in higher-income countries.

There is also little evidence from RCTs to support a specific CPP threshold or range and recommendations have changed over time. The BTF recommends using CPP to decrease 2-week mortality in severe TBI and current guidelines set the CPP threshold at 60-70 mmHg. There is evidence of significant harm with CPP < 50 mmHg and adverse outcomes with CPP >  70 mmHg. Higher CPP values (>  70 mmHg) had been previously advocated due to the perceived physiological advantages of increased perfusion. However, outcomes were not improved and there appeared to be a potential to cause harm with the increased fluid volumes and vasopressor or inotrope use required to maintain CPP linked to a fivefold increase in the frequency of acute lung injury (Robertson et al., 1999). In the absence of high-quality evidence for single ICP and CPP targets, the use of more dynamic, individualized CPP and ICP thresholds have been proposed.

To determine optimal CPP and ICP at an individual level both cerebral autoregulation and cerebral vascular reactivity need to be considered. Various studies have evaluated the use of continuously monitored PRx. As described previously, the U-shaped curve obtained by plotting the PRx index against CPP forms the basis for individualized or optimal CPP targets. It appears that individual CPPopt thresholds can be identified in about 65% of TBI patients with both the upper (hyperperfusion) and lower extremes (hypoperfusion) associated with worse cerebral vascular reactivity (Steiner et al., 2002). A 24-h period of dynamic monitoring seems sufficient to determine the optimal CPP. Importantly, the optimal CPP threshold appears to be dynamic; specific for individual patients but also varying at different time points in response to changing physiology. Retrospective data support a strong association between failure to achieve CPPopt and unfavorable outcomes (Aries et al., 2015). It was also noted that hypoperfusion was associated with higher mortality and hyperperfusion with more severe disability. Prospective evaluation of CPPopt guided therapy is still awaited although a recommendation for its use has been made albeit with only moderate quality of evidence (Puppo et al., 2014). A feasibility study (COGiTATE) to assess the use of CPPopt guided management is currently ongoing.

The concept of an individual ICP treatment threshold, using continuously monitored cerebrovascular reactivity with PRx, has also been proposed. Although work is in its early stages, two studies appear to demonstrate a stronger association between outcome and time spent above individual ICP thresholds when compared to the existing BTF ICP thresholds. In the first of these studies, individual ICP thresholds were identified by plotting PRx against ICP. The ICP threshold is determined as the ICP value that corresponds to a PRx value of +  0.20 and where all subsequent higher ICP values have persistent PRx values > +  0.20. There was a statistically significant correlation between hourly ICP dose above the individual threshold and outcome at 6 and 12 months when compared to hourly ICP dose above 20 and 22 mmHg (BTF thresholds) (Christos et al., 2014). The prospective multicenter CENTER TBI High-Resolution ICU sub-study used semi-automated algorithmic detection of individual ICP thresholds using similar criteria to the above study (Steiner et al., 2002; Zeiler et al., 2019). The mean hourly dose of ICP above a patient’s individual ICP threshold was more strongly associated with mortality compared to the dose above the BTF threshold of 22 mmHg. However, this work is very much in its infancy and currently remains a research tool. A moving correlation coefficient named RAP indicates the relationship between ICP and amplitude of ICP pulse waveforms. RAP has values close to 0 when compensatory reserve is good, increasing to values closer to +  1 when the compensatory mechanisms are exhausted such as in severe TBI. A weighted ICP can then be derived as wICP = (1 − RAP) × ICP. A CENTER TBI validation study reported that wICP displayed a better association with outcome and mortality rates when compared to mean ICP. This provides a promising scope for research but is currently an experimental concept and further studies are needed to identify wICP treatment thresholds.

Consensus

In the current absence of high-quality evidence, expert recommendations and consensus statements are considered valuable tools to guide clinical practice. The latest edition of the BTF reviewed all the available evidence and advised thresholds for blood pressure, ICP and CPP. These thresholds may be considered values to avoid to reduce the possibility of adverse outcomes or values to achieve to improve the likelihood of a positive outcome or a value that triggers a change in treatment. See Table 2.1. Recommendations for the use of ICP monitoring and management options for treatment of elevated ICP guidelines have also been produced by other expert groups but these do not specify ICP thresholds (Christos et al., 2014; Koskinen et al., 2014). The Neurocritical Care Society and the European Society of Intensive Care Medicine have produced recommendations for multimodality monitoring in neurocritical Care which include the use of ICP and CPP. These do not support the use of a single threshold for ICP (Puppo et al., 2014).

Conclusion

There remains a lack of evidence to support ICP and CPP monitoring but despite this, their use remains fundamental to the care of patients with acute brain injury. Increased ICP and in particular refractory increased ICP and its burden—duration and intensity, is linked to adverse outcomes. Although most commonly used for the management of TBI, monitoring provides useful information in other conditions such as subarachnoid and intracerebral hemorrhage. Despite existing consensus guidelines, thresholds for intervention are uncertain. It is increasingly recognized that reliance on single thresholds for all patients is an oversimplification. Targets and thresholds will vary both within and between patients depending upon time, specific pathology, and individual response to injury. Advances in monitoring have led to the possibility of personalized medicine with individual targets such as CPPopt. Although prospective validation is lacking it appears that these individualized targets may have a stronger association with the outcome than current consensus-based thresholds. The future management of acute brain injury will rely on an individual approach with continuous input from multiple monitors better predicting imminent secondary injury rather than ICP and CPP in isolation.

References

Aries M.J.H., Van Der Naalt J., van den Bergh W.B., van Dijk M., Elting J.W.J., Czosnyka M., et al. Neuromonitoring of patients with severe traumatic brain injury at the bedside. Netherlands Journal of Critical Care. 2015. ;20(2):6–12. http://njcc.nl/sites/default/files/pdf/review_10.pdf.

Badri S., Chen J., Barber J., Temkin N.R., Dikmen S.S., Chesnut R.M., et al. Mortality and long-term functional outcome associated with intracranial pressure after traumatic brain injury. Intensive Care Medicine. 2012;38(11):1800–1809. doi:10.1007/s00134-012-2655-4.

Bragge P., Synnot A., Maas A.I., Menon D.K., Cooper D.J., Rosenfeld J.V., et al. A state-of-the-science overview of randomized controlled trials evaluating acute management of moderate-to-severe traumatic brain injury. Journal of Neurotrauma. 2016;33(16):1461–1478. doi:10.1089/neu.2015.4233.

Brain Trauma Foundation. Guidelines for the management of severe TBI. 4th Ed. Brain Trauma Foundation; 2020. Retrieved from https://braintrauma.org/guidelines/guidelines-for-tthe-management-of-severe-tbi-4th-ed#/.

Chesnut R.M., Temkin N., Carney N., Dikmen S., Rondina C., Videtta W., et al. A trial of intracranial-pressure monitoring in traumatic brain injury. New England Journal of Medicine. 2012;367:2471–2481. doi:10.1056/nejmoa1207363.

Christos L., De Santis S.M., Smielewski P., Menon D.K., Hutchinson P., Pickard J.D., et al. Patient-specific thresholds of intracranial pressure in severe traumatic brain injury. Journal of Neurosurgery. 2014;120:893–900. doi:10.3171/2014.1.jns131292.

Helbok R., Meyfroidt G., Beer R. Intracranial pressure thresholds in severe traumatic brain injury: Con: The injured brain is not aware of ICP thresholds!. Intensive Care Medicine. 2018;44(8):1318–1320. doi:10.1007/s00134-018-5249-y.

Helmy A., Vizcaychipi M., Gupta A.K. Traumatic brain injury: Intensive care management. British Journal of Anaesthesia. 2007;99(1):32–42. doi:10.1093/bja/aem139.

Kirkman M.A., Smith M. Intracranial pressure monitoring, cerebral perfusion pressure estimation, and ICP/CPP-guided therapy: A standard of care or optional extra after brain injury?. British Journal of Anaesthesia. 2014;112(1):35–46. doi:10.1093/bja/aet418.

Koskinen L.O., Latronico N., Maas A.I.R., Payen J.F., Rosenthal G., Sahuquillo J., et al. Clinical applications of intracranial pressure monitoring in traumatic brain injury: Report of the Milan consensus conference. In: Acta neurochirurgica. Springer-Verlag Wien; 1615–1622. doi:10.1007/s00701-014-2127-4. 2014;Vol. 156.

Puppo C., Riker R., Robertson C., Schmidt M., Taccone F., Naidech A., et al. Consensus summary statement of the international multidisciplinary consensus conference on multimodality monitoring in Neurocritical care: A statement for healthcare professionals from the neurocritical care society and the European Society of Intensive Care Medicine. Intensive Care Medicine. 2014;40(9):1189–1209. doi:10.1007/s00134-014-3369-6.

Robertson C.S., Valadka A.B., Hannay H.J., Contant C.F., Gopinath S.P., Cormio M., et al. Prevention of secondary ischemic insults after severe head injury. Critical Care Medicine. 1999;27(10):2086–2095. doi:10.1097/00003246-199910000-00002.

Smith M. Cerebral perfusion pressure. British Journal of Anaesthesia. 2015;115(4):488–490. doi:10.1093/bja/aev230.

Smith M. Multimodality Neuromonitoring in adult traumatic brain injury: A narrative review. Anesthesiology. 2018;128(2):401–415. doi:10.1097/ALN.0000000000001885.

Stein S.C., Georgoff P., Meghan S., Mirza K.L., El Falaky O.M. Relationship of aggressive monitoring and treatment to improved outcomes in severe traumatic brain injury. Journal of Neurosurgery. 2010;112(5):1105–1112. doi:10.3171/2009.8.JNS09738.

Steiner L.A., Czosnyka M., Piechnik S.K., Smielewski P., Chatfield D., Menon D.K., et al. Continuous monitoring of cerebrovascular pressure reactivity allows determination of optimal cerebral perfusion pressure in patients with traumatic brain injury. Critical Care Medicine. 2002;30(4):733–738. doi:10.1097/00003246-200204000-00002.

Su H., Wang F. The effects of intracranial pressure monitoring in patients with traumatic brain injury. PLoS One. 2014;9(2):e87432.

Thomas E., Czosnyka M., Hutchinson P. Calculation of cerebral perfusion pressure in the management of traumatic brain injury: Joint position statement by the councils of the Neuroanaesthesia and Critical Care Society of Great Britain and Ireland (NACCS) and the Society of British Neurological Surgeons (SBNS). British Journal of Anaesthesia. 2015;115(4):487–488. doi:10.1093/bja/aev233.

Younsi A., Zaaroor M., Zelinkova V., Zemek R., Zumbo F., Winkler M.K.L., et al. Traumatic brain injury: Integrated approaches to improve prevention, clinical care, and research. The Lancet Neurology. 2017;16(12):987–1048. doi:10.1016/S1474-4422(17)30371-X.

Yuan Q., Wu X., Sun Y., Yu J., Li Z., Du Z., et al. Impact of intracranial pressure monitoring on mortality in patients with traumatic brain injury: A systematic review and meta-analysis. Journal of Neurosurgery. 2015;122(3):574–587. doi:10.3171/2014.10.JNS1460.

Zeiler F.A., Ercole A., Cabeleira M., Beqiri E., Zoerle T., Carbonara M., et al. Patient-specific ICP epidemiologic thresholds in adult traumatic brain injury. Journal of Neurosurgical Anesthesiology. 2019;33:28–38. doi:10.1097/ANA.0000000000000616.

Zeiler F.A., Ercole A., Czosnyka M., Smielewski P., Hawryluk G., Hutchinson P.J.A., et al. Continuous cerebrovascular reactivity monitoring in moderate/severe traumatic brain injury: A narrative review of advances in neurocritical care. British Journal of Anaesthesia. 2020;124(4):440–453. doi:10.1016/j.bja.2019.11.031.

Zhao S., Yan R., Su Z., Qiu S., Xu J., Zhou Y., et al. Effects of intracranial pressure monitoring on mortality in patients with severe traumatic brain injury: A meta-analysis. PLoS One. 2016;11(12):doi:10.1371/journal.pone.0168901.

Chapter 3: Role of hypothermia

Franziska Herpicha; Theresa Humanb; Mehrnaz Pajoumandc    a Departments of Neurology and Neurological Surgeries, Thomas Jefferson University Hospitals, Philadelphia, PA, United States

b Barnes-Jewish Hospital, Washington University, St. Louis, MO, United States

c Department of Pharmacy, University of Maryland Medical Center, Baltimore, MD, United States

Abstract

The origins of targeted temperature management (TTM) date back to 1940 and renewed interest in the modern era has produced data in various neurologic conditions, becoming a cornerstone for neuroprotective strategies. Despite conflicting results from clinical trials, TTM is still used as an intervention to treat secondary brain damage and remains a critical intervention in patients experiencing an acute neurologic injury. Controversy still exists as to what diseases TTM should be considered, what temperature should be targeted, what devices are most effective with the least complications, and what duration is most effective.

Keywords

Hyperthermia; Intracerebral hemorrhage; Targeted temperature management; Prophylactic hypothermia; Traumatic brain injury; Intracranial cerebral pressure

Chapter outline

Introduction

What disease states should target temperature management be considered?

Cardiac arrest

Acute ischemic stroke

Intracerebral hemorrhage

Aneurysmal subarachnoid hemorrhage

Traumatic brain injury

Spinal cord injury

Status epilepticus

Bacterial meningitis

Acute liver failure

Is one method of cooling superior?

What is the optimal target temperature?

Cardiac arrest

Traumatic brain injury

Does time to TTM implementation change outcomes?

What is the optimal duration of TTM to improve outcomes?

What is the optimal rate of rewarming to improve patient outcomes and prevent complications?

Is there an optimal method/protocol to detect and treat shivering?

The Columbia antishivering protocol

Non-pharmacologic management of shivering

Pharmacologic management of shivering

What are the important complications to evaluate during TTM?

Cardiovascular

Infections

Bleeding

Laboratory

Skin integrity

Consensus statement

What disease states should target temperature management be considered?

Is one method of cooling superior?

What is the optimal target temperature?

Does time to TTM implementation change outcomes?

What is the optimal duration of TTM to improve outcomes?

What is the optimal rate of rewarming to improve patient outcomes and prevent complications?

Is there an optimal method/protocol to detect and treat shivering associated with TTM?

What are the important complications to evaluate during TTM?

Conclusion

References

Introduction

The origins of targeted temperature management (TTM) date back to 1940 and renewed interest in the modern era has produced data in various neurologic conditions, becoming a cornerstone for neuroprotective strategies (Benson, Williams Jr., Spencer, & Yates, 1959; Fay, 1945). Despite conflicting results from clinical trials, TTM is still used as an intervention to treat secondary brain damage and remains a critical intervention in patients experiencing an acute neurologic injury. Controversy still exists as to what diseases TTM should be considered, what temperature should be targeted, what devices are most effective with the least complications, and what duration is most effective.

What disease states should target temperature management be considered?

Cardiac arrest

Early investigations established that hyperthermia after cardiac arrest (CA) is associated with poor outcomes (Bro-Jeppesen, Hassager, Wanscher, et al., 2013; Leary, Grossestreuer, Iannacone, et al., 2013; Zeiner, Holzer, Sterz, et al., 2001). Two landmark trials published in the early 2000s demonstrated the neuroprotective effects of therapeutic hypothermia (TH) after CA, thereby informing the use of TTM in this patient population for years to come. In the Hypothermia after Cardiac Arrest (HACA) trial, 275 comatose survivors of out-of-hospital ventricular fibrillation CA were randomized to mild hypothermia (target temperature 32°C–34°C) for 24 h(Hypothermia after Cardiac Arrest Study Group, 2002). Results demonstrated that 55% of patients in the hypothermia group had a favorable neurologic outcome at 6 months, defined as independence with moderate to no disability, as compared to 39% in the normothermia group (RR 1.40; 95% CI, 1.08–1.81; p = 0.009). Furthermore, the hypothermia group had lower mortality compared to normothermia, 41% compared to 55% respectively (RR 0.74; 95% CI, 0.58–0.95; p = 0.02). Bernard et al. randomized 77 comatose survivors of out-of-hospital ventricular fibrillation cardiac arrest to hypothermia (33°C) or normothermia (Bernard, Gray, Buist, et al., 2002). 49% (21 of 43) of patients in the hypothermia group had a good outcome and were either discharged home or to a rehab facility as compared to 26% (9 of 34) of patients in the normothermia group (p = 0.046). A limitation of both trials is that temperature was not tightly maintained in the control groups.

Acute ischemic stroke

The effects of hyperthermia after acute ischemic stroke (AIS) have been investigated and have consistently been associated with poor clinical outcomes (Greer, Funk, Reaven, Ouzounelli, & Uman, 2008; Saini, Saqqur, Kamruzzaman, Lees, & Shuaib, 2009). Su et al. randomized patients with massive cerebral hemispheric infarction to hypothermia (33°C or 34°C) or normothermia (Su, Fan, Zhang, et al., 2016). Although underpowered, the results demonstrated no difference in the primary mortality outcome however mild hypothermia may improve neurologic outcomes at 6 months, as evaluated by modified Rankin score.

The more recent randomized open-label clinical trial (EuroHYP-I) compared 3-month functional outcomes of patients with AIS when randomized to hypothermia (34°C or 35°C) or standard treatment alone (van der Worp, Macleod, Bath, et al., 2014). The results did not demonstrate any difference in outcomes although only 98 of the originally intended 1500 patients were included as the trial was discontinued due to slow recruitment and termination of funding.

A prospective randomized study comparing the safety and clinical outcome of hemicraniectomy alone with combination therapy (hemicraniectomy and hypothermia of 35°C) in malignant brain infarction, suggested an improvement in functional outcome with combination therapy (Els et al., 2006). Therefore, the Decompressive surgery plus hypothermia for space-occupying stroke (DEPTH-SOS) trial was conducted to evaluate the effects and safety of moderate hypothermia (33°C ± 1°C) for at least 72 h compared to standard care after hemicraniectomy in patients with malignant stroke (Neugebauer, Schneider, Bosel, et al., 2019). The trial was stopped for safety reasons after enrollment of 50 patients as there was a trend toward a higher rate of significant adverse events within 14 days in the hypothermia group, that persisted at 12 months follow-up. In fact, the combination may be potentially harmful.

Intracerebral hemorrhage

Hyperthermia in intracerebral hemorrhage (ICH) has been associated with hematoma growth and poor outcome at 90 days (Rincon, Lyden, & Mayer, 2013). Several small studies examined the effects of mild hypothermia compared to controls and found perihematomal edema volume remained stable in the hypothermia group, while it significantly increased in the control group (Kollmar et al., 2010; Staykov et al., 2013). A retrospective case-control study evaluating normothermia to treat fever after ICH was associated with increased duration of sedation, mechanical ventilation, and ICU stay and not associated with improved discharge functional outcome (Lord, Karinja, Lantigua, et al., 2014). These results bring into question the benefit of fever control with TTM in ICH, which introduces its own set of risks.

Aneurysmal subarachnoid hemorrhage

Fever is associated with an increased risk of death, vasospasm, and poor outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH) (Gowda, Jaffa, & Badjatia, 2018; Oliveira-Filho, Ezzeddine, Segal, et al., 2001). Intraoperative hypothermia was investigated as early as 1955 as adjunctive therapy during surgery to secure a ruptured aneurysm. The Intraoperative Hypothermia for Aneurysm Surgery Trial (IHAST) was a multicenter, prospective, randomized trial, that evaluated outcomes in those that underwent intraoperative hypothermia (33°C) compared to normothermia (36.5°C) (Todd, Hindman, Clarke, & Torner, 2005). The study failed to demonstrate significant differences between the groups to duration of ICU and hospital stay, rates of death, discharge disposition, or functional outcome. However, the incidence of postoperative bacteremia was significantly higher in the hypothermia group.

A case-control study in 40 consecutive febrile patients compared to 80 historical controls evaluated the impact of induced normothermia (37°C) on outcome following aSAH. A multivariable linear regression model showed that induced normothermia was associated with improved outcomes at 1 year.

Few retrospective case series have investigated the effect of TTM during the acute phase of aSAH with poor grade WFNS (Anei, Sakai, Iihara, & Nagata, 2010; Nagao, Irie, Kawai, et al., 2000; Nakamura, Tatara, Morisaki, Kawakita, & Nagao, 2002; Yasui, Kawamura, Suzuki, Hadeishi, & Hatazawa, 2002). Overall outcomes results were unsatisfactory with mortality rates of 47%–67% and favorable outcomes as low as 5%–44%. Anei et al. compared outcomes before and after the introduction of HT at their institution and found no difference in mortality between groups (Anei et al., 2010). Gasser et al. however showed more promising results in patients with aSAH WFNS 4 to 5 who received TH after developing refractory intracranial hypertension (Gasser, Khan, Yonekawa, Imhof, & Keller, 2003). TH was initiated on day 4.2 ± 3.3 and continued for 4.3 ± 3.9 days. 47.6% (10 of 21) had favorable GOS (4, 5), however, cooling for more than 72 h was associated with more complications.

Seule et al. evaluated 100 aSAH patients that received TH, of which 28 patients had symptomatic vasospasm refractory to hypertensive and endovascular therapies (Seule, Muroi, Mink, Yonekawa, & Keller, 2009). The mean duration of TH was 5.7 ± 3.3 days. Although 57% of the patients had a poor-grade aSAH, a favorable outcome (GOS 4–5) was achieved in 57% of patients. Of patients with refractory intracranial hypertension, a favorable outcome was obtained in 25%. Of note, 23 of the 28 patients with vasospasm were treated concomitantly with TH and barbiturate coma which could skew the results significantly.

Traumatic brain injury

The use of prophylactic hypothermia to prevent secondary brain injury after traumatic brain injury (TBI) has been evaluated in multiple studies. While earlier trials demonstrated the benefit of prophylactic hypothermia, larger trials failed to do so (Clifton, Allen, Barrodale, et al., 1993; Clifton, Miller, Choi, et al., 2001; Clifton, Valadka, Zygun, et al., 2011; Maekawa, Yamashita, Nagao, Hayashi, & Ohashi, 2015; Polderman et al., 2002; Smrcka, Vidlak, Maca, Smrcka, & Gal, 2005). The Prophylactic Hypothermia Trial to Lessen Traumatic Brain Injury-Randomized Clinical Trial (POLAR-RCT) compared prophylactic hypothermia (33°C–35°C sustained for at least 72 h and up to 7 days) to normothermia and found no difference in neurological outcomes and mortality at six months (Cooper, Nichol, Bailey, et al., 2018). Of note, 13% of patients in the hypothermia group failed to reach the target temperature (TT) and 19% were withdrawn early.

TT for refractory intracranial cerebral pressure (ICP) management was evaluated in a small randomized trial which resulted in significant reductions in cerebral blood flow and cerebral metabolic rate of oxygen (Shiozaki, Sugimoto, Taneda, et al., 1993). The European Study of Therapeutic Hypothermia (32°C–35°C) for Intracranial Pressure Reduction after Traumatic Brain Injury (the EUROTHERM3235 Trial) was stopped early due to safety concerns, demonstrating worse outcomes with hypothermia compared to normothermia (Andrews, Sinclair, Rodriguez, et al., 2015).

Spinal cord injury

Two approaches to TH in acute spinal cord injury (SCI) include local and systemic cooling. Local hypothermia focuses on cooling only the region of the injury or spinal cord, whereas systemic hypothermia focuses on cooling the core temperature of the body. A