Preface

The re-discovering of ketamine in anesthesia and other medical disciplines cannot be understood without a timeline. In the 1980s, ketamine was reserved for veterinary and experimental animal studies. During my early research years, I used ketamine for anaesthetizing rats, cats, and monkeys. Unfortunately, some people began using ketamine irresponsibly as a recreational drug. As such, ketamine was considered a dangerous substance more than a medication to be used in anesthesia.

Phencyclidine (PCP) was synthesized in 1956 and soon was used in human trials. However, sometimes its psychotic excitatory effects made patients unmanageable in the postoperative period, so it was removed from the anesthetic armamentarium for humans. Other phencyclidine derivatives were synthesized, but ketamine (a ketone plus an amine) outperformed the others, as it retained analgesic and anesthetic action with no hypnotic effects. In the 1970s, some PCP derivatives were considered illegal drugs, while ketamine, although approved, was only used by certain groups (including the military during the Vietnam War) because its psychedelic effects (e.g., hallucinations) were considered unacceptable by most of the scientific community. The introduction of diazepam, droperidol, or chlorpromazine minimized those adverse effects. However, concomitant use of those drugs did extend the use of ketamine as a drug of abuse, but not its use in regular Anesthesia. Hence its bad reputation.

In the 1990s, the arrival of new intravenous hypnotics such as propofol almost relegated ketamine to the drawer of oblivion in the clinical setting. But there were many research groups dedicated to studying NMDA calcium channels, NMDA receptor blockade drugs, and NMDA-receptor glutamatergic phenomena. Investigation of analgesia pathways and mechanisms originated new knowledge on mu and other opioid receptors, including evidence that opioids could open NMDA receptors and induce opioid-induced hyperalgesia.

In the new century, management of both acute and chronic pain has attracted great interest. Our modern society does not accept any suffering, including pain, depression, schizophrenia, or other disabling conditions, and the medical community agrees. Thus, it is the perfect time to re-examine ketamine.

The last twenty years have witnessed a renaissance of ketamine. Deep knowledge of pharmacokinetics and pharmacodynamics has led to a better understanding of different administration routes and how to manage the drug. The synthesis of isomers and derivatives has unveiled new uses, for example, in psychiatry. The usefulness of ketamine in war, in developing countries, and as premedication in children, has regained interest in other populations and situations.

This book provides a comprehensive overview of ketamine. It includes a discussion of NMDA receptors, the use of ketamine in anesthesia and pain disorders, the clinical non-anesthetic uses of ketamine (especially in depression), and special situations that will benefit from ketamine, such as palliative care and the trauma suite.

The book ends with a review on the use of ketamine in low-resource countries and examines the current illicit use of the drug.

We hope this book reaches young healthcare professionals and helps to eradicate the fear and misgivings associated with the use of ketamine.

## **Dr. Nieves Saiz-Sapena, MD, Ph.D. and Dr. Manuel Granell-Gil, MD, Ph.D.** Department of Anesthesiology, Critical Care and Pain Clinic, Consortium General University Hospital of Valencia, Valencia, Spain

Section 1 Introduction

## **Chapter 1**
