Anesthesiologist

From Wikipedia, the free encyclopedia

Occupation
Names	Anesthesiologist (US English) Anaesthetist (British English)
Profession
Activity sectors	Medicine, science
Description
Education required	See selection and training
Fields of employment	Science, healthcare, research and development
Related jobs	Physician

An anesthesiologist is a physician [MD/DO] trained in anesthesia and perioperative medicine.

The title of the role varies between countries. In countries following the practice of North America, those specializing in the field are termed anesthesiologists, but in the United Kingdom and current or former member countries of the Commonwealth of Nations, such providers use the title anesthetist instead.

The length and format of training may vary from country to country. For physicians, a four-year residency is required after four years of medical school training to be awarded a medical degree. A four year bachelors degree is required before medical school for a total of 12 years of education. Many anesthesiologists do an additional fellowship year to subspecialize in critical care medicine, cardiac, pediatric, obstetric, or regional anesthesia. Anesthesiologists in training spend this time gaining experience in various different subspecialties of anesthesiology and undertake various advanced postgraduate examinations and skill assessments. These lead to the award of a specialist qualification at the end of their training indicating that they are an expert in the field.

During preoperative evaluation, in consultation with the surgical team, anesthesiologists create an anesthetic plan tailored to each individual patient taking into consideration the patient’s medical history and the type of surgical procedure planned. This may include invasive monitoring (TEE, CVP, arterial pressure), neuraxial nerve blocks (spinal or epidural), peripheral nerve blocks (selectively anesthetizing a specific part of the body), and/or various levels of sedation including reversible unconsciousness known as “General Anesthesia.” Anesthesiologists are acute care specialists and as such provide intensive care techniques perioperatively as the experts of airway management, intraoperative life support, pain control, intraoperative diagnoses, stabilization, and proper postoperative medical management of patients. An anesthesiologist's scope of practice also involves in-hospital and pre-hospital emergencies, work within intensive care units, acute pain units, and chronic pain consultations.

Patient-informed consent

Patient-informed consent is a medical principle stating that patients should be fully informed about the manner in which anesthesia will be administered to them. It is a fundamental ethical and legal principle and is considered essential for the patient autonomy. The American Society of Anesthesiologists and the American Osteopathic Board of Anesthesiology support this principle. In Germany, the law requires that prior to anesthesia, informed consent of the patient must be obtained by the anesthetist.

Due to medications given before, during, and after a surgery, a patient may sometimes not remember interactions with the anesthetist, involved in his anesthesia care. The anesthetic plan, as well as alternatives, risks, and benefits of the chosen anesthetic techniques, should be discussed with the patient prior to the surgery. This can be difficult or impossible in some situations, such as with unconscious patients, confused patients, or extremely urgent cases.

Selection and training

Selection and training process is similar in various countries.

Argentina

In Argentina, anesthetists are physicians who have specialized in the medical field of anesthesia. A Residency program is 5 years long.

Australia and New Zealand

In Australia and New Zealand, anesthetists are medical practitioners (with a university degree such as MB ChB or MB BS) who have undertaken specialist training in the medical field of anesthesia. They are represented by the Australian Society of Anaesthetists and the New Zealand Society of Anaesthetists.

Training is supervised by the Australian and New Zealand College of Anaesthetists. The ANZCA-approved training course encompasses an initial two-year long Pre-vocational Medical Education and Training (PMET) and three years of advanced training. Thus the total training is 5 years long. In the course, trainees are required to successfully complete five years of supervised clinical training at approved training sites and pass both the primary and final examinations which consist of both written (multiple choice questions and short-answer questions) and, if successful in the written exams, oral examinations (viva voce).

In the final written examination, there are many questions of clinical scenarios (including interpretation of radiological exams, EKGs and other special investigations). There are also two cases of real patients with complex medical conditions - for clinical examination and the following discussion. The course has a program of 12 modules such as obstetric anesthesia, pediatric anesthesia, cardiothoracic and vascular anesthesia, neurosurgical anesthesia and pain management. Trainees also have to complete an advanced project, such as a research publication or paper. They also undergo an EMAC (Effective Management of Anaesthetic Crises) or EMST (Early Management of Severe Trauma) course. On completion of training, the trainees are awarded the Diploma of Fellowship and are entitled to use the qualification of FANZCA – Fellow of the Australian and New Zealand College of Anaesthetists.

Brazil

In Brazil, the anesthetists are physicians who have specialized in the field of anesthesia. Approximately 650 physicians are admitted yearly to a three-year specialization program. The residency programs can take place at training centres in university hospitals. These training centres are accredited by the Brazilian Society of Anaesthesiology (SBA), or other referral hospitals accredited by the ministry of health. Most of the residents are trained in different areas, including ICU, pain management, and anesthesia sub-specialties, including transplants and pediatrics. In order to be a certified anesthetist in Brazil, the residents must give exams throughout the residency program and at the end of the program. The SBA conducts these examinations. In order to be an instructor of a residency program certified by the SBA, the anesthetists must have the superior title in anesthesia, in which the specialist undergoes a multiple choice test followed by an oral examination conducted by a board assigned by the national society.

Canada

In Canada, anesthesiologists are physicians (with the degree MD - Medicinae Doctorem or DO - Doctor of Osteopathic Medicine, or MDCM - Medicinae Doctorem et Chirurgiae Magistrum) who have specialized in the medical field of anesthesiology. Training is supervised by 17 universities approved by the Royal College of Physicians and Surgeons of Canada.^[1] Upon completion of a residency program (typically five year long), the candidate is required to pass a comprehensive objective examination consisting of a written component (two three-hour papers: one featuring 'multiple choice' questions, and the other featuring 'short-answer' questions) and an oral component (a two-hour session relating to topics on the clinical aspects of Anesthesiology). The examination of a patient is not required. Upon completion of training, the anesthesia graduate is then entitled to become a "Fellow of the Royal College of Physicians of Canada" and to use the post-nominal letters "FRCPC".

Canadian family physicians with one year of anesthesia training may also provide anesthetic services, but this is typically limited to smaller rural and remote hospitals. These physicians are often referred to as "GP anesthetists" or GPAs; alternatively they may be referred to as having a "2+1 in anesthesia" given their two years of family medicine residency and one year of anesthesia training. Technically, it would be incorrect to call a GPA an "anesthesiologist" as this term is exclusive to those having completed a five year anesthesiology residency, whereas the term "anesthetist" applies to anyone administering anesthesia to a patient.

Germany

In Germany, anesthetists (German: Anästhesist or Facharzt für Anästhesiologie) are the only anesthesia providers as German law does not allow anyone but a physician (doctor) to practice medicine. It is called a "physician-centred medicine" (German: Arztvorbehalt).

After earning the right to practice medicine (German: Approbation),^[2] German physicians who want to become anesthetists must undergo 5 years of training, consisting of anesthesia, ECG and pulmonary function testing, critical care and pain medicine, and also palliative care medicine. The training includes rotations serving in the operation theatres to perform anaesthesia on a variety of patients being treated by various surgical sub-specialties (e.g. general surgery, neurosurgery, invasive urological and gynecological procedures), followed by a rotation through various intensive-care units.^[3] Many German anaesthetists choose to complete a curriculum in emergency medicine, which once completed, enables them to be referred to as Notarzt, an emergency physician working pre-clinically with the emergency medical service. In pre-clinical settings the emergency physician is assisted by paramedics.^[4]

Netherlands

In the Netherlands, anesthetists are physicians who have specialized in the medical field of anesthesia. Anesthetists in the Netherlands must complete medical school training, which takes six years. After successfully completing medical school training, they start a five-year residency training in anesthesia. In their fifth year, they can choose to spend the year doing research or to specialize in a certain area, including regular anesthesia, critical care medicine, pain and palliative medicine, pediatric anesthesia, cardiothoracic anesthesia, neuro-anaesthesia or obstetric anesthesia.

Guatemala

In Guatemala, anesthetists are physicians who have specialized in the medical field of anesthesia. For this, a student with a medical degree (he or she must have surgery and general medicine skills by law) has to complete a residency of six years (five years in residency and one year of practice with an expert anesthetist).

After residency, students take a board examination conducted by the college of medicine of Guatemala, the Universidade De San Carlos De Guatemala (Medicine Faculty Examination Board), and a chief physician who represents the health care ministry of the government of Guatemala. The examination includes a written section, an oral section, and a special examination of skills and knowledge relating to anesthetic instruments, emergency treatment, pre-operative care, post-operative care, intensive care units, and pain medicine. After passing the examination, the college of medicine of Guatemala, Universidad De San Carlos De Guatemala and the health care ministry of the government of Guatemala grants the candidate a special license to practice anaesthesia as well as a diploma issued by the Universidad De San Carlos De Guatemala granting the degree of physician with specialization in anaesthesia. Anesthetists in Guatemala are also subject to yearly examinations and mandatory participation in yearly seminars on the latest developments in anesthetic practice.

Hong Kong

In Hong Kong, anesthesiologists are physicians who have specialized in the medical field of anesthesiology. To be qualified as an anesthesiologist in Hong Kong, medical practitioners must undergo a minimum of six years of postgraduate training and pass three professional examinations. Upon completion of training, the Fellowship of Hong Kong College of Anesthesiologists and subsequently the Fellowship of Hong Kong Academy of Medicine is awarded. Practicing anesthesiologists are required to register in the Specialist register of the Medical Council of Hong Kong and hence are under the regulation of the Medical Council. ^[5]

Italy

In Italy, the term anesthesiologist-intensive care doctor refers to a physician who, after completion of 6.5 years of medical school training, has completed an accredited four (five since 2008) year residency in anesthesiology. Such doctors work in operation theatres, ICUs, PACUs, Pain control units, Hyperbaric units, Emergency rooms, etc.

The Nordic Countries

In Denmark, Finland, Iceland, Norway, and Sweden, anesthesiologists' training is supervised by the respective national societies of anesthesiology as well as the Scandinavian Society of Anesthesiology and Intensive Care Medicine (SSAI). In the Nordic countries, anesthesiology is the medical specialty that is engaged in the fields of anesthesia, intensive care medicine, pain control medicine, pre-hospital and in-hospital emergency medicine. Anesthesiologist in the Nordics is a doctor who has completed a six-year undergraduate training program (from medical school), a twelve-month internship, and a five-year residency program. SSAI currently hosts five training programs for anesthesiologists in the Nordics. These are Intensive care, Pediatric anesthesiology and intensive care, Advanced pain medicine, Critical care medicine, and Advanced obstetric anesthesiology.

United Kingdom

In England, Northern Ireland, Scotland, and Wales, training is supervised by the Royal College of Anaesthetists. Anesthetists in the United Kingdom are physicians who have completed either a five-year or six-year undergraduate medical school training program or a four-year medical school program open only for postgraduates.

Following the completion of medical school training, physicians enter a two-year foundation program which consists of at least six, four-month rotations in various medical specialties. It is mandatory for all physicians to complete a minimum of three months of general medicine and general surgery training during this time. Following the foundation program, physicians compete for specialist training. The training program in the United Kingdom currently consists of two years of core training and five years of higher training. Also, before the end of core training, all trainees must have passed the primary examination for the diploma of Fellowship of the Royal College of Anaesthetists (FRCA).

Trainees wishing to hold dual accreditation in anesthesia and intensive care medicine may enter anesthesia training via the Acute Care Common Stem (ACCS) program which lasts three years and consists of experience in anesthesia, emergency medicine, acute medicine and intensive care. Trainees in anesthesia are called Specialty Registrars (StR) or Specialist Registrars (SpR). The Certificate of Completion of Training(CCT) in anesthesia is divided into three levels: Basic, intermediate and advanced. During this time, physicians learn anesthesia as applicable to all surgical specialties. The curriculum focuses on a modular format, with trainees primarily working in one special area during one module, for example, cardiac anesthesia, neuro-anaesthesia, ENT, maxillofacial, pain medicine, intensive care, and trauma. Traditionally (before the advent of the foundation program), trainees entered anesthesia from other specialties, such as medicine or accidents and emergencies. Specialist training takes at least seven years. On completion of specialist training, physicians are awarded CCT and are eligible for entry on the GMC Specialist register and are also able to work as consultant anesthetist. A new consultant in anesthetics must have completed a minimum of 14 years of training (including five to six years of medical school training, two years of foundation training, and seven years of anesthesia training).

Those wishing for dual accreditation (in Intensive care and anesthesia) are required to undergo an additional year of training and also complete the Diploma in Intensive Care Medicine (DICM). Pain specialists give the Fellowship of the Faculty of Pain Medicine of the Royal College of Anaesthetists (FFPMRCA) examination.

United States

Photo of prebriefing for mixed modality simulation being used for anesthesia resident training

In the United States, anesthesiologists are physicians (MD or DO) who have chosen to specialize in anesthesiology and are extensively trained. Anesthesiologists in the United States must have completed a four-year undergraduate college program (that includes pre-medical requirements) and four years of medical school training. Anesthesiology residency programs in the United States require successful completion of four years of residency training at an approved program for board certification eligibility in the specialty of anesthesiology.^[6] Anesthesiology residents face multiple examinations during their residency, including exams encompassing physiology, pathophysiology, pharmacology, and other medical sciences addressed in medical school, along with multiple anesthesia knowledge tests which assess progress during residency. Successful completion of a written and oral board exam after completion of residency is required for board certification.

Anesthesiology residency training in the U.S. encompasses the full scope of perioperative medicine, including pre-operative medical evaluation, management of pre-existing disease in the surgical patient, intraoperative life support, intraoperative pain control, post-operative recovery, intensive care medicine, and chronic and acute pain management. After residency, many anesthesiologists complete an additional fellowship year of sub-specialty training in areas such as pain management, sleep medicine, cardiothoracic anesthesiology, pediatric anesthesiology, neuroanesthesiology, regional anesthesiology/ambulatory anesthesiology, obstetric anesthesiology, or critical care medicine.^[7]

The average salary for a full-time anesthesiologists is roughly $470,000 according to US News.^[8] The number of jobs are rounding to about 170,400 according to statistics in 2014.^[9]

The majority of anesthesiologists in the United States are board-certified, either by the American Board of Anesthesiology (ABA) or the American Osteopathic Board of Anesthesiology (AOBA). D.O. anesthesiologists can be certified by the ABA. The ABA is a member of the American Board of Medical Specialties, while the AOBA falls under the American Osteopathic Association. Both Boards are recognized by the major insurance underwriters in the U.S. as well as by all branches of the U.S. Uniformed Services. Board certification by the ABA involves both a written and an oral examination. AOBA certification requires the same exams, in addition to a practical examination with examining physicians observing the applicant actually administering anesthetics in the operating room.

Propofol

From Wikipedia, the free encyclopedia

Propofol

Clinical data
AHFS/Drugs.com	Monograph
Pregnancy category	AU: C US: B (No risk in non-human studies)
Dependence liability	Physical: very low (seizures) Psychological: no data
Addiction liability	Moderate[1]
Routes of administration	Intravenous
ATC code	N01AX10 (WHO)
Legal status
Legal status	AU: S4 (Prescription only) CA: ℞-only UK: POM (Prescription only) US: ℞-only In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability	NA
Protein binding	95–99%
Metabolism	Liver glucuronidation
Onset of action	15–30 seconds[2]
Elimination half-life	1.5–31 hours[2]
Duration of action	~5–10 minutes[2]
Excretion	Liver
Identifiers
IUPAC name[show]
CAS Number	2078-54-8
PubChem CID	4943
IUPHAR/BPS	5464
DrugBank	DB00818
ChemSpider	4774
UNII	YI7VU623SF
KEGG	D00549
ChEBI	CHEBI:44915
ChEMBL	CHEMBL526
ECHA InfoCard	100.016.551
Chemical and physical data
Formula	C12H18O
Molar mass	178.271 g/mol
3D model (JSmol)	Interactive image

Propofol, marketed as Diprivan among others, is a short-acting medication that results in a decreased level of consciousness and lack of memory for events. Its uses include the starting and maintenance of general anesthesia, sedation for mechanically ventilated adults, and procedural sedation. It is also used for status epilepticus if other medications have not worked. It is given by injection into a vein. Maximum effect takes about two minutes to occur and it typically lasts five to ten minutes.

Common side effects include an irregular heart rate, low blood pressure, burning sensation at the site of injection, and the stopping of breathing.^[2] Other serious side effects may include seizures, infections with improper use, addiction, and propofol infusion syndrome with long-term use.^[2] It appears to be safe for using during pregnancy but has not been well studied in this group.^[2] However, it is not recommended during cesarean section.^[2] Propofol is not a pain medication, so opioids such as morphine may also be used.^[3] Whether or not they are always needed is unclear.^[4] Propofol is believed to work at least partly via a receptor for GABA.^[2]

Propofol was discovered in 1977 and approved for use in the United States in 1989.^[2][5] It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.^[6] It is available as a generic medication.^[2] The wholesale price in the developing world is between 0.61 and 8.50 USD per vial.^[7] It has been referred to as milk of amnesia (a play on milk of magnesia) because of the milk-like appearance of the intravenous preparation.^[8][9] Propofol is also used in veterinary medicine.^[10]

Medical uses

Anesthesia

Propofol is used for induction and maintenance (in some cases) of general anesthesia, having largely replaced sodium thiopental.^[3] It can also be administered as part of an anaesthesia maintenance technique called total intravenous anesthesia using either manually-programmed infusion pumps or computer-controlled infusion pumps in a process called target controlled infusion or TCI. Propofol is also used to sedate individuals who are receiving mechanical ventilation but are not undergoing surgery, such as patients in the intensive care unit. In critically ill patients, propofol has been found to be superior to lorazepam both in effectiveness and overall cost.^[11]

Propofol is often used instead of sodium thiopental for starting anesthesia because recovery from propofol is more rapid and "clear."

Procedural sedation

Propofol is also used for procedural sedation. Its use in these settings results in a faster recovery compared to midazolam.^[12] It can also be combined with opioids or benzodiazepines.^[13][14][15] Because of its fast induction and recovery time, propofol is also widely used for sedation of infants and children undergoing MRI.^[16] It is also often used in combination with ketamine as the two together have lower rates of side effects.^[17]

Other uses

Executions

The Missouri Supreme Court decided to allow the use of propofol to execute prisoners condemned to death. However, the first execution by administration of a lethal dose of propofol was halted on 11 October 2013 by governor Jay Nixon following threats from the European Union to limit the drug's export if it were used for that purpose.^[18][19] The United Kingdom had already banned the export of medicines or veterinary medicines containing propofol to the United States.^[20]

Recreational use

Recreational use of the drug via self-administration has been reported,^[21][22] but is relatively rare due to its potency and the level of monitoring required for safe use.^{[citation needed]} Critically, a steep dose-response curve makes recreational use of propofol very dangerous, and deaths from self-administration continue to be reported.^[23][24] The short-term effects sought via recreational use include mild euphoria, hallucinations, and disinhibition.^[25][26]

Recreational use of the drug has been described among medical staff, such as anesthetists who have access to the drug,^[27][28] and is reportedly more common among anesthetists on rotations with short rest periods (as rousing is to a well-rested state).^[29] Long-term use has been reported to result in addiction.^[27][30]

Attention to the risks of off-label use of propofol increased in August 2009 due to the Los Angeles County coroner's conclusion that music icon Michael Jackson died from a mixture of propofol and the benzodiazepine drugs lorazepam, midazolam and diazepam on June 25, 2009.^{[31][32][33][34]} According to a 22 July 2009 search warrant affidavit unsealed by the district court of Harris County, Texas, Jackson's personal physician, Conrad Murray, administered 25 milligrams of propofol diluted with lidocaine shortly before Jackson's death.^[32][33][35] Even so, as of 2016 propofol was not on a U.S Drug Enforcement Administration schedule.^[29][36]

Side effects

One of propofol's most frequent side effects is pain on injection, especially in smaller veins. This pain arises from activation of the pain receptor, TRPA1,^[37] found on sensory nerves and can be mitigated by pretreatment with lidocaine.^[38] Less pain is experienced when infused at a slower rate in a large vein (antecubital fossa). Patients show great variability in their response to propofol, at times showing profound sedation with small doses.

Additional side effects include low blood pressure related to vasodilation, transient apnea following induction doses, and cerebrovascular effects. Propofol has more pronounced hemodynamic effects relative to many intravenous anesthetic agents.^[39] Reports of blood pressure drops of 30% or more are thought to be at least partially due to inhibition of sympathetic nerve activity.^[40] This effect is related to dose and rate of propofol administration. It may also be potentiated by opioid analgesics.^[41] Propofol can also cause decreased systemic vascular resistance, myocardial blood flow, and oxygen consumption, possibly through direct vasodilation.^[42] There are also reports that it may cause green discolouration of the urine.^[43]

As a respiratory depressant, propofol frequently produces apnea. The persistence of apnea can depend on factors such as premedication, dose administered, and rate of administration, and may sometimes persist for longer than 60 seconds.^[44] Possibly as the result of depression of the central inspiratory drive, propofol may produce significant decreases in respiratory rate, minute volume, tidal volume, mean inspiratory flow rate, and functional residual capacity.^[39]

Diminishing cerebral blood flow, cerebral metabolic oxygen consumption, and intracranial pressure are also characteristics of propofol administration.^[45] In addition, propofol may decrease intraocular pressure by as much as 50% in patients with normal intraocular pressure.^[46]

A more serious but rare side effect is dystonia.^[47] Mild myoclonic movements are common, as with other intravenous hypnotic agents. Propofol appears to be safe for use in porphyria, and has not been known to trigger malignant hyperpyrexia.^{[citation needed]}

Propofol is also reported to induce priapism in some individuals,^[48][49] and has been observed to suppress REM sleep stage and to worsen the poor sleep quality in some patients.^[50]

As with any other general anesthetic agent, propofol should be administered only where appropriately trained staff and facilities for monitoring are available, as well as proper airway management, a supply of supplemental oxygen, artificial ventilation, and cardiovascular resuscitation.^[51]

Propofol infusion syndrome

Another recently described rare, but serious, side effect is propofol infusion syndrome. This potentially lethal metabolic derangement has been reported in critically ill patients after a prolonged infusion of high-dose substance in combination with catecholamines and/or corticosteroids.^[52]

CBS genetic defects

People with this gene have trouble processing sulphites (one of the potential ingredients).

Interactions

The respiratory effects of propofol are increased if given with other respiratory depressants, including benzodiazepines.^[53]

Mechanism of action

Propofol has been proposed to have several mechanisms of action,^[54][55][56] both through potentiation of GABA_A receptor activity and therefore acting as a GABA_A receptor positive allosteric modulator, thereby slowing the channel-closing time, and at high doses, propofol may be able to activate GABA_A receptors in the absence of GABA, behaving as a GABA_A receptor agonist as well. ^[57][58][59]. Propofol analogs have been shown to also act as sodium channel blockers.^[60][61] Some research has also suggested that the endocannabinoid system may contribute significantly to propofol's anesthetic action and to its unique properties.^[62] EEG research upon those undergoing general anesthesia with propofol finds that it causes a prominent reduction in the brain's information integration capacity at gamma wave band frequencies.^[63]

Researchers have identified the site where propofol binds to GABA_A receptors in the brain, on the second transmembrane domain of the beta subunit of the GABA_A receptor.^[64]

Pharmacokinetics

Propofol is highly protein-bound in vivo and is metabolised by conjugation in the liver.^[65] The half-life of elimination of propofol has been estimated to be between 2 and 24 hours. However, its duration of clinical effect is much shorter, because propofol is rapidly distributed into peripheral tissues. When used for IV sedation, a single dose of propofol typically wears off within minutes. Propofol is versatile; the drug can be given for short or prolonged sedation, as well as for general anesthesia. Its use is not associated with nausea as is often seen with opioid medications. These characteristics of rapid onset and recovery along with its amnestic effects^[66] have led to its widespread use for sedation and anesthesia.

Chemistry

A 20-ml ampoule of 1% propofol emulsion, as sold in Australia by Sandoz

Propofol was originally developed in the UK by Imperial Chemical Industries as ICI 35868. Clinical trials followed in 1977, using a form solubilised in cremophor EL. However, due to anaphylactic reactions to cremophor, this formulation was withdrawn from the market and subsequently reformulated as an emulsion of a soya oil/propofol mixture in water. The emulsified formulation was relaunched in 1986 by ICI (now AstraZeneca) under the brand name Diprivan. The currently available preparation is 1% propofol, 10% soybean oil, and 1.2% purified egg phospholipid as an emulsifier, with 2.25% glycerol as a tonicity-adjusting agent, and sodium hydroxide to adjust the pH. Diprivan contains EDTA, a common chelation agent, that also acts alone (bacteriostatically against some bacteria) and synergistically with some other antimicrobial agents. Newer generic formulations contain sodium metabisulfite or benzyl alcohol as antimicrobial agents. Propofol emulsion is a highly opaque white fluid due to the scattering of light from the tiny (about 150-nm) oil droplets it contains.

A water-soluble prodrug form, fospropofol, has recently been developed and tested with positive results. Fospropofol is rapidly broken down by the enzyme alkaline phosphatase to form propofol. Marketed as Lusedra, this new formulation may not produce the pain at injection site that often occurs with the traditional form of the drug. The US Food and Drug Administration approved the product in 2008.^[67] However fospropofol is a Schedule IV controlled substance with the DEA ACSCN of 2138 in the United States unlike propofol.^[68]

Recent developments

By incorporation of an azobenzene unit, a photoswitchable version of propofol (AP2) was developed in 2012 that allows for optical control of GABA_A receptors with light.^[69] In 2013, a propofol binding site on mammalian GABA_A receptors has been identified by photolabeling using a Diazirine derivative.^[70] Additionally, it was shown that the hyaluronan polymer present in the synovia can be protected from free-radical synovia by propofol.^[71]

Propofol is one of the chemicals used in the manufacture of the investigational drug avasimibe.

The Transhuman Singularity

 March 27, 2001 by Terry Grossman
Original link:  http://www.kurzweilai.net/the-transhuman-singularity

Therapeutic human cloning, stem cell therapies, synthetic organs, molecular nanotechnology, and the digital-cerebral interface may allow us to achieve immortality in this century. But keeping bionic transhumans alive until immortalilty is achieved may prove very expensive. And not everyone will want it.

At 54 years of age, I am among the oldest of the baby boomers. Many of us, belonging to this and subsequent generations, don’t really believe that we will have to die. Death for us, if and when it occurs, will simply be the result of some kind of awful mistake.

In accordance with my predictions for the near future, with a little luck, my generation of boomers may be the first ever to be presented with the option for physical immortality on Earth. For members of all younger generations, this may almost be guaranteed. It may even be a possibility, albeit only sporadically, for a number of today’s seniors as well.

But, as a group, people who are less than 55 or so right now have the best chance of still being alive when the widespread availability of physical immortality becomes a reality. Experts predict that this dramatic extension in human lifespan will debut between 25 and 50 years from now¹.

There is, needless to say, considerable controversy over the exact date that extreme human longevity will become widely available. Ron Klatz MD, president of The American Academy of Anti-Aging Medicine, suggests that the human life span will reach 150 years within 30 years and physical immortality will be achieved by mid-century. Other futurists feel such dramatic breakthroughs may take a little longer.² Ray Kurzweil even goes so far as to states that “life expectancy (will) no longer be a viable term in relation to intelligent beings” sometime between 2072 and 2099.³

This dramatic increase in human longevity will be the result of a number of imminent scientific breakthroughs. In my recent book, The Baby Boomers’ Guide to Living Forever4, I discuss these concepts at further length and present a plan of action that can be taken by anyone (not just baby boomers, by the way!) to improve your chances of remaining alive long enough to experience these soon-to-be-available radical increases in human longevity.

In The Baby Boomers’ Guide to Living Forever , I begin my discussion of how to plan for extreme longevity with “The Three Rules of Living Forever.”

• Rule #1: Don’t die anytime soon.
• Rule #2: Stay away from most doctors.
• Rule #3: Follow “The Ten Pillars of Health.”

In The Ten Pillars of Health I discuss specifically what types of things you can start doing right now to increase your chances of living a longer and healthier life. You can go to the website associated with this book, where brief descriptions of each of The Ten Pillars of Health are presented.

Defining the Singularity

Vernor Vinge popularized the concept of The Singularity–the point in time when machines become more intelligent than humans–in his essay, “The Technological Singularity.”

I use the phrase here differently, to refer to the point in time when human beings cross over the line and become immortal. Vernor Vinge popularized this version of The Singularity in his science fiction novel Marooned in Real Time.

I feel that this singular event corresponding to the end of death’s icy grip on human life will be among the most spectacular of triumphs for Life itself. This day that Death dies will join together with the day that Life took its first breath as the two most important dates in the history of life on our planet.

Not everyone feels this way about this. The majority of people now alive, in fact, have never even thought of this and even if they have, pay it little mind. This is because most people today feel that they are immortal already. They believe that they are already guaranteed life eternal as a result of their religious beliefs. The majority of Americans believe that their souls are immortal. As the reality of The Singularity approaches, however, the frequency and intensity of the debate regarding the relative merits of physical vs. ethereal immortality is certain to increase.

It will be interesting to see in which direction people are drawn when they really do have a clear-cut choice in the matter:

• Stay here on earth on the physical plane with their current memories intact or
• Die and then take their chances on getting in to heaven, the Happy Hunting Grounds, nirvana, Valhalla, etc.

The question comes to mind as to whether only “good” people will choose heaven, figuring that they have the best chance of getting in there. The sinners among us, on the other hand, would be more likely opt for staying right here on earth as long as possible rather than risk their summary deportation to the eternal flames of “the other place.” Will this dichotomy serve as a form of natural selection and eventually lead to an increasingly unsavory populace increasingly comprised of criminals and other borderline types immortalized “down” here?

This decision making process of choosing between heavenly bliss (or the Happy Hunting Grounds, nirvana, Valhalla, etc.) or continuing with the “rat race” here on earth will not be a trivial matter either. The version of physical immortality that I foresee, wonderful though it is to me, will not be everyone’s cup of tea.

Achieving this type of personal immortality will necessitate the use of therapeutics some people currently regard as dangerous (e.g., genetic engineering), other therapies that are currently illegal (e.g., human cloning) and still others that don’t even exist yet (e.g., human consciousness “uploading”). In the eyes of some folks, these interventions are totally unacceptable or even blasphemous. To others the type of “life” available to us will be an abomination and we won’t even meet the definition of being human any more. If history is any guide, a certain subgroup of our fellows will devote their lives to seeing that these options are not available to anyone.

The progression from where we are now, deeply mired in the quicksand of mortality, to the arrival of The Singularity will be characterized by a number of discrete quantum leaps that will be necessary to take us from where we are today to where we will need to be.

Some of the most notable of these biotechnological advances that will bring us to level where true human immortality will be possible include:

• Therapeutic Human Cloning
• Pluripotent Stem Cell Therapies
• Synthetic Human Organs
• Molecular Nanotechnology
• Creation of the “Digital-Cerebral Interface”

Therapeutic human cloning refers to the creation of human organs directly from an individual’s own DNA. It is currently legal, unlike “human cloning,” in which case an individual is duplicated in toto to create an entirely new genetically identical being.

Stem cells are specialized cells in the body that have the ability to turn into any of a number of diverse cell types. A particular type of these cells, the pluripotent stem cells, exist for just the first few weeks of embryonic development, but have the unique ability to turn into any cell type in the body whatsoever. These cells can also be used to create human replacement parts.

Another way to duplicate human replacement organs is in the factory. Engineers are working to fabricate entirely synthetic or artificial human organs and tissues. The availability of permanent artificial hearts, for example, is anticipated by 2010 followed in short order by synthetic, implantable lungs and kidneys by 2015. Predictions include the widespread availability of synthetic brains by 2035.⁵

Molecular nanotechnology (MNT) refers to engineering on a very tiny scale. Above all other technologies, MNT has the potential to irrevocably alter Life-As-We-Know-It by creating almost any product we desire from its raw materials at negligible cost. Infinitesimally tiny nanotechnological robots (nanobots) may some day circulate throughout our brains, systematically creating a digital record of the position of each molecule, providing a backup copy of our memories.

In accordance with Kurzweil’s “Law of Accelerating Returns,”⁶ these advances will bring about ever more rapid changes in human Life-As-We-Know-It. A large part of these changes will be the result of the exponential increase in the computing power surrounding us. We will move from where we are today, increasingly dependent on external computers that help us conduct our business and access information, to the next level where computers gradually become part of us.

From the desktop, laptop and palmtop computers of today, we will soon progress to “belt tops” and then to non-visible computers implanted within our bodies. Within the next few decades, as suggested above, implanted computers will help our brains to think, while doctors also begin to implant organic as well as synthetic organs to replace worn out or diseased body parts.

This gradual change from carbon-based organic human beings into “transhumans” consisting of more than 50% bionic and/ or machine parts will be the next step in human evolution. The most notable feature of this evolutionary quantum leap will be our transformation from creatures of flesh and bone to being mostly machine-made, from being humans to becoming transhumans.7

It will be interesting to see the psychological changes that will occur to transhumans during this transitional period as people begin to grapple with the prospects for living an essentially indefinite period. In addition, as more and more people come to realize that they have a serious chance at immortality if they only survive for a few more years, our healthcare system will come under even greater pressure to keep people alive. Economic factors will play an ever-increasing role.

Keeping people alive as transhumans may prove very expensive. As more and more people look to keep themselves alive at whatever cost so that they will still around for The Singularity, more and more organs will need to be repaired, replaced or regrown. This could get very expensive indeed. The economic issues involved, as well as a number of others, will ensure that transhumanism won’t last very long at all.

From transhumanism, where we are partly organic tissue and partly mechanical parts, the natural progression will be toward greater and greater dependence on ever more rapid computer-augmented thinking and consciousness. Simultaneously, our relationship with our physical bodies will become increasingly evanescent. We may choose to continue to spend part of our time as physical beings, but many of us may find further evolution into posthuman existence, where we exist as purely energetic beings far more to our liking.

In addition to allowing for much more rapid assimilation and processing of information, such existence will also be far less expensive than constantly repairing physical bodies. On a philosophical level, the dividing line between heaven and earth, or, perhaps between human existence and nirvana, will begin to disappear.

The ramifications of this quantum leap in evolution to an entirely novel state of being, to posthumanism, are gargantuan. Will we mere mortals of today ever be able to adapt to such an existence? Or will we, like the children of Israel many centuries ago, just wander about for another 40 years or so, yet be allowed no more than a glimpse of The Promised Land?

The children of Israel were forced into Brownian marching in the Sinai Desert just long enough to ensure that all among them who had been slaves in Egypt died off first. Will it be the same story for today’s mortal humans? Having been born into lives of slavery under the yoke of mortality, perhaps we just can’t be trusted in a world where there is no death. The powers that be may already know that this would be too much of a shock to our psyches. It’s the ultimate caste system. You are either born an immortal or you’re not. No one gets to change.

As a true digital-cerebral interface comes into existence and we are able to “upload” our memories and consciousness into a twin computer backup, true human immortality will follow automatically as a matter of course. This creation of a twin consciousness of self on the digital plane will be the defining moment of The Singularity. For as soon as this is done, and we are able to create backup copies of ourselves, by definition, we’re immortal.

Should we want to, and I am not sure how many of us will even want to bother, this computer replication of self may then be downloaded into a newly cloned body (a 25 year old version, of course) and the process repeated indefinitely— Eternal Youth and True Physical Immortality.

The Singularity, therefore, refers to human immortality, the chance to live in a physical body (or virtually if you prefer, of course) for as long as you want. And, I repeat, current estimates are that this option should be available sometime during the present century.

Conceptions About Death

I think that people who lived in previous times may have felt the same way— that they would never die either— at least they may have thought this when they were young. Young people don’t usually spend a lot of time thinking about their own mortality. Have you ever met a teenager who didn’t think of himself or herself as indestructible and immortal?

Yet, with the passage of time, things begin to change. The years take their toll, and these young people, now middle aged, see this one and that one around them beginning to make the baleful passage from this world. The idea that they too will die one day gradually seeps into their consciousness. Right now the inflection point, the age at which the transition occurs— before which you think that you will never die and after which you know that it is only a matter of time— roughly corresponds to the age of today’s baby boomers.

Many who are younger than this age group still believe that they will never die— or at least they don’t think about death very often. On the other side, for people over 55 years of age or so, the thought patterns change. Very often, for instance, I ask some of my older patients, mostly retirees and other senior citizens, how long they expect to live or how long they might want to live if they had a choice in the matter.

Interestingly, very few of them ever show the remotest interest in immortality or even in a dramatic increase in life expectancy. Their expectations have been shaped by their perceptions. “What they see is what they get.” They see many people their own age dying, so they feel it is only a matter of time for them as well.

In addition, many of them have already been stricken with the infirmities and disabilities that aging has wrought. As a result, they lack enthusiasm for continuing in their current condition, not to speak of what they anticipate would inevitably be an even worse condition, for a whole lot longer. Most of them lack the vision of their children and grandchildren to conceive of a future where your physical health actually gets better and you appear to grow younger with the passage of time.

Yet, when the rubber hits the road, it has also been my experience that the age to which many elderly people aspire keeps moving farther and farther away the closer they get to what they think might be their actual “endpoint.” My impression is that even the oldest of the old almost always want to live a little longer. As Dr. Ron Klatz, founder of the American Academy of Anti-Aging Medicine has said, “if you are wondering why anyone would want to live to be 120, anyway, just ask someone who’s 119.”

Most seniors don’t really want to die, they just think they have to. So, they spend much of their energy getting ready. If you are a senior, I recommend that you consider spending at least as much time preparing for your possible immortality as you do making preparations for your death.

Individuals a little younger, however, have yet to suffer many of the more serious slings and arrows of that outrageous process commonly referred to as aging. The lightning bolts have still begun to strike us only sporadically. For young and not-so-young adults, the worst symptom of aging reported by even the most senior of us is the receipt of unsolicited literature urging us to join AARP. Senior citizen discounts at the movies remain, mercifully, a few years away. A not so occasional ache and pain here and there, some thinning or graying hair, and a few creases on the forehead or crow’s feet around the eyes are the worst age related indignities suffered by this group.

This change in the way we view life itself with an increasing belief in the prospect for immortality will represent a huge paradigm shift in societal thought. The possible outcomes of that shift are staggering. Will we become uncontrollable risk takers with no thoughts of the consequences of our actions because we have no fear of death? Or fearing nothing, will we also care about nothing? Then again we may care more … about the long-term health of the planet, for example, because we’ll be sticking around so much longer. We may care more about one another since we’ll be with one another so much longer, etc. What about the economy? And politics? What about education? So many unknowns lie ahead.

In the course of a lifetime measured in centuries, it could become common to have several marriages, many careers, recurring courses of higher education. Will economic status play a role in who gets to live forever and who doesn’t, or will we truly have a world of “Forever for All”? The whole social structure will change, and Life-As-We-Know-It will change utterly.

Life Needs to be Fun

Still, no matter how long we live, for it to make any difference at all, life needs to be fun. Death and taxes, at least according to Benjamin Franklin, are the only certainties in life. I am not so sure of either of these certainties anymore. Some of my friends tell me they have no intention of dying–while others pay virtually no taxes.

Personally, I am more intrigued with the idea of dodging the Grim Reaper than the tax collector at this stage in my life. Should the concepts presented forthwith prove successful, then I suppose it would be fun to look at this other “inevitability” of life, paying taxes, and see if this, too, can be simply avoided.

A key concept here is that life needs to be fun. For my own part, I am more intrigued with the idea of living forever than with the reality. I like the challenge. Presented with the option of life everlasting, I don’t know exactly how I would handle it. There are only so many types of ethnic restaurants one wants to try. Yet, as it is often said, it still beats the alternative.

But it really isn’t necessary that we live forever anyway, we simply need to believe that we can. Having faith that one will never die, a concept well known to religious faithful worldwide, can take a lot of the wind out of Death’s dark sails. I think that the main precondition for human happiness is simply being having the belief that we will still be alive tomorrow. As long as we have faith that tomorrow will be here for us, whatever is going on today is a lot easier to take.

In the words of George Bernard Shaw— “There are two tragedies in life. One is to lose your heart’s desire. The other is to gain it.” Perhaps life needs to be a struggle, and wrestling with mortality is the Mother of All Struggles. By taking death out of the equation, a lot of the struggle disappears. But, if life needs to be a struggle, life will be a struggle, if by no other means than our making it be so.

Immortality for All

Furthermore, I don’t believe there is anything sacrilegious about my position, although I know there are many who might disagree with me. Between the concepts presented here regarding physical immortality and the unpopular notions espoused by former governor of Colorado Richard Lamm in the distant 1970s that the “elderly have a duty to die” lies a wide spectrum of viewpoints. There are countless ideas about how long any of us should live or should even have the right to live.

Some people say that manipulating the human lifespan is an attempt to tinker with nature and that avoiding death is unnatural, running counter to the natural scheme of things. These people contend that humans have no business tinkering with something as inviolate as death. I completely disagree, and, to help clarify my reasoning, I wish to ask a few questions of them.

How do they feel about the use of antibiotics to treat a case of pneumonia, which would otherwise prove fatal? Doesn’t this also violate the natural order of things and, thus, should also be forbidden? Well, these critics argue, you’re still alive when you take the antibiotics.

Then, what about the use of a defibrillator to restore an absent heartbeat following a heart attack? In this case, they respond, it’s only a “near death experience,” during which the patient is not really dead, just “near-dead” briefly, for a few minutes or less.

How about someone who has suffered “near drowning”? Resuscitation efforts are often successful even if a person has been “drowned” for several hours. During this period in the water, the victim is usually cold, without either heartbeat or consciousness. That’s pretty much dead in my book. Yet they often are restored to life and appear completely normal.

The bottom line is that humans have been tinkering with the natural order of things from before the days of the Neanderthals. Tinkering is what we do. We tinker with the natural order of things. I don’t believe The Greater Power has any problem with our doing so, either. I don’t believe The GP is in any great rush for us to join Him/Her. The Greater Power has been around for a long time, and is going to be around for a long time more. Whether any of us spend a few more years or a few more centuries “down” here or “up” here, as the case may be, doesn’t make the slightest difference in that time frame.

A meek accountant, who was also a very religious man, prayed long and hard that The Greater Power would appear to him. One day, his prayers were answered.

“What can I do for you?” asked The Greater Power.

“I can’t believe that You would take the time to visit me, a meek accountant. Compared to You, I am just a speck of dust, while You are so great and powerful,” said the accountant.

“That’s right,” said The Greater Power.

“And a million dollars to You is just like a penny to me.”

“You’re right there, too. A million dollars is just like a penny to Me.”

“And a million years to You is just like a minute to me,” said the accountant.

“Right again, a million years is just like a minute.”

“Well, Greater Power,” asked the accountant, “do You think You might be able to lend me a few pennies?”

“Of course, my child,” boomed the answer, “just wait a minute.”

On the contrary, I think The-Greater-Powers-That-Be totally support our efforts. The priority of all living beings is to ensure the continuance of life. Anything we can do to sustain life is in keeping with the true natural order of things. We wouldn’t have been given the brains and the imagination we possess if we weren’t meant to use them.

So, here we stand at the gateway of a new millennium, with the light of The Singularity already a faint glimmer on a distant horizon. What a truly wonderful time to be alive! What an amazing series of challenges lie ahead for humankind along with a remarkable series of opportunities. In closing, I wish want to express my most fervent desire that each of us be granted the basic immortality wish: simply to be given the gift of one more day … every day.

1. Klatz, Ronald. Grow Young with HGH, New York: HarperCollins, 1997, pp. 313-314 and “Making The Quantum Leap to Human Immortality in the Year 2029,” Anti-Aging Medical News, pp. 1-12.

2. Even by the most conservative estimates, human life spans of 150 years are predicted by 2050 and of 200 years or more by 2100. (See The Wall Street Journal, 10/18/99, p. B-8.)

3. Kurzweil, Ray. The Age of Spiritual Machines, New York: Penguin Books, 1999, p. 280.

4. Grossman, Terry. The Baby Boomers’ Guide to Living Forever, Hubristic Press: Denver CO, 2000.

5. Klatz, Ronald. Anti-Aging Medical News, Fall, 2000, pp. 8-12.

6. Kurzweil, Ray, op cit, 29-30.