HOW DO ANESTHETICS WORK?

the anesthesia consultant

Physician anesthesiologist at Stanford at Associated Anesthesiologists Medical Group
Richard Novak, MD is a Stanford physician board-certified in anesthesiology and internal medicine.Dr. Novak is an Adjunct Clinical Professor in the Department of Anesthesiology, Perioperative and Pain Medicine at Stanford University, the Medical Director at Waverley Surgery Center in Palo Alto, California, and a member of the Associated Anesthesiologists Medical Group in Palo Alto, California.
email rjnov@yahoo.com
phone 650-465-5997

I commonly hear two questions from my patients: “How does anesthesia work?” and “How do the anesthetic drugs make me fall asleep?”

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The short answer to both questions is, “We’re not sure.”

This column is designed as a brief tutorial for non-anesthesiologists who wish to better comprehend how anesthetic drugs work.

General anesthesia is the sum of hypnosis (sleep), amnesia, analgesia (pain relief), and the lack of any motion response to pain. Propofol and barbiturates cause hypnosis. Versed and other benzodiazepines cause amnesia. Narcotics such as morphine and fentanyl cause analgesia. Paralyzing drugs such as rocuronium, vecuronium and succinylcholine cause muscle relaxation and lack of motion.

The potent inhaled anesthetics sevoflurane, desflurane, and isoflurane produce all four of the effects of hypnosis, amnesia, analgesia, and lack of motion.

The molecules of anesthetic drugs have great diversity. Some are very small, such as nitrous oxide, while others such as propofol or barbiturates have complex formulas. Some are gases and some are injected liquids. This diversity leads investigators to postulate that there are multiple mechanisms of action for anesthetic drugs on the brain.

Drugs such as propofol and Versed are injected into the bloodstream and are circulated to the central nervous system, where they carry out their effect on brain cells. Inhaled anesthetics such as sevoflurane and desflurane traverse from the lungs into the bloodstream and are circulated to the central nervous system, where they carry out their effect on brain cells.

Once in the brain, it’s not clear how anesthetic drugs work. Most anesthetic drugs are hydrophobic, which literally translates to “water fearing.” This means their molecules are more soluble in fat than in water. Anesthetic drugs exhibit a correlation between their potency and how hydrophobic they are. The entry of any drug into a brain cell must be via the outer lining, or membrane, of that cell. Investigators believe anesthetics must move through, or bind to, the fat-soluble aspects of the membranes of brain cells. The drugs likely then bind to proteins within the cell membranes, and cause their anesthetic effect by changing the characteristics of ion channels within the cell membranes. There is no unifying theory as to how this occurs, but it is known that anesthetic agents have effects on brain cell membrane proteins, which depend on the hydrophobic, electrostatic, and size properties of the individual drug.

Specific examples in our understanding of anesthetic actions include:

(1) Barbiturate drugs, propofol, and inhalational anesthetics are known to act by potentiating a brain chemical called gamma-aminobutyric acid, or GABA. GABA is an inhibitory neurotransmitter, meaning it’s a brain chemical which inhibits other brain activity. This inhibition in some way promotes unconsciousness.

(2) The anesthetics nitrous oxide and ketamine are known to antagonize an excitatory Nmethyl-d-aspartate (NMDA) subtype of neurotransmitter. By blunting this excitatory process, the drugs work to promote unconsciousness.

The takeaway message is that no specific premise exists to explain how all the different general anesthetic drugs work on the brain. A variety of mechanisms likely results in similar effects on the brain, each eliminating the transmission of sensory messages to the brain and initiating unconsciousness.

Anesthesiologists administer other types of drugs, including narcotics, paralyzing drugs, and local anesthetics. The mechanisms of action of these medications are better understood.

fentanyl

Narcotics such as morphine, fentanyl, Demerol, or Dilaudid cause pain relief by binding to opioid receptors in the brain (or the spinal cord). The most common narcotic side effects, e.g. sleepiness and nausea, also arise from the direct effect of the narcotics on the brain. Narcotics bind to three specific receptors in the central nervous system: the mu, delta, and kappa receptors. The mu receptor is primarily responsible for the pain-relieving and euphoria-inducing effects of narcotics. Investigators are searching for new narcotics to specifically target the mu receptor, with the aim of reducing side effects of sedation and nausea.

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Muscle relaxants (muscle paralyzing drugs) such as rocuronium, vecuronium, and succinylcholine act on the body’s peripheral skeletal muscles. Muscles normally contract when a neurotransmitter molecule named acetylcholine travels from a nerve ending and binds to a receptor on the neuromuscular junction on the muscle. This binding causes the muscle to contract. Succinylcholine paralyzes muscles by binding to and activating the acetylcholine receptor, first by causing a muscle contraction and then by rendering the muscle flaccid. Rocuronium and vecuronium paralyze muscles by competitively binding to the receptor and blocking the normal access of acetylcholine, which renders the muscle flaccid.

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Local anesthetic drugs such as lidocaine, bupivicaine (Marcaine), and ropivicaine temporarily block the function of nerves outside the central nervous system. These local anesthetic drugs block the peripheral nerve from conducting of the feeling of pain to the brain. Nerve conduction is dependent on the opening of sodium channels in nerve cell membranes, allowing an influx of sodium ions into the nerve. The blocking of sodium transport renders the nerve incapable of transmitting the pain message.

Modern anesthetic care can involve all the drugs discussed above. For example, in a general anesthetic for an abdominal surgery, the anesthesiologist may inject Versed into the IV as a premedication to reduce anxiety, then inject propofol into the IV to initiate sleep, and inject rocuronium into the IV to induce muscle relaxation/paralysis prior to inserting an endotracheal breathing tube. General anesthesia is then maintained by the administration of a potent inhaled anesthetic gas such as sevoflurane, supplemented by the intravenous injection of a narcotic such as fentanyl to assure post-operative pain relief.

Physician anesthesiologists must master the diverse anesthetic drug repertoire of injectable hypnotics, narcotics, muscle relaxants, as well as the inhaled general anesthetics. The selection of the proper anesthetic drugs and doses for each individual patient makes anesthesiology both fun and fascinating.

Reference:  Mantilla CB, Wong GY, Molecular and cellular mechanisms of anesthesia, Faust’s Anesthesiology Review, Elsevier, 2013, Chapter 60, 139-41.

 

The most popular posts for laypeople on The Anesthesia Consultant include:

How Long Will It Take To Wake Up From General Anesthesia?

Why Did Take Me So Long To Wake From General Anesthesia?

Will I Have a Breathing Tube During Anesthesia?

What Are the Common Anesthesia Medications?

How Safe is Anesthesia in the 21st Century?

Will I Be Nauseated After General Anesthesia?

What Are the Anesthesia Risks For Children?

 

The most popular posts for anesthesia professionals on The Anesthesia Consultant  include:

10 Trends for the Future of Anesthesia

Should You Cancel Anesthesia for a Potassium Level of 3.6?

12 Important Things to Know as You Near the End of Your Anesthesia Training

Should You Cancel Surgery For a Blood Pressure = 178/108?

Advice For Passing the Anesthesia Oral Board Exams

What Personal Characteristics are Necessary to Become a Successful Anesthesiologist?

 

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Published in September 2017:  The second edition of THE DOCTOR AND MR. DYLAN, Dr. Novak’s debut novel, a medical-legal mystery which blends the science and practice of anesthesiology with unforgettable characters, a page-turning plot, and the legacy of Nobel Prize winner Bob Dylan.

KIRKUS REVIEW

In this debut thriller, tragedies strike an anesthesiologist as he tries to start a new life with his son.

Dr. Nico Antone, an anesthesiologist at Stanford University, is married to Alexandra, a high-powered real estate agent obsessed with money. Their son, Johnny, an 11th-grader with immense potential, struggles to get the grades he’ll need to attend an Ivy League college. After a screaming match with Alexandra, Nico moves himself and Johnny from Palo Alto, California, to his frozen childhood home of Hibbing, Minnesota. The move should help Johnny improve his grades and thus seem more attractive to universities, but Nico loves the freedom from his wife, too. Hibbing also happens to be the hometown of music icon Bob Dylan. Joining the hospital staff, Nico runs afoul of a grouchy nurse anesthetist calling himself Bobby Dylan, who plays Dylan songs twice a week in a bar called Heaven’s Door. As Nico and Johnny settle in, their lives turn around; they even start dating the gorgeous mother/daughter pair of Lena and Echo Johnson. However, when Johnny accidentally impregnates Echo, the lives of the Hibbing transplants start to implode. In true page-turner fashion, first-time novelist Novak gets started by killing soulless Alexandra, which accelerates the downfall of his underdog protagonist now accused of murder. Dialogue is pitch-perfect, and the insults hurled between Nico and his wife are as hilarious as they are hurtful: “Are you my husband, Nico? Or my dependent?” The author’s medical expertise proves central to the plot, and there are a few grisly moments, as when “dark blood percolated” from a patient’s nostrils “like coffee grounds.” Bob Dylan details add quirkiness to what might otherwise be a chilly revenge tale; we’re told, for instance, that Dylan taught “every singer with a less-than-perfect voice…how to sneer and twist off syllables.” Courtroom scenes toward the end crackle with energy, though one scene involving a snowmobile ties up a certain plot thread too neatly. By the end, Nico has rolled with a great many punches.

Nuanced characterization and crafty details help this debut soar.

Click on the image below to reach the Amazon link to The Doctor and Mr. Dylan:

41wlRoWITkL

LEARN MORE ABOUT RICK NOVAK’S FICTION WRITING AT RICK NOVAK.COM BY CLICKING ON THE PICTURE BELOW:

DSC04882_edited

 

 

HOW TO WAKE UP PATIENTS PROMPTLY FOLLOWING GENERAL ANESTHETICS

the anesthesia consultant

Physician anesthesiologist at Stanford at Associated Anesthesiologists Medical Group
Richard Novak, MD is a Stanford physician board-certified in anesthesiology and internal medicine.Dr. Novak is an Adjunct Clinical Professor in the Department of Anesthesiology, Perioperative and Pain Medicine at Stanford University, the Medical Director at Waverley Surgery Center in Palo Alto, California, and a member of the Associated Anesthesiologists Medical Group in Palo Alto, California.
email rjnov@yahoo.com
phone 650-465-5997

Two patients arrive simultaneously in the recovery room following general endotracheal anesthetics. One patient is unresponsive and requires an oral airway to maintain adequate respiration. In the next bed, the second patient is awake, comfortable and conversant. How can this be? It occurs because different anesthetists practice differently. Some can wake up patients promptly, and some cannot.

 

Does it matter if a patient wakes up promptly after general anesthesia? It does. An awake, alert patient will have minimal airway or breathing problems. When it’s time to walk away from your patient in the recovery room, you’ll worry less if your patient is already talking to you and has minimal residual effects of general anesthesia. Whether the surgery was a radical neck dissection, a carotid endarterectomy, a laparotomy, or a facelift, it’s preferable to have your patient as awake as possible in the recovery room.

What can you do to assure your patients wake up promptly? A Pubmed search will give you little guidance. There’s a paucity of data or evidence in the medical literature on how to wake patients faster. You’ll find data on ultra-short acting drugs such as propofol and remifentanil. This data helps, but the skill of waking up a patient on demand is more an art than a science. Textbooks give you little advice. Anesthesiologist’s Manual of Surgical Procedures, (4th Edition, 2009), edited by Jaffe and Samuels, has an Appendix that lists Standard Adult Anesthetic Protocols, but there is little specific information on how to titrate the drugs to ensure a timely wakeup.

Based on 29 years of administering over 20,000 anesthetics, this is my advice on how to wake patients promptly from general anesthesia:

  1. Propofol. Use propofol for induction of anesthesia. You may or may not choose to infuse propofol during maintenance anesthesia (e.g. at a rate of 50 mcg/kg/min) but if you do, I recommend turning off the infusion at least 10 minutes before planned wakeup. This allows adequate time for the drug to redistribute and for serum propofol levels to decrease enough to avoid residual sleepiness.
  2. Sevoflurane. Sevoflurane is relatively insoluble and its effects wear off quickly when the drug is ventilated out of the lungs at the conclusion of surgery. I recommend a maintenance concentration of 1.5% inspired sevoflurane in most patients. I drop this concentration to 1% while the surgeon is applying the dressings. When the dressings are finished, I turn off the sevoflurane and continue ventilation to pump the sevoflurane out of the patient’s lungs and bloodstream. The expired concentration will usually drop to 0.2% within 5-10 minutes, a level at which most patients will open their eyes.
  3. Nitrous oxide. Unless there is a contraindication (e.g. laparoscopy or thoractomy) I recommend you use 50% nitrous oxide. It’s relatively insoluble, and adding nitrous oxide will permit you to utilize less sevoflurane. I recommend turning off nitrous oxide when the surgeon is applying the dressings at the end of the case, and turning the oxygen flow rate up to 10 liters/minute while maintaining ventilation to wash out the remaining nitrous oxide.
  4. Narcotics. Use narcotics sparingly and wisely. I see overzealous use of narcotics as a problem. Prior to inserting an endotracheal tube, it’s reasonable to administer 50 – 100 mcg of fentanyl to a healthy adult or 0 -50 mcg of fentanyl to a geriatric patient. A small dose serves to blunt the hemodynamic responses of tachycardia or hypertension associated with larynogoscopy and intubation. Bolusing 250 mcg of fentanyl prior to intubation is an unnecessary overdose. The use of ongoing doses of narcotics during an anesthetic depends on the amount of surgical stimulation and the anticipated amount of post-operative pain. You may administer intermittent increments of narcotic (I may give a 50-100 mcg dose of fentanyl every hour) but I recommend your final narcotic bolus be given no less than 30 minutes prior to the anticipated wakeup. Undesired high levels of narcotic at the conclusion of surgery contribute to oversedation and slow awakening. If your patient complains of pain at wakeup, further narcotic is titrated intravenously to control the pain. Your patient’s verbal responses are your best monitor regarding how much narcotic is needed. Your goal at wakeup should be to have adequate narcotic levels and effect, but no more narcotic than needed.
  5. Intra-tracheal lidocaine. I recommend spraying 4 ml of 4% lidocaine into the larynx and trachea at laryngoscopy prior to inserting the endotracheal tube. I can’t cite you any data, but it’s my impression that patients demonstrate less bucking on endotracheal tubes at awakening when lidocaine was sprayed into their tracheas. Less bucking enables you to decrease anesthetic levels further while the endotracheal tube is still in situ.
  6. Local anesthetics. Local anesthetics are your friends at the conclusion of surgery. If the surgeon is able to blunt post-operative pain with local anesthesia or if you are able to blunt post-operative pain with a neuroaxial block or a regional block, your patient will require zero or minimal intravenous narcotics, and your patient will wake up more quickly.
  7. Muscle relaxants. Use muscle relaxants sparingly. Nothing will slow a wakeup more than a patient in whom you cannot reverse the paralysis with a standard dose of neostigmine. This necessitates a delay in extubation until muscle strength returns. Muscle relaxation is necessary when you choose to insert an endotracheal tube at the beginning of an anesthetic, but many cases do not require paralysis for the duration of the surgery. When you must administer muscle relaxation throughout surgery, use a nerve stimulator and be careful not to abolish all twitch responses. Avoid long-acting paralyzing drugs such as pancuronium, as you will have difficulty reversing the paralysis if surgery concludes soon after you’ve administered a dose. Use rocuronium instead. Avoid administering a dose of rocuronium if you believe the surgery will conclude within the next 30 minutes—it may be difficult to reverse the paralysis, and this will delay wakeup.
  8. Laryngeal Mask Airway (LMA). When possible, substitute an LMA for an endotracheal tube. Wakeups will be smoother, muscle relaxants are unnecessary, and narcotic doses can be titrated with the aim of keeping the patient’s spontaneous respiratory rate between 15- 20 breaths per minute.
  9. Temperature monitoring and forced air warming. Cold is an anesthetic. Strive to keep your patient normothermic by using forced air warming. If your patient’s core temperature is low, wakeup will be delayed.

10. Consider remaining in the operating room after surgery until your patient is awake enough to respond to verbal commands. This is my practice, and I recommend it for safety reasons. In the operating room you have all your airway equipment, drugs, and suction at your fingertips. If an unexpected emergence event occurs, you’re prepared. If an unexpected emergence event occurs in an obtunded patient in the recovery room, your resuscitation equipment will not be as readily available. If your patient is responsive to verbal commands in the operating room, your patient will be wakeful on arrival in the recovery room.

Is this protocol a recipe? Yes, it is. You’ll have your own recipe, and your ingredients may vary from mine. You may choose to administer desflurane instead of sevoflurane. You may choose sufentanil, morphine, or meperidine instead of fentanyl. My advice still applies. Use as little narcotic as is necessary, and try not to administer intravenous narcotic during the last 30 minutes of surgery. If you use a remifentanil infusion, taper the infusion off early enough so the patient is wakeful at the conclusion of surgery.

The principles I’ve recommended here are time-tested and practical. Follow these guidelines and you’ll experience two heartwarming scenarios from time to time:  1) Patients in the recovery room will ask you, “You mean the surgery is done already? I can’t believe it,” and 2) Recovery room nurses will ask you, “Did this patient really have a general anesthetic?  She’s so awake!”

Your chest will swell with pride, and you’ll feel like an artist. Good luck.

 

 

The most popular posts for laypeople on The Anesthesia Consultant include:

How Long Will It Take To Wake Up From General Anesthesia?

Why Did Take Me So Long To Wake From General Anesthesia?

Will I Have a Breathing Tube During Anesthesia?

What Are the Common Anesthesia Medications?

How Safe is Anesthesia in the 21st Century?

Will I Be Nauseated After General Anesthesia?

What Are the Anesthesia Risks For Children?

 

The most popular posts for anesthesia professionals on The Anesthesia Consultant  include:

10 Trends for the Future of Anesthesia

Should You Cancel Anesthesia for a Potassium Level of 3.6?

12 Important Things to Know as You Near the End of Your Anesthesia Training

Should You Cancel Surgery For a Blood Pressure = 178/108?

Advice For Passing the Anesthesia Oral Board Exams

What Personal Characteristics are Necessary to Become a Successful Anesthesiologist?

 

 

 

 

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*
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*

Published in September 2017:  The second edition of THE DOCTOR AND MR. DYLAN, Dr. Novak’s debut novel, a medical-legal mystery which blends the science and practice of anesthesiology with unforgettable characters, a page-turning plot, and the legacy of Nobel Prize winner Bob Dylan.

KIRKUS REVIEW

In this debut thriller, tragedies strike an anesthesiologist as he tries to start a new life with his son.

Dr. Nico Antone, an anesthesiologist at Stanford University, is married to Alexandra, a high-powered real estate agent obsessed with money. Their son, Johnny, an 11th-grader with immense potential, struggles to get the grades he’ll need to attend an Ivy League college. After a screaming match with Alexandra, Nico moves himself and Johnny from Palo Alto, California, to his frozen childhood home of Hibbing, Minnesota. The move should help Johnny improve his grades and thus seem more attractive to universities, but Nico loves the freedom from his wife, too. Hibbing also happens to be the hometown of music icon Bob Dylan. Joining the hospital staff, Nico runs afoul of a grouchy nurse anesthetist calling himself Bobby Dylan, who plays Dylan songs twice a week in a bar called Heaven’s Door. As Nico and Johnny settle in, their lives turn around; they even start dating the gorgeous mother/daughter pair of Lena and Echo Johnson. However, when Johnny accidentally impregnates Echo, the lives of the Hibbing transplants start to implode. In true page-turner fashion, first-time novelist Novak gets started by killing soulless Alexandra, which accelerates the downfall of his underdog protagonist now accused of murder. Dialogue is pitch-perfect, and the insults hurled between Nico and his wife are as hilarious as they are hurtful: “Are you my husband, Nico? Or my dependent?” The author’s medical expertise proves central to the plot, and there are a few grisly moments, as when “dark blood percolated” from a patient’s nostrils “like coffee grounds.” Bob Dylan details add quirkiness to what might otherwise be a chilly revenge tale; we’re told, for instance, that Dylan taught “every singer with a less-than-perfect voice…how to sneer and twist off syllables.” Courtroom scenes toward the end crackle with energy, though one scene involving a snowmobile ties up a certain plot thread too neatly. By the end, Nico has rolled with a great many punches.

Nuanced characterization and crafty details help this debut soar.

Click on the image below to reach the Amazon link to The Doctor and Mr. Dylan:

41wlRoWITkL

 

LEARN MORE ABOUT RICK NOVAK’S FICTION WRITING AT RICK NOVAK.COM BY CLICKING ON THE PICTURE BELOW:

DSC04882_edited