Intubation only

(oxygenation and ventilation are adequate but the patient needs a secure airway)
Threatened airways obstruction;e.g., deep coma
Definite airways obstruction;e.g., laryngeal edema, tracheal tumor

Either indication must be based solely on the clinical examination, although arterial blood gas measurement is often helpful to assure that mechanical ventilation is not necessary.


Intubation and mechanical ventilation
(oxygenation and/or ventilation are not adequate)

*Apnea

*Impaired alveolar ventilation (as assessed by PaCO2) when accompanied by one or more of the following:
a. Depressed mental status
b. Increasing fatigue
c. Reduced PaO2 that cannot otherwise be corrected
d. Severely deranged pH that cannot otherwise be corrected
e. Compromise of upper airways (e.g., by secretions)

*Low PaO2 (e.g., less than 60 mm Hg): a. that cannot be improved with an FIO2 less than 0.50, and b. that is causing symptoms or seriously impairing bodily function

Degradation of CO₂ Absorbers:

Degradation of CO₂ absorbers (barolime or soda lime) produces Compound A (pentafluroisopropenyl fluromethylether). It is not a metabolism product, but degradation. This is unique to sevoflurane. Compound A and fluoride are both nephrotoxic in rats, and quite possibly humans at large quantities. A wide variety of patients have been exposed to both sevofluorane and compound A and their kidney function did not change. Compound A forms glutathione conjugates in the liver, mediated by beta lyase of the Cytochrome P-450 microsomal superfamily of isozymes. This is an enzyme in the kidney. The nephrotoxicity was found during research on rats, where the beta lyase works 10X better than in humans, so compound A’s degradation product sevofluorane doesn’t seem to be a problem in humans even though it showed that result in rats.

Local and Regional Anesthetics

There are two classes of local’s. They are either amides or esters. Every local has both a hydrophobic and hydrophilic part. The hydrophobic part is generally a ring structure and the hydrophilic is generally an acid. Between the two is either the amide or ester bond. When you are asked to distinguish an amide from an ester, you just need to look at the nomenclature. All locals are –caine’s. On the generic name of the drug, if there’s the letter “I” anywhere in the name before “-caine,” it’s an amide. Let’s practice: lidocaine = amide. Bupivicaine = amide, cocaine = ester, procaine = ester, (xylocaine) = amide because (xylocaine) is a brand name; (xylocaine) is the brand name for lidocaine.

Locals are often mixed with other agents like preservatives, or epinephrine for vasoconstriction. Locals given alone are called plain, and those given with epi are called a local anesthetic with epinephrine. You must be careful when using epi. Epi will aid the anesthetic by increasing its duration of action because locals are generally weakened by diffusion, but epi will hold the drug in place longer because of its vasoconstricting capabilities. Epi is generally used because it will make the drug last longer and decrease bleeding (which can be both a + because it will decrease bleeding around a wound, and a – because you may not recognize any “bleeders” before you tie off the incision, causing a hematoma under the skin later when the epi wears off.) A negative aspect of epi is if it is used in terminal circulation like fingers, toes, ear cartilage, nose you may cut off the only circulation to the area. Although true allergies are extremely rare many patients will claim to be allergic to “novocaine” (which contrary to many med student’s beliefs is not used anymore) but they are just uncomfortable when feeling the natural effects of epinephrine, so make sure you ask your patients what symptoms they experience when they were given the local anesthetic.

Locals tend to be toxic. 2% lidocaine is 20mg/mL. If the toxicity for lidocaine is 5-7 mg per Kg body weight of patient (70 kg patient needs about 350 - 490 mg of lidocaine to be toxic, that’s 17.5 - 24.5 mL of 2% lidocaine or 10 – 14.5 carpules for all you mathematically challenged), you must be careful how much is given, because depending on how quickly it diffuses throughout the body, some major damage can be done. Like other drugs, locals have varying levels of diffusion and pharmacology. However, toxicity and duration of action go hand in hand with locals. Drugs that are short acting are generally nontoxic. Nessicaine and chlorprocaine can be given very rapidly but because it is “broken up so quickly we can’t even give enough of it to create toxicity.” Longer acting drugs can produce toxicity. Bupivicaine is not even given in ¾% strength anymore because there were too many problems with toxicity.

Toxicity for locals involve CNS and the heart. The major problem for these generally arise when they are accidentally given in the wrong location. For example, when an epidural is given but the needle is putting anesthetic into the epidural vein. To prevent this a test dose is given to make sure the dose is given into the epidural space. Using an epidural as our example, to make sure that the injection is being placed in the correct location, a small injection is given in the epidural space. If the patient says they have a feeling of impending doom, that their heart is racing, they don’t think they’re breathing right (even though they generally are), the test dose was given into the epidural vein. This is fine, because the response lasts about 20 seconds, while adjustments are made in the site of injection. A second test dose can then be given, and after no response, the anesthetic is given. This actually happens kind of frequently.

Poisons This also explains how Locals work:

Tetrodotoxin (TTX) and saxotoxin. They generally occur in Japanese puffer fish. They block Na channels, inhibiting axonal conduction. They are two of the most potent poisons known. The duration of action of these NMJ blockers are similar to anesthetics, except that their mechanism of action is for days to weeks. If someone eats puffer fish that is not properly prepared, they can be ventilated with hemodynamic support for a week or two until the poison is metabolized. Locals are much quicker in action by comparison so they can be given therapeutically when not given systemically.

Pre-anesthetic considerations:

Sometimes drugs are given before anesthesia is given. There are conditions that must be considered, like anxiety, so a sedative such as valium, which also causes anterograde amnesia another desired effect, can be given. Some drugs are given as prophylaxis to suppress some potential adverse responses to general anesthesia, or to minimize secretions (not so common anymore), to prevent bradycardia, or to minimize aspiration. Some of these substances, such as sodium citrate, are given to increase stomach pH so that if someone did aspirate, they wouldn’t aspirate such acidic material. Drugs are sometimes given for postoperative nausea. An antiemetic can be given pre-op or during the surgery to minimize problems. Some examples are:

1. Benzodiazepines are used for amnesia.

2. Barbiturates or narcotics are used as sedatives to relieve anxiety.

3. Anti-cholinergics are used to reduce secretions and prevent bradycardia.

(Note: these are being used before anesthesia)

Intraoperative Anesthesia:

5 components used during anesthesia, (with drugs that best carry out that function next to it):

1) Amnesia -- Benzodiazepines

2. Analgesia -- narcotics

3. Anesthesia – barbiturates (sodium pentathal), amidazols (atomidate), phencyclidine (ketamine), phenolic compounds like propofol (diprivan)

4. Muscle relaxation – neuromuscular blocking agents

5. Hemodynamic stability

1)Benzodiazepines given IV can work as anesthetic. It can also be used as an antiseizure med, along with being a great amnestic, and good sedative.These drugs include diazepam (Valium), midazolam (Versed).and narcotics s as well, all with some effect on BP. Depending on the patient, you choose a drug that best suits your needs for the patient.

2) Narcotics classically bind opioid receptors. Morphine is the classical example. They are agonists to opioid receptors. There are several classes of opioid receptors, being mu1, mu2, kappa, delta, and sigma. Depending on relative binding, you may see variations in respiration depression, analgesia, nausea, vomiting, and other side effects associated with opioids.

Meperidine (Demerol), fentanyl, sufentanil, alfentanil, and remifentanil are all opioids. Remifentanil is a short acting opioid. The mainstays are still morphine and fentanyl. Sufentanil is newer. 100 mg of (Demerol) = 10 mg morphine. 10 mg of morphine = 100 g of fentanyl = 10 g sufentanil. As a narcotic agonist, fentanyl is about 10 times more potent than morphine. Sufentanil is probably about 100 times more potent than morphine.

While morphine induces histamine release, and affect blood pressure, these newer drugs are cardio-stable. Patients on cardiac anesthetic procedures probably have a narcotic like fentanyl or sufentanil. Respiratory function is not as important in these patients because we’re breathing for them with respirators

3) Barbiturates The newer drugs generally bring a patient rapidly to a level 3 or 4, because they essentially stop breathing, this is not a problem because when we use positive pressure on ventilation.

Examples include sodium thiopental and methohexital (brevital). They are rapid acting intravenous agents causing significant respiratory (and sometimes cardiac) depression. Sodium pentathal is unique in that it does not cause seizures. It raises seizure threshold. Methohexital will decrease seizure threshold. For these reasons, in a patient with status epilepticus or if there is a need to intubate a patient who is seizing, sodium pentathal is used.

All barbiturates are a derivative of barbituric acid, which is a 5 carbon ring structure. Depending on the orientation of the side groups, you can have thiobarbiturates (with sulfur containing), or oxybarbiturates, like methohexital

Neuromuscular blocking agents do not promote any sense of euphoria or well being or any other functions besides complete paralysis. They must be used in conjunction with drugs that cause amnesia or you will have a patient awake and paralyzed on the table.

4) Neuromuscular Blocking Agents. They’re also known as muscle relaxants, but that’s misleading because they cause paralysis. These aren’t the drugs you would receive if you went to see your family doc for back pain and he or she gave you something that made you drowsy and you wake up with your back feeling better. These drugs do not alter level of consciousness or perception of pain. You must support or control ventilation when using these drugs and monitor the anesthetic level because the patient can be lying there in pain and awake, just paralyzed (I personally ask that this be done to me when I’m undergoing surgery because I like to feel every cut of the knife.)They interrupt nerve impulses at the neuromuscular junction (NMJ).

Succinylcholine is the one depolarizing agent used. It causes a randomized firing of muscle fibrils before causing paralysis. Patients receiving succinylcholine may have fasciculations when they first receive the med.

Nondepolarizing agents go straight to flaccid (don’t you just love this word) paralysis. You will not see fasciculations. They are all basically curare type drugs. They differ slightly by onset of action, pharmacology, duration of action and the way in which they’re metabolized. There are two groups of nondepolarizers.

One group is like pancuronium. Pancuronium is an older drug that is still used that is steroid based. Vecuronium is also a steroid class drug. As an aside, Dr. Vitkun informed us that D-Cuvocurarium is the poisoned arrow drug that was used by aborigine’s to kill prey. They’d shoot an animal and chase it until it dropped from the poison causing paralysis.

Atracurium is a bis-isoquinolonium derivative. They have a very different type of metabolism. A newer drug called cis-atracurium undergoes Hoffman elimination, meaning that elimination is solely temperature and pH dependent. Therefore, this is the drug of choice for the patient in liver or kidney failure, or both. Dr. Vitkun then reminded us that inhaled anesthetics also do not need the kidneys or liver, as they are exhaled for elimination. Even though there is some metabolism, because of the time course, the majority of elimination is through exhalation.

5) Phencyclidines Ketamine, also known at parties as special K, is a very good amnestic and analgesic. It is a dissociative anesthetic agent. It maintains respiration. You can give an induction dose and maintain blood pressure and respiration to a large extent. It is termed a dissociative anesthetic and produces a fugue state, meaning that it separates mind from body (alright now were talking). These effects can occur because phencyclidines are more commonly known as PCP or “angel dust,” thereby facilitating those effects. Because of its near relatives, ketamine has now become a controlled drug in NY. It is also known as the “date rape drug.” It has veterinary use. Interestingly, animals are LESS sensitive to ketamine than us weakly humans. This is probably in relation to how it works in the brain. It is a good drug for trauma and for asthmatics.

Negatives are the abuse potential and “emergence delirium.” “Emergence delirium” is the “medicalized” term for a “bad trip” akin to that experienced from PCP. It is in 10 – 15% of patients under Ketamine.

These drugs are used for the induction of anesthesia. Ketamine was most commonly used in children. They’re also used in trauma and burn patients to maintain blood pressure and respiration because they’re generally hemodynamically stable.

Flow rates on anesthetics are measured in liters. The amount of flow makes a difference not just the percent of each is administered. The advantages to giving a 2L flow over a 4L flow are:

1. The amount of air that will remain in your system – air that will be “rebreathed” – will remain higher.

2. You will be breathing a warmer gas. It will conserve energy or heat for you.

3. There will be less being scavenged out of the system. Less gas will be wasted.

4. It’s cheaper.

5. The air is more humidified.

The disadvantage to a 2L administration flow are:

Components of anesthesia – Amnesia, analgesia, relaxation.

Types of anesthesia

• General – Describes a loss of sensory perception over the entire body. Requires the use of many different agents (narcotics, inhalation agents, muscle relaxants).

• Regional – Describes a loss of sensory perception over a specific part of the body (spinal, epidural, axillary, ankle block). Local anesthetics are used.

• Local – Describes a loss of sensory perception over a very small area of the body. Local anesthetics are used.

• 
  

Phases of anesthesia – Induction (putting someone to sleep), maintenance, emergence.

Rules for differentiating amides and esters – Amides have an “i” before “-caine.”

MOA of local anesthetics – Block nerve conduction reversibly by blocking Na+ channels, which prevents depolarization and propagation of nerve impulses.

Conduction blocking factors

• Lipid solubility – Determines anesthetic potency.

• Degree of protein binding – Determines duration of action.

• pKa – All anesthetics are weakly basic with pKa of about 8. Anesthetics can be manipulated by adding small amounts of bicarbonate at the time of administration. This drives the anesthetic toward the non-ionized form. The more non-ionized the anesthetic, the greater the diffusion across the membrane, which speeds the rate of onset.

Anesthetic use with epinephrine – Allows greater duration of anesthetic effect. Can lead to hypoxic necrosis in areas with reduced blood flow.

Complications

• Traumatic injury to nerves

• Infection

• Bleeding

• Tissue neurotoxic reactions

• Hypoxic brain damage

• Allergic reactions – To some amino esters due to release of PABA.

• Systemic toxic reactions

New safer anesthetics – Compared with bupivicaine. Ropivicaine is structurally similar but doesn’t have the toxic effects (removed R enantiomer). Levo-bupivicaine has the bad stuff separated out.

Neuromuscular blockade – Muscle relaxants are necessary to facilitate intubation, provide muscle relaxation during surgery, and facilitate artificial ventilation. They act on two different cholinergic receptors: muscarinic and nicotinc.

Classes of muscle relaxants – Non-depolarizers and depolarizers (succinycholine)

• Non depolarizers – Competitive inhibitors of acetylcholine at the receptor. Virtually all have “cur” in their names (cis-atricuronium & rapidcuronium). To reverse the blocking effects of these drugs, one must administer an acetylcholinesterase inhibitor such as neostigmine or edrophonium. Additionally, with the increase in acetylcholine that results from use of inhibitor, you will get increased muscarinic effects such as bradycardia and the potential for asystole, so one must give an anti-muscarinic such as atropine or glycopyrolate (preferred because it does not cross BBB).

• Depolarizers – Bind to the receptor and cause fasciculations and then sit there for 5-10 minutes. Succinylcholine (metabolized by plasma pseudocholinesterase) is the only on used clinically but has numerous side effects:

  • Fasciculations – Prevent by giving a small dose of nondepolarizer (defasciculating dose).

  • Malignant hyperthermia – Treat with dantrolene.

  
  

Twitch monitor – Usually goes on ulnar nerve. The twitch monitor will NOT tell you how fully recovered the patient is. Train of Four – if no twitches, 95% or more of receptors are blocked; 1 of 4, 90% blockade; 2 of 4, 80%, 3 of 4, 75%; 4 of 4, 65%. The best it can tell you is that there are 2/3 of receptors still blocked. That is why the twitch monitor is used intraoperatively but not for signs of recovery.

Signs of recovery – Lift head up and hand grip (33% receptor block). Clinical signs are important.

Muscle relaxants – You don’t have to use them to intubate, but it makes things easier. Used to facilitate intubation and induction. Used to promote ideal conditions. Effects are monitored with an electric nerve stimulator and by observing clinical signs.

Stages and signs of general anesthesia – Stage I (analgesia); stage II (delirium); stage III (surgical anesthesia); stage 4 (medullary paralysis).

Bispectral index monitor – Measures the relative degree of anesthesia to prevent light anesthesia. Processed EEG (100 is wide awake). Signs of light anesthesia include body movement, increased heart rate and BP.

Inhalation anesthetics – Characteristics are controllability and non-specificity.

Factors that determine uptake of a volatile anesthetic – CO, solubility, uptake = [lambdaQ(Pa-Pv)]/barometric pressure. Lambda is the blood:gas coefficient and is directly related to solubility

Potency – Measured by the minimum alveolar concentration (MAC). MAC of 1 is the concentration at which there is a 50% response to painful stimuli. MAC of 1.3 is the dose at which 100% of patients will not move. Supplement general anesthetic with NO unless contraindicated because NO has less effect on cardiac and pulmonary systems than inhalation agents.

Factors affecting MAC – Older age and pregnancy DECREASE MAC; alcohol abuse INCREASES MAC.

Side effects of inhalation agents – Increases respiratory rate, decreases tidal volume in a dose-dependent matter, overall a slight respiratory depression with a slight decrease in carbon dioxide.

• Halothane – Nonflammable, as are all agents developed in the last 40 yrs; halothane hepatitis associated with repeated anesthesia, hypoxia, and female patients and due to reductive metabolism (which liberates fluoride); all can causes malignant hyperthermia (dantrolene is DOC for treatment of malignant hyperthermia); not used much anymore.

• Isoflurane – Pungent, potent, and nonflammable; much better recovery profile than halothane (15 minutes); used for outpatient procedures; recently replaced by desflurane and sevoflurane.

• Desflurane – Shortest recovery period so very useful in outpatient setting.

• Sevoflurane – Now used in place of halothane in pediatric inductions (better profile).

• Nitrous oxide – Only gas used to aid in general anesthesia.

IV anesthesia – Desirable characteristics include rapid onset, short duration, high clearance, minimal side effects, cost effectiveness, residual analgesia, and rapid recovery

Barbituates

• Thiopental sodium – Potent, ultra short-acting, works in 5-10 sec; side effects include depression of circulation and ventilation; highly lipid soluble.

• Methohexital

Non-barbituates

• Etomidate – Imidazole; minimal cardiorespiratory depression; excellent for elderly patients and asthmatics (no histamine release).

• Propofol – White milky substance; causes quicker emergence than barbs; heavily used in outpatient setting.

Note: Both barbs and non-barbs have no analgesic properties and no muscle-relaxing properties in normal doses.

Ketamine – PCP derivative; rich analgesic effects; increases heart rate and blood pressure (good for trauma patient); can produce nightmares.

Benzodiazepines – Far safer than barbs but strong potential for addiction; used as pre-anesthetic medications to reduce anxiety and produce some amnesia; no significant cardiorespiratory depression; NO analgesic properties either; work at GABA receptors in the amygdala, hippocampus, and prefrontal cortex; causes hyperpolarization thru opening of Cl- channels.

• Diazepam (Valium) – Lasts 20-40 hrs; half-life is 1 hr per age of patient once over 60 yrs old; very addictive; very few depressive effects.

• Lorazepam (Adavan) – Half-life of 10-20 hrs;

• Midazolam (Verced) – Good preoperative drug.

• Flumazenil – BENZODIAZEPINE RECEPTOR ANTAGONIST used to reverse effects of benzos; fast-acting and very selective.

Narcotics – Often given as a supplement to volatile anesthetics and contribute to the MAC. All narcotics cause a dose-dependent respiratory depression.

• Fentanyl – 100x more potent than morphine; minimal cardiac depression; must be given IV; works for 90 min; no histamine release.

• Sulfentanyl – 1000x more potent than morphine; no histamine release.

• Meperidine (Demerol) – Atropine-like structure; 1/10 as potent as morphine; rarely used due to interaction with MAO inhibitors (LETHAL).

Novel agents

• Remifentanil

• Toradol – NSAID that is nearly as potent as morphine; no respiratory depression; affects bleeding profile.

• Ondansetron – Potent anti-emteic used for chemo patients and in the OR with nausea-associated narcotics and general anesthetics; 5-HT subtype 3 antagonist.