Sedation & General Anesthesia
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STAGES OF ANESTHESIA
There are 4 (Guedel’s) stages of anesthesia. They are not distinct stages but a continuum of overlapping stages. Patients undergoing conscious sedation are prevented from reaching the second stage. Within the first stage there are four plateaus.
Stage I (stage of analgesia or disorientation): from induction of general anesthesia to loss of consciousness.
Four plateaus of Stage I anesthesia (analgesia):
- Paresthesia: tingling of hands, feet. Lightheadedness.
- Vasomotor: warm sensations.
- Drift: euphoria, pupils centrally fixed (no dilation), sensation of floating. The target plateau.
- Dream: eyes closed but will open in response to questions; difficulty in speaking; jaw sags open. This is where the dose would be adjusted to prevent drifting into stage II.
Stage II (stage of excitement or delirium): from loss of consciousness to onset of automatic breathing. The patient may move their limbs, hold breath, or become violent. Vomiting may occur. Blood pressure rises and pupil dilation seen, drooping eyelids. An anesthetist wants to pass through this stage quickly. In general anesthesia stage I and II are referred to as induction.
Stage III (stage of surgical anesthesia): from onset of automatic respiration to respiratory paralysis. It is divided into four planes.
Stage IV: from respiratory paralysis till death. Anesthetic overdose causes medullary paralysis.
A patient with an acute respiratory infection is a contraindication for general anesthesia.
NITROUS OXIDE
Conscious sedation falls under stage 1 anesthesia, when there is minimal suppression of the level of consciousness, the patient retains the ability to control their own airway and are able to respond to physical and verbal stimuli. Nitrous oxide is a gas commonly used in pediatric sedation. The purpose of nitrous oxide sedation is to reduce fear/apprehension/anxiety and fatigue, while raising the patient’s pain threshold. It has rapid onset and recovery because of the very low plasma solubility. Nitrous is easily titratable and generally lacks serious adverse effects.
Minimum alveolar concentration (MAC) is a measure of the potency, defined as the concentration required to produce immobility in 50% of the patients. The MAC for NO is 105%. A higher MAC value represents a less potent anesthetic. There is no biotransformation of the gas which is rapidly excreted by the lungs. Drugs with decreased blood solubility have rapid induction and rapid recovery. Drugs with increased lipid solubility have increased potency. A larger difference in partial pressure between alveolar gas and venous blood will increase uptake.
The blood–gas partition coefficient (or Ostwald coefficient for blood–gas) describes the solubility of inhaled general anesthetics in blood. It is the ratio of the concentration in blood (dissolved and undissolved) to the concentration in gas that is in contact with that blood, when the partial pressure between the two areas are equal. A higher blood-gas partition coefficient indicates a stronger affinity for plasma proteins (more soluble), slower onset and slower recovery. A lower coefficient like that of nitrous oxide (0.47) is preferable.
The total flow rate during the procedure is 4-6L/min (enough to keep the reservoir bag 1/3 to 2/3rds full), a mixture of oxygen (green tank) and nitrous oxide (blue tank). The proportion is increased in 10-20% increments until that patient reaches the drift plateau, the maintenance dose is usually around 30%. Oxygen should not drop below 30%, and the maximum dose of nitrous should not exceed 50%. Local anesthesia is still used since the gas only produces a little analgesia.
Nausea and vomiting is the most common side effect of nitrous oxide sedation. Vomiting can be dangerous if the patient is allowed to pass through to Stage II and starts to lose airway control. When the procedure is completed diffusion hypoxia can occur. The nitrous oxide is quick to push out of the tissues (high MAC) and can dilute the available oxygen in the lungs. For this reason patients are given 100% oxygen for 3-5 minutes following the procedure.
Prolonged exposure to nitrous oxide in a working environment can have negative health effects, including bone marrow suppression (megaloblastic anemia, Leukopenia) and neurological deficiencies (peripheral neuropathies, pernicious anemia). A good scavenger system is required. Nitrous oxide may be contraindicated in the following patients:
- First trimester of pregnancy.
- History of respiratory illness or chronic obstructive pulmonary disease (COPD).
- Gastrointestinal obstructions
- Possible pneumothorax.
- Cobalamin (vitamin B-12) deficiency.
- History of mental health conditions.
- History of substance use disorders.
Asthma is not a contraindication to nitrous use, and in fact may help by alleviating stress/anxiety which can serve as a trigger.
Respiratory air volumes can be measured with a spirometer. Taller people, fit people or people who live at higher altitudes will have larger volumes. The volumes you should know:
- Tidal volume (TV) – that volume of air moved into or out of the lungs during quiet breathing (normal breathing).
- Expiratory reserve volume (ERV) – the maximal volume of air that can be exhaled from the end-expiratory position (in addition to regular breathing).
- Inspiratory reserve volume (IRV) – the maximal volume that can be inhaled from the end-inspiratory level (in addition to regular breathing).
- Vital capacity (VC) – the volume of air breathed out after the deepest inhalation. TV+ERV+IRV.
- Residual volume (RV) – the volume of air remaining in the lungs after a maximal exhalation. RV cannot be measured using spirometry.
- Total lung capacity (TLC) – the volume in the lungs at maximal inflation, the sum of VC and RV. VC+RV.
VOLATILE LIQUID ANESTHETICS
Inhalational anesthetics are volatile chemical compounds used in general anesthesia. An anesthetic vaporizer and inhalation delivery system is used to administer a titrated dose. The ideal anesthetic agent provides smooth and reliable induction and maintenance of general anesthesia with minimal adverse effects. Desflurane, Isoflurane, Sevoflurane, Halothane, and Enflurane are examples. Volatile anesthetics are not a concern for COPD patients since they are all bronchodilators and vasodilators. Desflurane requires heating in addition to a vaporizer for inhalation administration (the rest only require a vaporizer).
All potent inhalation agents and succinylcholine are capable of triggering malignant hyperthermia (MH), which initiates the release of stored calcium within muscle cells. Symptoms include muscle rigidity, high fever, acidosis, myoglobinuria, hypermetabolism, unstable blood pressure, tachypnea, and tachycardia. Susceptibility can occur due to at least six genetic mutations, and if encountered can be fatal. Treatment is with dantrolene, rapid cooling and basic life support.
INTRAVENOUS AND ORAL ANESTHETICS
Barbiturates are used as hypnotics and sedatives, acting by depressing the central nervous system (CNS) through decreasing the rate of dissociation of gamma-aminobutyric acid (GABA) at its receptor. GABA is the main inhibitory neurotransmitter in the CNS. Barbiturates potentiate the effect of GABA at the receptor. Prolonged receptor activation causes the associated chloride channel to remain open for longer (increased duration), decreasing neuronal firing. Barbiturates also block glutamate receptors, glutamate being the main excitatory neurotransmitter in the CNS. Barbiturates are weak analgesics but strong anesthetics. They have been used as “truth serums”. A patient can develop tolerance and dependence, and barbiturates have a high potential for misuse and overdose (Jimi Hendrix and Marilyn Monroe). Examples of barbiturates
- Phenobarbital – long acting, hypnotic, used to treat anxiety and insomnia.
- Amobarbital (Amytal) – intermediate-acting, used to treat anxiety, epilepsy, and insomnia.
- Butabarbital (Fioricet) – intermediate-acting, used to treat anxiety and insomnia.
- Pentobarbital (Numbutal) – short-acting, preanesthetic, used to treat insomnia, and control of convulsions in emergencies. Has been used for executions of convicted criminals.
- Secobarbital (Seconal) – short acting, preanesthetic, used to treat insomnia and epilepsy. Has been used in physician-assisted suicide.
- Sodium thiopental (Pentothal) – ultra short acting, used in the induction phase of general anesthesia, rapid onset (high lipid solubility). Has been used for executions of convicted criminals.
- Methohexital (Brevital) – ultra short acting, used in the induction phase of general anesthesia, rapid onset (high lipid solubility).
- Thiamylal (Surital) – ultra short acting, used in the induction phase of general anesthesia, rapid onset (high lipid solubility).
Benzodiazepines are psychoactive drugs used as sedatives, hypnotics, anxiolytics, anticonvulsants and muscle relaxants. Benzodiazepines potentiate the effect of GABA at the receptor. Prolonged receptor activation causes the associated chloride channel to remain open more frequently (increased frequency), decreasing neuronal firing. They can be used for short term treatment of insomnia. Higher dosages can cause anterograde amnesia (not retrograde) and dissociation. Because of their muscle relaxant action, benzodiazepines may cause respiratory depression and are contraindicated in people with myasthenia gravis, sleep apnea (cessation of breathing), bronchitis, and COPD. Diazepam (Valium) is contraindicated for use in patients with narrow angle glaucoma.
Patients can develop tolerance and dependence, and withdrawals can be life threatening. Benzodiazepines have a high potential for misuse. They are considered less toxic than barbiturates but overdose is still possible. A reversal agent flumazenil (Anexate) is available, acting as a competitive antagonist at the GABA receptor. The halflife of flumazenil is short (~30 mins) and post-surgical monitoring is necessary because flumazenil can mask the apparent metabolization of the drug. Benzodiazepines like Versed is the most commonly used pediatric premedication before general anesthesia. They can be classified as short, intermediary, or long acting.
- Triazolam (Halcion) – is a short-acting benzodiazepine generally only used as a sedative to treat severe insomnia.
- Midazolam (Versed) – is a short-acting benzodiazepine in adults with an elimination half-life of 1.5–2.5 hours. Effects last for between one and six hours. Used to induce sleep, reduce anxiety, and cause amnesia.
- Alprazolam (Xanax) – is an intermediate-acting benzodiazepine most commonly used in the short term management of anxiety disorders.
- Temazepam (Restoril) – is an intermediate-acting benzodiazepine used to induce sleep. The effects generally begin within an hour and last for up to eight hours. It appears most toxic in overdose when used with other benzodiazepines. Temazepam has very good bioavailability, with almost 100% being absorbed when taken orally.
- Diazepam (Valium) – is a long-acting benzodiazepine commonly used to treat anxiety, seizures, alcohol withdrawal syndrome, benzodiazepine withdrawal syndrome, muscle spasms, insomnia, and restless legs syndrome.
- Lorazepam (Ativan) – is a long-acting benzodiazepine used to treat anxiety disorders, insomnia, first-line treatments for active seizures, alcohol withdrawal, and chemotherapy-induced nausea and vomiting.
Propofol (Diprivan) is a short acting (highly lipophilic) intravenous sedative/hypnotic often used for induction and maintenance in general anesthesia. It can also be used in active seizure cases where Lorazepam didn’t work. There is a lower incidence of nausea and vomiting with propofol. It starts working in less than two minutes, effects take about 5-10 minutes to wear off. Propofol is called the milk of amnesia because of its color, and it’s the drug that killed Michael Jackson.
Ketamine is a potent, short acting NMDA receptor antagonist that is a derivative of the recreational hallucinogenic drug Phencyclidine (PCP or angel dust). It is used for induction and maintenance in general anesthesia. Ketamine produces dissociative anesthesia (dissociation between thalamic and limbic systems) where the patient may appear to be awake, in a trance-like state leading to pain relief, sedation, and memory loss. In case be used in emergency or intensive care settings for pain relief. Ketamine is often used by EMS personnel because heart function, breathing, and airway reflexes are not depressed. Ketamine stimulates the sympathetic nervous system, resulting in cardiovascular stimulation and bronchodilation. Hallucinations are a common side effect. Ketamine has a high abuse potential.
Chloral Hydrate is commonly used in pediatric sedation, acting on the central nervous system to induce sedation and sleepiness but (at normal doses) does not affect breathing, reflexes or blood pressure. The major active metabolite is trichloroethanol. Onset within 30 mins when given orally and lasts 4-8 hours. There is often a period of excitement and irritability before sedation.
The antecubital fossa or dorsum of the hand are good places for venipuncture. The median cubital (most commonly used), basilic or cephalic veins are targeted in the antecubital fossa. A 21 gauge needle is commonly used. In the case of Diazepam (Valium) it is injected at the rate of 1ml (5mg) per minute. Three common signs indicating the optimum level of sedation has been reached with Diazepam include blurring vision, slurring of speech, and 50% ptosis (Verrill’s sign).
Possible complications of IV use include hematoma, fluid leaking into surrounding tissues (missed vein), venospasm (burning sensation), and phlebothrombosis (inflammation + clot). Virchow’s triad describes the three factors that are thought to contribute to thrombosis, which are hypercoagulability, hemodynamic changes (turbulence, stasis), and endothelial injury or abnormality. The clinical features of deep vein thrombosis (DVT) are calf swelling, sudden dyspnea (difficulty breathing) and tachypnea, chest pain, and possibly fever. DVT can be serious and immediate systemic anticoagulation therapy should start. The affected limb is elevated.
COPD
Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease that causes obstructed airflow from the lungs, leading to shortness of breath and a cough that produces sputum. The most common cause of COPD is tobacco smoking. Rarely, emphysema is caused by a protein deficiency (alpha-1-antitrypsin deficiency emphysema). COPD treatment includes smoking cessation, respiratory rehabilitation, inhaled bronchodilators and steroids. The two diseases that account for the majority of COPD patients are emphysema and chronic bronchitis, and they often occur together.
Emphysema occurs when the degeneration of alveoli causes enlarged air sacs leading to air trapping. The main symptom is dyspnea (shortness of breath, difficulty expelling air). Breathing is assisted by pursed lips and use of accessory respiratory muscles, but minimal cyanosis. Patient’s are described as “pink puffers”. They exhibit prolonged expiratory time and may speak with short, jerky sentences. They may appear thin and barrel chested, and usually there are no adventitious sounds heard on auscultation.
Chronic Bronchitis is an inflammation of the lining of the bronchial tubes causing mucus to inhibit adequate perfusion (cyanosis). Patients are described as blue bloaters. The strain on the heart can lead to cardiac enlargement and ultimately right sided heart failure (peripheral edema). The major symptom is a productive cough. Patients with chronic bronchitis are susceptible to pulmonary infections, edema with weight gain, and respiratory/cardiac failure. Coarse rhonchi (low-pitched wheezes/rattling) and wheezing may be heard on auscultation. They usually have elevated hemoglobin levels. Cor pulmonale (enlarged right ventricle), bronchogenic carcinoma and squamous metaplasia is linked to chronic bronchitis.
Bronchial asthma is a chronic inflammatory disorder marked by airway hyperreactivity, dyspnea and wheezing expiration caused by episodic narrowing of the airways. Treatment includes long-term treatment with inhaled corticosteroids and bronchodilators such as beta2 sympathomimetics for acute attacks.
Bronchiectasis is a condition where the bronchial tubes are permanently damaged, widened, and thickened. Signs and symptoms include copious purulent sputum, hemoptysis, and recurrent pulmonary infections.
