📖 Anaesthesia

Pain: sensory and emotional experience associated with actual or potential tissue damage

1. Components: sensory (objective characteristics of pain e.g., location, duration, intensity; thermal, mechanical, or chemical) and motivational/affective (associated with past experience, fear, suffering, anxiety, culture)

2. Anatomy and physiology: nociceptors specialized to convey noxious stimuli (mechanical, chemical, thermal) 

a. Hyperalgesia: exaggerated pain response to stimulus that was previously painful. 

i.  Primary: nociceptors in area of tissue damage fire or due to algesic chemicals (bradykinin, SP, etc.)

ii.  Secondary: absence of local causes so due to changes in CNS that result in nociceptor firing (e.g., referred pain due to convergence)

b. Allodynia: pain caused by stimulus that is normally innocuous (non-painful); e.g., abcess- just touch, hurts

c. Fiber types: local anesthetics target Ad and C fibers

i.  A-b: myelinated cutaneous mechanoreceptor (25-50 m/s); innervates Ruffini endings

ii.  A-d: myelinated nociceptor that mediates sharp, well-localized pain (10-30 m/s)

iii. C: have Schwan cells but no myelin; nociceptor that mediates dull, poorly-localized pain (<2.5 m/s)

d. Neurotransmitters:

i.  Excitatory: glutamate (most common, works on NMDA receptors), substance P (SP, p for pain; act at neurokinin, NK, receptors), calcitonin G-receptor peptide (CGRP; co-released with SP), prostaglandins (products of cyclooxygenase), and kinins

ii.  Inhibitory: GABA (amino acid; hyperpolarizes neurons so ¯ pain sensation), monoamines (e.g., seratonin, NE), and opioids (e.g., endorphins- give runner’s high; 3 made by body: 1) b-endorphin, 2) dynorphin, 3) enkephalins; 3 receptors: 1) mu- most important for pain, 2) delta, and 3) kappa)

Treatment:

a. Opioids: indicated for moderate to severe acute (post-op) pain, chronic cancer pain, or as sedative/pain reliever during general anesthesia.  A narcotic = sleep-inducing.

i.  Mechanism of action: bind opioid receptor in spinal cord and brainstem (mu, d, and kappa; found in periaqueductal grey- area in brain with tons of opioid receptors, when activated ® ¯ pain), inhibit peripheral nociceptors, activate descending pain control system, improve affective components of pain

ii.  Side-effects: euphoria, sedation, respiratory depression, nausea/vomiting, constipation (especially with elderly), addiction, tolerance (does not remain once drug removed)

b. NSAIDS (non-steroidal anti-inflammatory drugs): indicated for mild to moderate pain that has inflammatory component, fever.  Aspirin first made in 1853 from parts of willow bark.

i. Mechanism of action: inhibits cyclooxygenase (COX) which makes prostaglandins and other inflammatory agents.  Anti-pyretic (fever-reducing) actions mediated by effects on hypothalamus- center of brain that regulates body T.

ii. Side effects: since acidic- nausea, vomiting (rare), GI bleeding, prolonged bleeding time since inhibit platelets.  Warnings if ulcer history, combining NSAIDS (® ringing in ears), and flu/chicken pox in children ® risk of Rie syndrome (fatal brain inflammation)

c. Tylenol (acetaminophen): analgesic and anti-pyretic but no significant effect on inflammation.   OD kills liver.

d. Muscle relaxants: don’t act directly on muscles; indicated for myofascial pain (muscle/CT pain) but not analgesic (not good for pain control)

i. Mechanism of action: depends on drug but most ­ GABA-mediated signals in spinal cord

ii. Side-effects: sedation, weakness

e. Anti-depressants: low-doses indicated for chronic pain that is unresponsive to conventional analgesics, 1st choice for some types of neuropathic pain.  Side effects: sedation, xerostomia, CV effects.

i.  Mechanism of action: activate descending pain control systems ® pre-synaptic a-2 receptor to ­ monoamine (NE, seratonin) in brain ® inhibit SP, glutamate, etc. release from peripheral nociceptors.

4. Descending pain modulatory pathways: neuronal cell bodies in brainstem send projections to dorsal horn where release NT that inhibit incoming pain info or decrease sensitivity of neurons in dorsal horn to that info.  Opioids and antidepressants act in part by these pathways.

Pharmacodynamics of Nitrous Oxide

Overview

Nitrous oxide (N2O), commonly known as "laughing gas," is an inhalational anesthetic used primarily for its analgesic and anxiolytic properties. Understanding its pharmacodynamics is crucial for safe and effective use in clinical settings.

Pharmacodynamics

1. CNS Depression:

   • Nitrous oxide produces nonspecific central nervous system (CNS) depression.
   • While it is classified as an inhalational general anesthetic, it provides limited analgesia, making surgical anesthesia unlikely unless concentrations that produce anoxia are reached.

2. Potency:

   • Nitrous oxide is the weakest of all inhalation agents, with a minimum alveolar concentration (MAC) of approximately 105%.
   • The MAC is a measure of the potency of an inhalation agent, defined as the concentration required to produce immobility in 50% of patients in response to a surgical stimulus.

3. Effects at Various Concentrations:

   • 30% to 50% Concentration:
     • Produces a relaxed, somnolent patient who may appear dissociated and is easily susceptible to suggestion.
     • Some patients may experience amnesia, but there is typically little alteration in learning or memory.
   • Greater than 60% Concentration:
     • Patients may experience discoordination, ataxia, giddiness, and increased sleepiness.
     • It is recommended that the concentration of nitrous oxide should not routinely exceed 50% to avoid adverse effects.

4. Titration:

   • One of the advantages of nitrous oxide is its ability to be easily titrated.
   • It can be increased for stimulating procedures (e.g., injections) and decreased during less stimulating periods (e.g., restorations).

Physiological Considerations

1. Entrapment in Gas-Filled Spaces:

   • Nitrous oxide can become entrapped in gas-filled spaces such as the middle ear, sinuses, and gastrointestinal tract.
   • This can lead to increased middle ear pressure, which is generally insignificant in patients with normal Eustachian tube function but can induce pain in patients with acute otitis media.

2. Contraindications:

   • Acute Otitis Media: Use should be avoided in patients with this condition due to the risk of increased middle ear pressure and pain.
   • Severe Behavioral Problems and Emotional Illness: Patients who are uncooperative or have a fear of "gas" may not tolerate nitrous oxide well.
   • Claustrophobia: Patients with this condition may feel uncomfortable with the nasal hood placement.
   • Maxillofacial Deformities: Conditions that prevent proper placement of the nasal hood can contraindicate its use.
   • Nasal Obstruction: Conditions such as upper respiratory infections, nasal polyps, or a deviated septum can hinder effective administration.
   • Chronic Obstructive Pulmonary Disease (COPD): Patients with COPD may have difficulty with nitrous oxide due to respiratory issues.
   • Pregnancy: Caution is advised when using nitrous oxide in pregnant patients.
   • High Oxygenation Situations: Situations where high oxygenation is inadvisable, such as during Bleomycin therapy, contraindicate the use of nitrous oxide.