BASICS: POTENCY, DURATION AND ONSET OF ACTION OF LOCAL ANESTHETICS

POTENCY:

Is affected by several factors including:

Hydrogen ion balance
Fiber size, type, and myelination
Vasodilator/vasoconstrictor properties (affects rate of vascular uptake)
Frequency of nerve stimulation
pH (acidic environment will antagonize the block)
Electrolyte concentrations (hypokalemia and hypercalcemia antagonizes blockade)

Lipid solubility.

DURATION OF ACTION

Is associated with lipid solubility.
Highly lipid soluble local anesthetics have a longer duration of action due to decreased clearance by localized blood flow and increased protein binding.

ONSET OF ACTION

Local anesthetics are weak bases and contain a higher ratio of ionized medication compared to non- ionized.
Increasing the concentration of non-ionized local anesthetic will speed onset.
In general, local anesthetics with a pKa that approximates physiologic pH have a higher concentration of non- ionized base resulting in a faster onset.
On the other hand, a local anesthetic with a pKa that is different from physiologic pH will have more ionized medication which slows onset.
For example, the pKa for lidocaine is 7.8 and 8.1 for bupivacaine. Lidocaine is closer to physiologic pH than bupivacaine. Lidocaine has a greater concentration on non-ionized local anesthetic than bupivacaine which results in a faster onset.
Non-ionized and ionized portions of local anesthetic solution exert distinct actions.
Lipid soluble, non-ionized form of the local anesthetic penetrates the neural sheath and membrane.
In the cell, the non-ionized and ionized forms equilibrate.
The ionized form of the local anesthetic binds with the sodium channel. Once “bound” to the sodium channel, impulses are not propagated along the nerve.

Clinically, onset of action is not the same for all local anesthetics with the same pKa. This is due to the intrinsic ability of the local anesthetic to diffuse through connective tissue.

So in general, local anesthetics with a pKa closest to the physiological pH generally have a higher concentration of non-ionized molecules and a more rapid onset.

Two notable exceptions are chloroprocaine and benzocaine. Chloroprocaine has a high pKa and rapid onset. Benzocaine does not exist in an ionized form and exerts its effects by alternate mechanisms.

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XENON – THE STRANGER

Colorless, odourless, tasteless gas

Four times denser than air.

Density and viscosity are substantially higher than those of other inhalational anaesthetics.

Occurs in extremely low concentrations (0.0875 ppm) in the atmosphere, hence its name from the Greek ‘xenos’ meaning ‘stranger’.

Xenon has been used experimentally as an anaesthetic for more than 50 years

Recently there has been a renewed interest in xenon as a safe, effective and more environmentally friendly substitute for nitrous oxide (Sanders et al. 2003).

Manufactured by fractional distillation of liquefied air, currently at a cost of US $10 per litre (i.e. about 2,000 times the cost of producing N2O). This high cost is the major factor limiting its more widespread use, even when used in low-flow delivery systems.

Xenon has many of the properties of an ideal anaesthetic.

Its blood/gas partition coefficient (0.12) is lower than that of any other anaesthetic, giving rapid induction and emergence.

It is unlikely to be involved in any biochemical events in the body, and is not metabolised.

Xenon causes no significant changes in myocardial contractility, blood pressure or systemic vascular resistance, even in the presence of severe cardiac disease (Sanders et al. 2005).

The unique combination of analgesia, hypnosis, and lack of haemodynamic depression in one agent would make xenon a very attractive choice for patients with limited cardiovascular reserve

In contrast to other inhaled anaesthetic agents, xenon slows the respiratory rate and increases the tidal volume, thereby maintaining minute ventilation constant.

Airway pressure is increased during xenon anaesthesia, due to its higher density and viscosity rather than direct changes in airway resistance (Baumert et al 2002).

Because of its high cost xenon must be used in low-flow closed circuits. Crucial to this method of administration is accurate measurement of the concentration of xenon in the circuit. This measurement is generally difficult as xenon is diamagnetic and does not absorb infrared radiation (commonly used method to measure the concentrations of other agents), and its low reactivity precludes the use of specific fuel cell or electrode-type devices.

Xenon conducts heat better than other gases, and a technique based on thermal conductivity has proved to be effective (Luginbuhl et al 2002).

Because xenon is heavier than air, the speed of sound is slower in xenon than that in air, and this difference has been also been used to measure xenon concentration.

Because xenon is a normal constituent of the atmosphere, it does not add to atmospheric pollution when emitted from the anaesthesia circuit. This is in contrast to the other inhalational anaesthetics, which have ozone-depleting potential and pollute the atmosphere when released from the anaesthesia system (Marx et al. 2001).

On a molecular basis, N2O is 230 times more potent as a greenhouse gas than carbon dioxide. N2O released as a waste anaesthetic contributes roughly 0.1% of total global warming. The lifetime of N2O in the atmosphere is long—approximately 120 years.

The anaesthetic actions of xenon are thought to result primarily from noncompetitive inhibition of NMDA receptors (De Sousa et al. 2000), a property it shares with nitrous oxide.

In common with other NMDA receptor antagonists, xenon appears to have neuroprotective properties (Sanders et al. 2003).

Xenon is also an excellent analgesic, an action mediated by NMDA receptors (De Sousa et al. 2000).

Xenon also inhibits the plasma membrane Ca2+ pump, altering neuronal excitability and inhibiting the nociceptive responsiveness of spinal dorsal horn neurones.

#xenon ,#InhalationalAnaesthesia ,#GlobalWarming ,#Ozone , #OzoneDepletion ,#NobleGas ,#anaesthesia ,#ClinicalPharmacology,#pharmacology ,#research

(Reference : Jürgen Schüttler • Helmut Schwilden Modern Anesthetics ,Handbook of Experimental Pharmacology, vol 182)

CONDITIONS ASSOCIATED WITH AUTONOMIC DYSFUNCTION

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DIAPHRAGMATIC EVENTRATION

Typically affects only a segment of the hemidiaphragm

Is due to incomplete muscularisation of the diaphragm with a thin membranous sheet replacing the normal diaphragmatic muscle.

Over time this region stretches and on inspiration does not contract normally.

Sudden rupture can occur with increase in intra-abdominal pressure (e.g. coughing, straining during light anesthesia or extubation etc)

True rupture (if it happens) – Effects:

Mass effect of the abdominal viscera–>direct compression of the heart, mediastinal shift

Compression of vena cava and pulmonary veins–> impairs venous return, decreased cardiac output.

So we should maintain adequate depth of anaesthesia

Avoid Nitrous oxide (expansion of intra-abdominal viscera can impair the circulation and respiration)

Reference: Anaesthetic Management of an Adult Patient with Diaphragmatic Eventration
Azhar Rehman*, Zafar Ali Mirza, Saad Yousuf and Asma Abdus Salam

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POSTOPERATIVE COGNITIVE DYSFUNCTION – RISK FACTORS

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PROJECT THE RAYS CORRECTLY: Basic facts about projection in X ray films

A postero-anterior (PA) projectionn will not produce as much magnification of the heart and mediastinum as an antero-posterior (AP) projection. So PA films are the preferred ones. Here the scapula is rotated; so the lung fields are clear.

A PA film is taken with the film cassette in front of the patient and the beam delivered from behind with the patient in an upright position.

Portable films and those taken in ICUs are all AP projection. All anterior structures appear magnified—heart, mediastinum, sternum, clavicles, and ribs

The supine position causes distension of the upper lobe blood vessels, which may be confused with elevated left atrial pressure

A lateral X-ray is useful in viewing retrosternal and chest wall lesions, localising lesions in the AP dimension, locate lesions behind the left side of the heart or in the posterior recesses of the lungs. Lateral decubitus—used in diagnosing very small collection of air or fluid in the pleural space.

A left lateral (with the left side of the chest against the film and the beam projected from the right) is the standard projection.

The heart is magnified less with a left lateral as it is closer to the film.

To visualize lesions in the left hemithorax, obtain a left lateral film and for right-sided lesions a right lateral.

Expiratory films are used to assess air trapping in bronchial obstruction such as a foreign body.

A pneumothorax always appears larger on an expiratory film and occasionally a small pneumothorax may only be visible on expiration.

Films if accidentally taken in expiration, can result in spurious magnifcation of the heart and mediastinum.

  • PROJECTION: The different projections of importance to us are Postero Anterior (PA), Antero Posterior (AP), Lateral, Supine, and Lateral decubitus.
  • ROTATION: An image is not rotated if the clavicular heads are equidistant to the
    corresponding thoracic spine
  • INSPIRATION: An inspiratory picture shows a ‘lot of lung’. In inspiratory films the
    level of the diaphragm is at the level of ribs 5/6 anteriorly and 8/10
    posteriorly. (AR6PR10)
  • PENETRATION: A film is adequately penetrated if the vertebral bodies can be
    visualised against the cardiac silhouette

A normal chest radiograph can be summarised as ‘…the trachea is central and the hila are normal. Lung fields are clear with no air or fluid collection. Heart and mediastinum appear normal and not displaced. There is no free air under the diaphragm, and the angles are clear. Also, the bones and soft tissues appear normal…’

–>Before diagnosing a CXR as normal, look at the areas where
pathology is commonly missed.

*Apices (including behind the 1st rib and clavicle)—small pneumothoraces and masses

*Hila—masses and lymph nodes; left hilum is 1–2 cm higher than right

*Behind the heart—left lower lobar collapse and hiatus hernia

*Below the diaphragm—free gas

*Soft tissues—breast shadow or absence (look for lung and bone metastasis)

#xray ,#radiology ,#imaging , #XrayBasics , #anaesthesia

Reference: Radiology for Anaesthesia and Intensive Care (Richard Hopkins, Carol Peden and Sanjay Gandhi)

THE BASICS OF RESPIRATORY PHYSIOLOGY

CO2 is the most important stimulus for respiration

Receptors for CO2 are found in the medulla of the brain (central chemoreceptors)

Receptors for O2 are found mainly in carotid and aortic bodies

CO2 is the more important gas as the body has more capacity to store CO2 than O2 or hydrogen ions

In normal people at sea level, only 10% of the respiratory drive is due to hypoxic stimulation.

Unlike the central stimulation of hypercapnia, hypoxia causes central depression of the respiratory drive.

Acidosis (high H+ / low blood pH) stimulates respiration; conversely alkalosis depresses it.

For gas exchange, the lungs provide an interface of total surface area about 55 m2 via 700 million alveoli

Alveolar ventilation’ is that part of the total ventilation (i.e. all gas entering the lungs) that participates in gas exchange with pulmonary capillary blood; it is equal to total ventilation minus the ventilation of the conducting airways (i.e. dead-space ventilation).The average alveolar ventilation is about 4 L/min.

The alveolar–arterial oxygen gradient ( P(A-a)O2 ) is a measure of the oxygen that has reached the arterial blood supply as a ratio of the total oxygen in the alveoli. It is a useful index of pulmonary gas exchange function.

This requires that three elements are working correctly:

  1. Circulatory anatomy is normal. Anomalies such as ASD & PDA can cause anatomical shunting, i.e. venous blood passes through routes that are not exposed to alveolar air
  2. Ventilation and perfusion are matched
  3. The respiratory membrane allows sufficient free diffusion of gases between air and blood. A diffusion defect impairs the alveolar–capillary membrane, e.g. in interstitial lung fibrosis

In a healthy individual breathing room air (at FiO2 0.21) the PO2 in alveolar air is 104 mmHg and in arterial blood 95 mmHg . PAO2 exceeds PaO2 by 15 mmHg .Thus, at an FiO2 of 21, the P(A–a)O2 is 15 mmHg

In blood, CO2 is present as:

Dissolved in blood plasma (5.3% in arterial blood)

Bound to haemoglobin as carbaminohaemoglobin within erythrocytes (4.5%)

In the form of bicarbonate attached to a base (90%)

Reference:”Understanding ABGs & Lung Function Tests” Muhunthan Thillai, Keith Hattotuwa

Drugs that act as Respiratory stimulants/ depressants

Drugs that act as Respiratory stimulants

Acetazolamide
Aminophyllines
Doxapram
Progesterone
Salicylates

Drugs that act as Respiratory depressants

Alcohol
Anaesthetics
Anticholinergics
Antihistamines
Barbiturates
Benzodiazepines
Opioids

NATURALLY OCCURRING OPIOIDS

MNEMO>

P͎A͎P͎A͎ C͎a͎r͎e͎s͎ M͎O͎R͎e͎ T͎H͎a͎n͎ N͎A͎T͎U͎R͎E͎

PAPAVERINE CODEINE MORPHINE THEBAINE

Do you know what CVS anomaly you have to rule out, if you get a patient with TURNERS SYNDROME, for any surgery?

MNEMO>

Aorta is the vessel, which ‘TURNs back’

Answer: Coarctation of Aorta, Aortic Valvular Disease!!