CONTEXT SENSITIVE HALF TIME [CSHT]

• Context sensitive half-time is deined as the time for the plasma concentration to fall to half of the value at the time of stopping an infusion
• The half time will usually alter in the setting of varying durations  of drug infusion
• The higher the ratio of distribution clearance to clearance due to elimination, the greater the range for context-sensitive half-time
• The longest possible context-sensitive half-time is seen when the infusion has reached steady state, when there is no transfer between compartments and input rate is the same as elimination rate
•  Draw and label the axes; draw the curve for the drug with the shortest CSHT first before plotting the others
• REMIFENTANIL: Here the elimination always dominates distribution and so there is very little variation in CSHT with time and so it is context insensitive. Draw a straight line starting from the origin and becoming near horizontal after the CSHT reaches 5 min. This demonstrates that the half time is not dependent on the length of infusion as clearance by plasma esterases is so rapid. For remifentanil the
  
  longest possible CSHT is only 8 minutes
• PROPOFOL: For propofol the clearance due to elimination is similar to that for distributioninto the second compartment, so plasma concentration falls rapidly after a propofol infusion mainly due to rapid eliminationwith a smaller contribution from distribution. Propofol is not context insensitive as its CSHT continues to rise; however it remains short even after prolonged infusions. Starting at the origin, draw a smooth curve rising steadily towards a CSHT of around 40 min after 8 h of infusion.
• ALFENTANIL: The curve rises from the origin until reaching a CSHT of 50 min
  
  at around 2 h of infusion. Thereafter the curve becomes horizontal. This shows that alfentanil is also context insensitivefor infusion durations of 2 h or longer
• THIOPENTONE SODIUM: The curve begins at the origin but rises more steeply than the others so that the CSHT is 50 min after only 30 min infusion duration. The
  
  curve should be drawn like a slightly slurred build-up exponential reaching a CSHT of 150 min after 8 h of infusion. As the CSHT continues to rise, thiopental does not become context insensitive
• FENTANYL: The most complex curve begins at the origin and is sigmoid in shape. It should cross the alfentanil line at 2 h duration and rise to a CSHT of 250 min after 6 h of infusion. Again, as the CSHT continues to rise, fentanyl does not become context insensitive.
• The maximum possible CSHT for propofol is about 20 minutes, compared with 300 minutes for fentanyl
• It is important to realize that the CSHT does not predict the time to patient awakening but simply the time until the plasma concentration of a drug has fallen by half. The patient may need the plasma concentration to fall by 75% in order to awaken, and the time taken for this or any other percentage fall to occur is known as a decrement time.
• Decrement time: The time taken for the plasma concentration of a drug to fall to the specified percentage of its former value after the cessation of an infusion designed to maintain a steady plasma concentration (time). The CSHT is, therefore, a form of decrement time when the ‘specified percentage’ is 50%.
• Although the CSHT for propofol has a maximum value of about 20 minutes, during long, stimulating surgery infusion rates will have been high and the plasma concentration when wake-up is required may be very much less than half the plasma concentration at the end of the infusion. Thus time to awakening using propofol alone may be much longer than the CSHT. This is why the TCI pumps display a decrement time rather than a CSHT.
• When using propofol infusions, the decrement time is commonly quoted as the time taken to reach a plasma level of 1.2 μg.ml−1, as this is the level at which wake up is thought likely to occur in the absence of any other sedative agents.
• It must be remembered that after one CSHT, the next period of time required for plasma concentration to halve again is likely to be much longer. This relects the increasing importance of the slower redistribution and metabolism phases that predominate after re-distribution has taken place. This explains the emphasis on half-time rather than halflife: half-lives are constant whereas half-times are not!

MEDIASTENAL TUMOURS & THE ANESTHESIOLOGIST: SPECIFIC POINTS

• A preoperative CT scan will show the site, severity, and extent of the airway compromise to assess the level and degree of obstruction.
• Assess the vocal cord function preoperatively
• Lung function tests to look for the extent of intrathoracic or extrathoracic obstruction.
• ECHO to rule out pericardial effusion and cardiac compression.
• Premedication with benzodiazepine is generally avoided if there is risk of airway compromise.
• Airway equipment—rigid bronchoscopy and difficult airway trolley, jet ventilation, cardiopulmonary bypass (CPB) should be there as standby. Femoro femoral bypass is the most common setup.
•  
• COMPLICATIONS DUE TO MASS EFFECT OF THE TUMOUR: 
•  
• Vascular compromise—SVC Obstruction ( SVCO ) and pulmonary vessel obstruction
• Laryngeal nerve palsy
• Dysphagia
• STRIDOR and airway compromise may be an important symptom
• Inspiratory stridor (laryngeal)—obstruction above the level of glottis
• Expiratory stridor (tracheobronchial)—obstruction in the intrathoracic airways
• Biphasic stridor—obstruction between glottis and subglottis or a critical obstruction at any level
• Sometimes you may have to go for a microlaryngoscopy tube (MLT)
•  
• TAKE CARE:
• Aim to avoid worsening of cardiac compression, airway occlusion, and SVC obstruction.
• IV cannula in the lower extremity
• Induction in sitting position (semi Fowler’s position)
• Inhalational (preferred choice) or IV induction agent titrated to effect
• Choose spontaneous ventilation with LMA
• Awake fibreoptic technique if intubation is necessary with a reinforced smaller calibre and longer endotracheal tube
• Postoperative airway obstruction due to airway oedema, tracheomalacia, and bleeding warrant the need for awake extubation in ITU. The following steps would aid in an uneventful extubation:
• Test for leak around the endotracheal tube cuff.
• Administer dexamethasone or chemo radiotherapy in sensitive tumours to shrink size of tumour.
• Use adrenaline nebulisers.
• Extubate over airway exchange catheters.
•  
• SVCO: challenges during anaesthesia
• Need for supplemental oxygen
• Orthopnoea—induction in the sitting-up position
• IV cannula in the lower extremity
• Airway oedema
• Mucosal bleeding
• Laryngeal nerve palsy
• Haemodynamic instability due to decreased venous return
•  
• OTHER CONCERNS 
• General anaesthesia, causes loss of intrinsic muscle tone, decreased lung volumes, and decreased transpleural pressure gradient
• Positive pressure ventilation, can precipitate severe hypotension and also increases intrathoracic tracheal compression
• Coughing, as it can cause complete airway obstruction by positive pleural pressure, increasing intrathoracic tracheal compression
• Following gas induction, the patient stops breathing and if you are unable to ventilate her: Follow difficult or failed intubation guidelines. But cricoid puncture and emergency tracheostomy are futile if the level of airway obstruction is at the intrathoracic tracheobronchial tree: Try a change in position—lateral, sitting up, or prone—to decrease the mechanical effect of the tumour. Avoid positive pressure ventilation for fear of luminal closure. Low-frequency jet ventilation with Sander’s injector or high-frequency translaryngeal jet ventilation with Hunsaker’s catheter is one option. CPB bypass and ECMO to restore oxygenation when other measures fail.
• Following chemotherapy in ICU, if patient develops hyperkalemia, Tumour Lysis Syndrome should be there in the differential diagnosis
• ALSO NOTE
• During inspiration, the intrathoracic airways expand along with the expanding lungs. In contrast, the extrathoracic airways diminish in caliber during inspiration due to their intraluminal pressure being lower than the atmospheric pressure. The reverse happens during expiration.
• Flow volume loop inupper-airway obstruction:
• Fixed lesions[extrathoracic or intrathoracic] are characterized by lack of changes in caliber during inhalation or exhalation and produce a constant degree of airflow limitation during the entire respiratory cycle. Its presence results in similar flattening of both the inspiratory and expiratory portions of the flow-volume loop
• Variable lesions are characterized by changes in airway lesion caliber during breathing. Depending on their location (intrathoracic or extrathoracic), they tend to behave differently during inhalation and exhalation.
• In the case of an extrathoracic obstructing lesion, during inspiration, there is acceleration of airflow from the atmosphere toward the lungs, and the intraluminal pressure decreases with respect to the atmospheric pressure due to a Bernoulli effect, resulting in the limitation of inspiratory flow seen as a flattening in the inspiratory limb of the flow-volume loop. During expiration, the air is forced out of the lungs through a narrowed (but potentially expandable) extrathoracic airway. Therefore, the maximal expiratory flow-volume curve is usually normal.
• Variable intrathoracic constrictionsexpand during inspiration, causing an increase in airway lumen and resulting in a normal-appearing inspiratory limb of the flow-volume loop. During expiration, compression by increasing pleural pressures leads to a decrease in the size of the airway lumen at the site of intrathoracic obstruction, producing a flattening of the expiratory limb of the flow-volume loop
• 

ETOMIDATE: THE BAD 'WOW' FACTORS

• While it continues to be used infrequently in the UK it has been withdrawn in North America and Australia
• The most notable and potentially serious side effect of etomidate administration is the suppression of adrenocortical steroid synthesis.
• It suppresses adrenocortical function by inhibition of the enzymes 11-hydroxylase and 17-hydroxylase, resulting in inhibition of cortisol and aldosterone synthesis.
• After a single bolus dose of etomidate, this adrenocortical suppression lasts approximately 6 h in healthy individuals. However in the critically ill, such suppression can last for days. In other words the situation in which it has the best cardiovascular proile is the unwell patient in whom the consequences of steroid inhibition are likely to be the most detrimental.
• Etomidate is approximately 100-fold more potent a suppressor of adrenocortical function than it is a sedative-hypnotic. Consequently, an anesthetic
  
  induction dose of etomidate represents a massive overdose with respect to its ability to suppress adrenocortical function. And etomidate’s terminal elimination half-life is rather long. Thus, after just a single anesthetic induction dose of etomidate, many hours must pass before etomidate’s concentration in the blood falls below that which suppresses adrenocortical steroid synthesis.
• It is within this mechanistic context that the strategy emerged to design analogues of etomidate
• ANALOGUES:
• MOC-etomidate[ relatively low potency and very rapid metabolism (1.) required the administration of extremely large doses]
• CPMM etomidate[ it has an onset and offset of hypnotic action that are fast (1.) ]
• Carbo etomidate[ less adrenocortical inhibition (2.)]
• MOC-carboetomidate[ combines properties (1) and (2); but it's potency
  
  is very low which means that extremely large doses would need to be administered to maintain anesthesia ]
• Involuntary movements (myoclonus) are commonly observed after etomidate administration, with some studies reporting an incidence as high as 80 % in unpremedicated patients
• It has been suggested that it occurs because etomidate depresses inhibitory neural circuits in the central nervous system sooner and at lower concentrations than excitatory circuits.
• Regardless of the mechanism, myoclonus can be significantly reduced or completely prevented by administering a variety of drugs with central nervous system depressant effects including opiates, benzodiazepines, dexmedetomidine, thiopental, lidocaine, and magnesium.
• Pain at the injection site is another common side effect and its incidence is highly dependent upon the size of the vein into which it is injected and the formulation that is used.
• Lipid emulsion and cyclodextrin formulations may reduce TRP channel activation, leading to less pain on injection
• Postoperative nausea and vomiting is common with reported incidences as high as 40 %. It has been suggested that the emetogenic trigger in etomidate is the propylene glycol solvent and not the anesthetic itself.
•  

IDEAL POSITION OF TIP OF RIGHT IJV CATHETER

• Different methods have been suggested in the literature
• Catheter tips positioned approximately 3 cm below the right tracheobronchial angle will lie in close proximity to the atriocaval junction but will remain extracardiac in location
• Pere P.W. studied correlation between the length of catheter inserted and patient's height and observed that catheters inserted through right IJV from midcervical point or lower puncture to Height/10cm ended in SVC, while those inserted more than Height/10 + 1cm, 47% ended in right atrium
• Some studies argued that the catheter tip should lie above the pericardial reflection to prevent serious and potentially lethal complications like cardiac tamponade, malignant arrhythmias, placement in coronary sinus and tricuspid valve damage. The upper limit of the pericardial reflection cannot be seen on a plain chest X-ray, but it is generally accepted to be below the carina.
• Most clinicians aim to place the catheter tip at the level of the carina with whichever formula they follow. This position carries the risk of migration, thrombosis, and malfunction.
• A recent paper has demonstrated that a catheter with its tip positioned peripheral to the atriocaval junction was more likely to undergo internal repositioning and venous thrombosis.
• The lower placement is preferred for left-sided IJV cannulations, because aiming the catheter tip placement above the pericardial reflection in this scenario is more likely to lead to oblique placement and abutment against the wall, which is a risk factor for perforation. It seems, therefore, that a free-floating catheter tip in a wider portion of the IJV is more important than placing the catheter above the pericardial reflection.
• This becomes even more relevant in the light of the observations by Schuster and colleagues¹³that the pericardium can ascend alongside the medial wall of the SVC by up to 5 cm (mean 3 cm). Thus, catheter tip placement even 3 cm above the SVC–RA junction might not obviate the risk of tamponade in all patients.
• Recently many studies have questioned the placement of the catheter tip in the middle SVC. They argue , emphasizing the importance of having a free-floating tip (not abutting the vessel wall) rather than its placement above the pericardial reflection. This can be achieved by placing the catheter tip in lower SVC and upper RA (target zone, within 2 cm above and 1 cm below the SVC–RA junction). In this position, the SVC is wider, meaning that the catheter tip is likely to float freely with minimal chance of abutment. Furthermore, a catheter placed in this position is amenable to confirmation by TOE.
• Ahn and colleagues have suggested a radiological landmark-based technique for ‘parking’ the catheter within the target zone. They adjudged the depth of CVC insertion by summing [1] the distance between the sternoclavicular joint and the carina (measured offline from the chest radiograph using an internal measuring tool available on the picture archiving and communication system), [2] the distance between the point of insertion and the sternoclavicular joint, and [3] 1.5 cm. The eventual location of the CVC tip was confirmed by TOE. The authors concluded that the catheter tip was positioned more accurately and the determined depth of CVC insertion correlated better with the actual distance from the skin insertion point to the RA–SVC junction with the radiological landmark-based technique compared with Peres’ formula of central venous catheterization via the right IJV
• N.B: Also note that from the right internal jugular and left subclavian approaches, the veins respectively take straight and gently curving trajectories to the superior vena cava. However, the right subclavian vein takes a near-right angle turn into the superior vena cava, and the left internal jugular approach incorporates two turns, one into the brachiocephalic vein and a second into the superior vena cava. These turns create potential for the venous side walls to be punctured by a dilator failing to negotiate a curve appropriately.
  
  
  
• Ref: Quest to determine the ideal position of the central venous catheter tip D. K. Tempe1,* and S. Hasija, British Journal of Anaesthesia 118 (2): 148–50 (2017)
  
  
  
  
  
  
  
  

IMPEDENCE AND RESISTANCE

• Impedance and resistance are terms used to describe the opposition to electrical current flow.
• Resistance is used to describe opposition to flow in DC circuits, whereas impedance is used for AC circuits.
• Unlike direct currents, alternating currents exhibit reactance (capacitive and inductive) because they have frequency and are phase associated.
• In AC circuits, impedance (Z) consists of a real part (ohmic resistance) and an imaginary part (reactance of an inductor or capacitor). It is measured in ohms, and is the total opposition to current flow
• Capacitors placed in DC circuitscreate an increasing resistance to current flow. This is because the charge at the negative plate of the capacitor accumulates, until maximum capacitance is reached and current flow ceases.
• Capacitors in AC circuitsallow current to flow, as the alternating direction of current flow prohibits a significant build up of charge on one of the plates.
• Reactanceis the resistance to AC that a capacitor or inductor exhibits and is inversely proportional to frequency.
• This principle is used in filters to screen out DC currents and low frequency AC.
• Inductors are coils of conducting wire wound around a ferrous or air core.
• An increasing current flowing through an inductor generates a magnetic field around it. This magnetic field in turn creates an electromagnetic force, which opposes the current flow, known as back-emf.This effect is known as inductance, and its SI unit is the henry (H).
• In a circuit where the rate of current change is 1 A/s, an inductance of one henry would generate one volt across the inductor.
• Henry (H) = Voltage (V) × Time (s) / Amperes (A)
• When the power is switched off, collapse of the magnetic field induces flow of electrons in the inductor and circuit, prolonging the flow of current for a short period.
• Inductors placed in DC circuits will initially encounter transient resistance while the magnetic field is established. Once a steady state is reached, the reactance is negligible.
• Conversely, inductors in AC circuits encounter increasing reactance proportional to the frequency. This is because the creation and subsequent reversal of magnetic field development produces a constant back-emf resisting current flow. Therefore, high-frequency AC will cause a high reactance in the inductor.
• Inductors are used to filter out high-frequency alternating currents, or to smooth out the effect of power surges in monitoring equipment
• 
  

LASERS IN MEDICINE

LASER is an acronym for Light Amplification by Stimulated Emission of Radiation.

A laser comprises a laser tube constructed from an active lasing medium that can be a gas, solid or a liquid, with a mirror at each end of the tube

Lasers produce an intense parallel beam of coherent monochromatic light (one specific wavelength of light) by the stimulated emission of photons from excited atoms

Injecting energy from an external source (pumping) causes the lasing medium to become excited. Gas lasers are excited using an electric current applied to either end of the laser tube, while solid state and liquid lasers are excited using a high intensity light source. The mirrors cause photons to bounce back and forth within the laser medium, triggering further emission of photons by the process of stimulated emission. One mirror is partially reflective which allows some photons to escape in the form of the laser beam. The beam is then focused as required

Electrons of atoms within a lasing medium normally reside in a stable low-energy level known as the ground state. Pumping excites electrons, raising them to higher energy levels. Because higher energy states are unstable in comparison to the ground state, there is a tendency for electrons to release excess energy and return to lower energy levels. This process is known as decay.

As an electron decays from the metastable to ground state, it emits a photon of energy. If this photon strikes an excited electron in the metastable state, it incites it to emit another photon, which will have the same wavelength, waveform and direction as the incident photon. They are said to be in phase and coherent.

Red and near-infrared lasers have the deepest penetration.

Carbon dioxide lasers emit infrared light and have limited penetration, but are precise and can be used for cutting and vaporising.

Argon lasers predominantly produce blue–green light at 488 and 514 nm, and are commonly used in ophthalmology.

Neodymium-doped yttrium aluminium garnet (Nd:YAG) lasers have the deepest penetration and can cut and coagulate. They are used to resect gastrointestinal and bronchial tumours, and gynaecological lesions.

LASERs are classified 1–4, 1 being least dangerous.

Most medical lasers are class 3B and class 4. They pose a high risk to staff and patients.

Lasers can ignite flammable material such as endotracheal tubes and surgical drapes. They can also cause airway and body cavity fires in the presence of high concentrations of flammable gases.

The risk of airway fires can be reduced by using the lowest inspired oxygen concentration possible that achieves suitable oxygen saturations. In addition, using laser-safe endotracheal tubes with the cuffs filled with saline and dye helps to further reduce the risk of fires. The water in the cuff acts as a heat sink to reduce the likelihood of perforating and igniting the cuff with the laser. The dye provides a visual indication in the event of cuff perforation.

The Wheatstone bridge

• The Wheatstone bridge is an electrical circuit that uses an arrangement of four resistors to measure an unknown electrical resistance.
• The typical Wheatstone bridge contains a power source, a galvanometer (G), two resistors of known resistance (R1, R2), a variable resistor (R4) and an unknown resistance, which is the one to be measured (R3). The connection across CD containing the galvanometer is known as the bridge.
• This circuit is sensitive to changes in the ratio of resistances across pairs of resistors.
• When the voltages at C and D are equal, the ratios of resistances equal each other (R1/R2 = R3/R4), no current will flow through the galvanometer and the bridge is balanced.
• By altering the resistance of the variable resistor R4 until the ratio of resistance across the limb ADB equals that of ACB, the bridge can be balanced, and no current flows across CD. By knowing the resistance required at R4 to
  balance the bridge, R3 can be calculated by using the equation R1/R2 = R3/R4
• A strain gauge is either a foil arrangement or a conductive metallic strip. In the arterial transducer, strain gauges are mounted on a diaphragm.
• The arterial pulsation is transmitted via a continuous column of fluid to the diaphragm, which causes it to stretch. The attached strain gauge will also stretch and its resistance increases. Conversely, when the diaphragm relaxes the resistance in the strain gauge falls. R3 is the strain gauge attached to the diaphragm, and the variable resistor R4 has been adjusted to match the resistance of R3 in the resting position, so that the bridge is balanced. Movement of the diaphragm would alter the resistance of R3, which unbalances the bridge and results a potential difference across CD. The resulting potential difference is quite small, so it is common to use a differential amplifier in place of the galvanometer to increase the sensitivity of the circuit in detecting the signal.

METHODS TO MEASURE THE CONCENTRATION OF A GAS

• The Rayleigh refractometer utilises the refractive index of a gas to calculate its concentration.
• Thermal conductivity is used in katharometers. In these devices, the cooling of a wire causes a change in resistance proportional to gas concentration.
• Solubility is employed in devices such as rubber strips when an increase in length accompanies gas absorption.
• Light emission features in the Raman light scattering measurement device.
• Both infrared and ultraviolet absorption are used in gas concentration measurement.

ECG EMG EEG ; THE BIOLOGICAL SIGNALS

• The movement of ions across cell membranes during the depolarisation and repolarisation of myocytes and neurones generates electric potentials.
• Silver metal electrodes covered with a layer of silver chloride gel within an adhesive sponge pad can be used to measure these potentials at the skin.
• Ion movement near the electrode–skin interface induces movement of chloride ions within the gel layer. The ion concentration gradient promotes electron production at the electrode.
• A lead wire and voltmeter attached to the electrode allows measurement of the potential relative to a reference point. The reference point is usually a second skin electrode.
• Signals are then amplified, processed and displayed.
• Skeletal and cardiac muscles have higher amplitudes than cerebral neurones.This is because the amplitude of biological potentials is proportional to the number of simultaneously depolarising cells.
• The frequency of potentials is related to the fluctuating ion activity across cell membranes.
• Skeletal myocytes which undergo tetany have high frequencies of
  up to 1 kHz.
• Conversely, cardiac myocytes have lower frequencies due to their refractory periods 

HUMIDITY AND ANESTHESIA

• Absolute humidity is the mass of water vapour present in a given volume of gas at
  defined temperature and pressure (expressed as g of H2O/m3 of gas).
• Relative humidity is the mass of water vapour present in a given volume of gas,
  expressed as a percentage of the mass of water vapour required to saturate the same volume of gas at identical temperature and pressure.
• The amount of water vapour required to saturate a known volume of gas increases with temperature, i.e. a gas saturated at 20°C contains less water than the same volume, saturated at 37°C
• Relative humidity (RH), can be calculated from the ratio of the mass of water vapour present (mP), to the mass required for satruation (mS) as
  RH = mP/mS
• If droplets are present, supersaturation has occurred and relative humidity exceeds 100%.
• From the gas laws, mass of a gas in a mixture is proportional to the partial pressure it exerts, thus: RH = water vapour pressure/ saturated water vapour pressure
• Instruments used to measure humidity are called hygrometers. Examples include:
  Regnault’s hygrometer
  Hair hygrometer
  Wet and dry bulb thermometers
  Humidity transducers