Sodium-chloride symporter inhibitor.

The thiazide sensitive sodium chloride symporter is inhibited by thiazides at the proximal portion of the distal convoluted tubule leading to increased sodium and water excretion. Increased delivery of sodium to the distal portion of the distal convoluted tubule promotes potassium loss. This is why thiazides are associated with hyponatraemia and hypokalaemia.

Carbonic anhydrase inhibitors are used mainly in the treatment of glaucoma. They act on the proximal convoluted tubule to promote bicarbonate, sodium and potassium loss.

Sodium potassium chloride symporter is inhibited by Loop diuretics.
Epithelial sodium channels are inhibited by Amiloride.
Drugs which lead to nephrogenic diabetes insipidus such as lithium and demeclocycline, are Inhibitors of vasopressin.

A significant early feature of the metabolic response to trauma and surgery is hyperglycaemia. It is due to an increased glucose production and decreased glucose utilisation bought on by neuroendocrine stimulation. Catecholamines, Growth hormone, ACTH and cortisol, and Glucagon are all increased.

There is also a decreased insulin sensitivity peripherally and an inhibition of insulin production from the beta cells of the pancreas. These changes lead to hyperglycaemia.

The stress response to endoscopic surgery will only be prevented with use of high dose opioids or central neuraxial block at anaesthesia.
To reduce the risk of inducing hyperchloremic acidosis, Ringer’s lactate/acetate or Hartmann’s solution is preferred to 0.9% sodium chloride as routine maintenance fluids.

Though it has been suggested that administration of Hartmann’s solution to patients with type 2 diabetes leads to hyperglycaemia, one Litre of Hartmann’s solution would yield a maximum of 14.5 mmol of glucose. A rapid infusion of this volume would increase the plasma glucose by no more than 1 mmol/L..

Dexamethasone, a glucocorticoid, produces hyperglycaemia by stimulating gluconeogenesis . Glucocorticoids are agonists of intracellular glucocorticoid receptors. Their effects are mainly mediated via altered protein synthesis via gene transcription and so the onset of action is slow. The onset of action of dexamethasone is about one to four hours and therefore would NOT contribute to the hyperglycaemia in this patient in the time given.

0.9% Normal saline with or without adrenaline is the usual irrigation fluid. With this type of surgery, systemic absorption is unlikely to occur.

Fentanyl is not likely the primary cause of hyperglycaemia in this patient. In high doses (50 mcg/Kg) it has been shown to reduce the hyperglycaemic responses to surgery.

While the brain only weighs 3% of the body weight, 15% of the cardiac output goes towards the brain.

Between mean arterial pressures (MAP) of 60-130 mmHg, autoregulation of cerebral blood flow (CBF) occurs. Exceeding this, the CBF is maintained at a constant level. This is controlled mainly by the PaCO2 level, and the autonomic nervous system has minimal role.

Beyond these limits, the CBF is directly proportional to the MAP, not the systolic blood pressure.

The portal vein arises from the splenic and mesenteric veins, and is the biggest vessel in the portal venous system, accounting for about 75% of the hepatic blood flow.

It is responsible for draining blood from parts of the gastrointestinal system, the spleen, the pancreas and the gallbladder into the liver.

The normal peak inspiratory flow in healthy individuals is 20-30 L/min during each normal tidal ventilation. This is expected to increase with greater respiratory rate and deeper inspiration.

Face masks are used to facilitate the delivery of oxygen from a breathing system to a patient. Face masks can be divided into two types: fixed performance or variable performance devices.

In fixed performance devices (also known as high air flow oxygen enrichment or HAFOE), fixed inspired oxygen concentration is delivered to the patent, independent and greater than that of the patient’s peak inspiratory flow rate (PIFR). No random entrainment is expected to occur at the time of PIFR, hence, the oxygen concentration in HAFOE devices is not dependent on the patient’s respiratory pattern.

Moreover, in HAFOE masks, the concentration of oxygen at a given oxygen flow rate is determined by the size of the constriction; a device with a greater entrainment aperture delivers a lower oxygen concentration. Therefore, a 40% Venturi device will have lesser entrainment aperture when compared to a 31% Venturi. Venturi masks allow relatively fixed concentrations of supplemental oxygen to be inspired e.g. 24%, 28%, 31%, 35%, 40% and 60% oxygen. These are colour coded and marked with the recommended oxygen flow rate.

Variable performance devices deliver variable inspired oxygen concentration to the patient, and is dependent on the PIFR. The PIFR can often exceed the flow rate at which oxygen or an oxygen/air mixture is supplied by the device, depending on a patient’s inspiratory effort. In addition, these masks allow expired air to be released through the holes in the sides of the mask. Thus, with increased respiratory rate, rebreathing of alveolar gas from inside the mask may occur.

The ileocolic artery is the terminal branch of the superior mesenteric artery. It supplies:
1. terminal ileum
2. proximal right colon
3. cecum
4. appendix (via its branch of the appendicular artery)

As veins accompany arteries in the mesentery and are lined by lymphatics, high ligation is the norm in cancer resections—the ileocolic artery branches off the SMA near the duodenum.

A decrease in the functional residual capacity (FRC) is the most important physiologic change to consider for such patients.

FRC is the sum of the expiratory reserve volume and the residual volume. It is the resting volume of the lung, and is an important marker for lung function. During this time, the alveolar pressure is equal to the atmospheric pressure. When morbidly obese individuals lie supine, the FRC decreases by as much as 40% because the abdominal contents push the diaphragm into the thoracic cavity.

Chest wall compliance is expected to reduce because of fat deposition surrounding adjacent structures.

Inspiratory reserve volume (IRV) is expected to increase, and peak expiratory flow is expected to decrease, however the decrease in FRC is more important to consider because of the risk of hypoxia secondary to premature airway closure and ventilation-perfusion mismatch.

The standard error of the mean (SEM) is a measure of the spread expected for the mean of the observations – i.e. how ‘accurate’ the calculated sample mean is from the true population mean. The relationship between the standard error of the mean and the standard deviation is such that, for a given sample size, the standard error of the mean equals the standard deviation divided by the square root of the sample size.

SEM = SD / square root (n)

where SD = standard deviation and n = sample size

Therefore, the SEM gets smaller as the sample size (n) increases.

If we want to depict how widely scattered some measurements are, we use the standard deviation. For indicating the uncertainty around the estimate of the mean, we use the standard error of the mean. The standard error is most useful as a means of calculating a confidence interval. For a large sample, a 95% confidence interval is obtained as the values 1.96×SE either side of the mean.

A 95% confidence interval:

lower limit = mean – (1.96 * SEM)

upper limit = mean + (1.96 * SEM)

Results such as mean value are often presented along with a confidence interval. For example, in a study the mean height in a sample taken from a population is 183cm. You know that the standard error (SE) (the standard deviation of the mean) is 2cm. This gives a 95% confidence interval of 179-187cm (+/- 2 SE).

Hence, it would be wrong to say that confidence levels do not apply to standard error of the mean.

Work up bias involves comparing the novel diagnostic test with the current standard test. A portion of the patients undergo the standard test while others undergo the new test as the standard test is costly. The result can be alteration in specify and sensitivity.

Recall bias is specifically appropriate to the case control studies that is when ever the memories retrieved by the participants differ in accuracy.

Not publishing the results of a valid study just because they are negative or uninteresting can be termed as publication bias.

When information gathering is ill suited with respect to time i.e. collecting the data regarding a fatal disease many years after the death of its patients, it is termed as Late – look bias.

The case in point is an instance of lead time bias when upon comparing two tests, one is able to detect the condition earlier than the other but the overall outcome doesn’t change. There is a possibility that this will make the survival rates for the newer test look more promising.

Propofol is cleared at the fastest rate at the rate of 60ml/kg/min.

Clearance rate of other drugs are as follows:
– Thiopental: 3.5 ml/kg/min
– Methohexitone: 11 ml/kg/min
– Ketamine: 17 ml/kg/min
– Etomidate: 10-20 ml/kg/min

There are 4 different types of globin chains which surround 4 heme molecules in haemoglobin (Hb) – α (alpha), β (beta), γ (gamma), and δ (delta)
α chains are essential.
δ2β2 and β2γ2 are not found in a healthy adult.
97% of the Hb in a healthy adult is made of α2β2 (2 α chains and 2 β chains).
α2δ2 accounts for around 1.5-3% of the adult Hb.
α2γ2 accounts for less than 1%.

With respect to oxygen transport in cells, almost all oxygen is transported within erythrocytes. There is limited solubility and only 1% is carried as solution. Thus, the amount of oxygen transported depends upon haemoglobin concentration and its degree of saturation.

Haemoglobin is a globular protein composed of 4 subunits. Haem is made up of a protoporphyrin ring surrounding an iron atom in its ferrous state. The iron can form two additional bonds – one is with oxygen and the other with a polypeptide chain. There are two alpha and two beta subunits to this polypeptide chain in an adult and together these form globin. Globin cannot bind oxygen but can bind to CO2 and hydrogen ions. The beta chains are able to bind to 2,3 diphosphoglycerate. The oxygenation of haemoglobin is a reversible reaction. The molecular shape of haemoglobin is such that binding of one oxygen molecule facilitates the binding of subsequent molecules.

Recommendations from the British Thoracic Society for acute severe asthma or life-threatening asthma are:

1. Give controlled supplementary oxygen to all hypoxemic patients with acute severe asthma titrated to maintain a SpO₂ level of 94 98%.
2. Use high-dose inhaled ?₂ agonists as first-line agents in patients with acute asthma and administer them as early as possible. Reserve
intravenous ?₂ agonists for those patients in whom inhaled therapy cannot be used reliably.
3. Give steroids in adequate doses to all patients with an acute asthma attack.
4. Add nebulized ipratropium bromide (0.5 mg 4–6 hourly) to ?₂ agonist treatment for acute severe or life-threatening asthma or those with a poor initial response to ?₂ agonist therapy.
5. Consider aminophylline for children with severe or life-threatening asthma unresponsive to maximal doses of bronchodilators and steroids.

A review (including 12 case reports, three RCTs, and five other observational studies) of ketamine use in adults and children in status asthmaticus reported that ketamine is a potential bronchodilator. Still, prospective trials are needed before conclusions about effectiveness can be drawn.

Heliox has no place in the current guidelines issued by the British Thoracic Society.

According to the Safe Anaesthesia Liaison Group, the most important factor to consider the cannula access, and if the patient is properly receiving the total intravenous anaesthesia. The cannula access must be regularly checked for kinks, leaks and disconnections.

Below are the safety precautions and policies to be followed for total intravenous anaesthesia among children and adults:

When administering TIVA, a non-return valve must be used on any intravenous fluid line;
When using equipment, it is essential that clinical staff know its limitations and uses;
Sites of intravenous infusions should be visible so they may be monitored for disconnection, leaks or perivenous infusion into the subcutaneous tissues; and,
Organisations must give preference to clearly labelled intravenous connectors and valves.

The bispectral index (BIS) is one of several systems used in anaesthesiology as of 2003 to measure the effects of specific anaesthetic drugs on the brain and to track changes in the patient’s level of sedation or hypnosis. It is a complex mathematical algorithm that allows a computer inside an anaesthesia monitor to analyse data from a patient’s electroencephalogram (EEG) during surgery. It is a dimensionless number (0-100) that is a summative measurement of time domain, frequency domain and high order spectral parameters derived from electroencephalogram (EEG) signals.

Sleep and anaesthesia have similar behavioural characteristics but are physiologically different but BIS monitors can be used to measure sleep depth. With increasing sleep depth during slow-wave sleep, BIS levels decrease. This correlates with changes in regional cerebral blood flow when measured using positron emission tomography (PET).

BIS shows a dose-response relationship with the intravenous and volatile anaesthetic agents. Opioids produce a clinical change in the depth of sedation or analgesia but fail to produce significant changes in the BIS. Ketamine increases CMRO2 and EEG activity.

BIS is unable to predict movement in response to a surgical stimulus. Some of these are spinal reflexes and not perceived by the cerebral cortex.

BIS is used during cardiopulmonary bypass to measure depth of anaesthesia and an index of cerebral perfusion. However, it cannot predict subtle or significant cerebral damage.

30mL 0.5% bupivacaine, 1mL 1 in 1,000 adrenaline and 89mL 0.9% N. Saline is the correct answer.
Initial concentration of bupivacaine is 0.5% with a volume of 30mL

The volume is doubled (60mL) by the addition of 0.9% N. saline (30mls) and the concentration of bupivacaine is halved to (0.25%).

If the volume is doubled again (120mL) by the addition of further 0.9% N. saline (59mls) the final concentration of bupivacaine is halved again to 0.125%. Total N. saline = 89mls

The 1 mL of 1 in 1000 adrenaline has also been diluted into the final volume of 120 mL making it a 1 in 120000 concentration.

The sacral hiatus is shaped by incomplete midline fusion of the posterior elements of the distal portion of S4 and S5. This inverted U shaped space is covered by the posterior aspect of the sacrococcygeal membrane and is an important landmark in caudal anaesthetic block. Distal most portion of the dural sac and the sacral hiatus usually terminate between levels S1 and S3. The dural sac ends at the level of S2 in adults and S3 in children.

An equilateral triangle is formed between the apex of the sacral hiatus and the posterior superior iliac spines. This triangle is used to determine the location of the sacral hiatus during caudal anaesthetic block.

Charles’ Law states that there is a direct correlation between temperature and volume, where pressure and amount gas are constant. As temperature increases, volume also increases.

Boyle’s Law states that Pressure is inversely proportional to volume, assuming that temperature and amount of gas are constant. As volume increases, pressure decreases. In Dalton’s law of partial pressure, the total pressure exerted by a mixture of gases is equal to the sum of the partial pressure of the gases in mixture.

According to Henry’s Law for concentration of dissolved gases, at a constant temperature, the amount of a given gas that dissolves in a given type and volume of liquid is directly proportional to the partial pressure of that gas in equilibrium with that liquid. An equivalent way of stating the law is that the solubility of a gas in a liquid is directly proportional to the partial pressure of the gas above the liquid.

Gay-Lussac’s Law states that the pressure of a given mass of gas varies directly with the absolute temperature of the gas, when the volume is kept constant. This law is very similar to Charles’ Law, with the only difference being the type of container. Whereas the container in a Charles’ Law experiment is flexible, it is rigid in a Gay-Lussac’s Law experiment.

In anaesthesia, adductor pollicis neuromuscular monitoring with ulnar nerve stimulation is commonly used. It is the gold standard for measuring the degree of block and comparing neuromuscular blocking drugs and their effects on other muscles.

Electrodes are usually placed over the ulnar nerve at the wrist to monitor the adductor pollicis.

Neuromuscular blocking drugs have different sensitivity levels in different muscle groups.

To achieve the same level of blockade, the diaphragm requires 1.4 to 2 times the amount of neuromuscular blocking agent as the adductor pollicis muscle. The small muscles of the larynx and the ocular muscles are two other respiratory muscles that are less resistant than the diaphragm (especially corrugator supercilii).

The abdominal muscles, Orbicularis oculi, peripheral muscles of the limbs, Geniohyoid, Masseter, and Upper airway muscles are the most sensitive to neuromuscular blocking agents.

The C8-T1 nerve roots, which are part of the medial cord of the brachial plexus, form the ulnar nerve. It enters the hand via the ulnar canal, superficial to the flexor retinaculum, after following the ulnar artery at the wrist.

The nerve then splits into two branches: superficial and deep. The palmaris brevis is supplied by the superficial branch, which also provides palmar digital nerves to one and a half fingers. The dorsal surface of the medial/ulnar 1.5 fingers, as well as the corresponding skin over the hand, are also supplied by it (as well as the palmar surface).

The ulnar nerve’s deep branch runs between the abductor and flexor digiti minimi, which it supplies. It also innervates the opponens, and with the deep palmar arch, it curves around the hook of the hamate and laterally across the palm. All of the interossei, the medial two lumbricals, the adductor pollicis, and, in most cases, the flexor pollicis brevis are supplied there.

Porphyria is a group of disorders in which there is excess production and excess excretion of porphyrins and their precursors. They are usually genetic and are caused due to defects in the haem metabolic pathway. However, other factors like infection, pregnancy, mensuration, starvation may precipitate the attack.

Sulphonamides, barbiturates (methohexitone and thiopental), and phenytoin are considered to be precipitants so are not safe to use
Chloral hydrate is thought to be safe to use.
Etomidate lacks proper studies and may be used with caution but it is generally advised not to use this drug especially if other alternatives are available.

A nominal volume of 2 litres is contained in a CD cylinder. It has a pressure of 230 bar when full and contains litres 460 L of useable oxygen at STP.

For every 1000 mL 100% oxygen there will be an entrainment of 1000 mL or air (20% oxygen) in an air/oxygen mix.

The average concentration is, therefore, 120/2=60% or 0.6.