Approximately 20% of halothane and 0.02% desflurane undergo hepatic biotransformation. Desflurane, halothane, and isoflurane are metabolised in the liver by cytochrome p450 to trifluoroacetate. Through an immunological mechanism involving trifluoroacetyl hapten formation, trifluoroacetate is thought to be responsible for hepatotoxicity.

Potency of inhaled anaesthetic agents is measured using the minimal alveolar concentration (MAC). The MAC of halothane is 0.74% while that of desflurane is 6.3%. The potency can also be compared using the oil: gas partition coefficient (224 and 18.7 for halothane and desflurane respectively).

Onset of action of volatile agents depends on the blood:gas partition coefficient. A lower blood:gas partition coefficient and insolubility in blood means faster onset and offset of action. The blood gas coefficient for halothane is 2.4 while that of desflurane is 0.42. Desflurane is less soluble than halothane in blood. Halothane has a pungent smell that can irritate the airway which limits its use for a gaseous induction especially in paediatric anaesthesia. desflurane is not pungent.

Desfluranes boiling point is only slightly above normal room temperature (22.8°C) making it extremely volatile while the boiling point of halothane is approximately 50.2°C.

Number needed to treat can be defined as the number of patients who need to be treated to prevent one additional bad outcome.

It can be found as:

NNT=1/Absolute Risk Reduction (rounded to the next integer since number of patients can be integer only).

where ARR= (Risk factor associated with the new drug group) — (Risk factor associated with the currently available drug)

So,

ARR= (43.9-37.3)

ARR= 6.6

NNT= 1000/6.6

NNT=151.5

The data is ideal for chi square test evaluation as it will help determine if observed outcomes are in line with expected outcomes, and also if results are significant or due to chance.

The student’s t test is not ideal as it requires comparison of means from different populations, rather than proportions.

Pearson’s coefficient of linear regression is not ideal as it requires the plotting of a linear regression.

The numbers should be analysed before determining if there are any statistical conclusions that can be drawn from the population.

Statistical analysis is always required to determine the performance of any treatment during a clinical drug trial. Conclusions cannot be drawn simply by looking at the data.

The blood vessel well is divided into 3 parts, namely:

The tunica intima, which is the deepest layer. It contains endothelial cells separated by gap junctions

The tunica media, primarily consisting of the involuntary smooth muscle fibres, laid out in spiral layers with elastic fibres and connective tissue.

The tunica adventitia, which is the most superficial layer. It consists of the vasa vasorum, fibroblast and collagen.

Every surgical procedure is associated with a stress response which comprises a number of endocrine, metabolic, and immunological changes triggered by neuronal activation of the hypothalamic-pituitary-adrenal axis. The overall metabolic effect of the stress response to surgery includes an increase in secretion of catabolic hormones, such as cortisol and catecholamine, and a decrease in secretion of anabolic hormones, such as insulin and testosterone. The increase in levels of catabolic hormones in plasma stimulates glucose production, and there is a relative lack of insulin together with impaired tissue insulin sensitivity and glucose utilization, which is called insulin resistance. Consequently, blood glucose concentrations will increase, even in the absence of pre-existing diabetes.

A study compared the effects of spinal and general anaesthesia on changes in blood glucose concentrations during surgery in nondiabetic patients. Although mean blood glucose concentrations showed a significant proportional increase during surgery in both groups, this effect was much more significant with general anaesthesia than with spinal anaesthesia. These results indicate that spinal anaesthesia is more effective than general anaesthesia in attenuating the hyperglycaemic response to surgery.

The correlation coefficient gives us the idea about relation between two parameters. i.e. to what extent change in parameter A could prompt a change in parameter B. The numerical value of correlation coefficient could not be greater than 1.

The first rib is an atypical rib. It is short, wide, and flattened and lies in an oblique plane.

It has a small scalene tubercle on its medial border which marks the point of attachment of scalenus anterior. The lower surface lies on the pleura and is smooth.

The tubercle on the upper surface separates an anterior groove for the subclavian vein and a posterior groove for the subclavian artery and lower trunk of the brachial plexus.

Scalenus medius is attached to a roughened area posterior to the groove for the subclavian artery.

The upper surface gives attachment anteriorly to the subclavius muscle and costoclavicular ligament.

Pipeline gases (in the UK this includes: Oxygen, Nitrous oxide, Medical air, and Entonox) are supplied at 4 bar (or 400 kPa), and compressed air is supplied at 7 bar for power tools.

Carbon dioxide and nitric oxide are usually only supplied in cylinders.

Ketamine is usually used as a racemic mixture, i.e. (R/S)-ketamine. For over 20 years, use of the more potent (S)-enantiomer by anaesthesiologists has become a preferred option due to the assumption of increased anaesthetic and analgesic properties, a more suitable control of anaesthesia, and of an improved recovery from anaesthesia.

The use of ketamine in anaesthesia and psychiatry may be accompanied by the manifestation of somatic and especially psychomimetic symptoms such as perceptual disturbances, experiences of dissociation, euphoria, and anxiety.

Total body water (TBW) is about 50% to 70% in adults depending on how much fat is present. ECF is relatively contracted in an obese person.

The simple rule is 60-40-20. (60% of weight = total body water, 40% of body weight is ICF and 20% is ECF)

For this woman, the total body water is 36 litres (0.6 × 60). ECF is 12 litres (1/3 of TBW) and 24 litres (2/3 of TBW) is intracellular fluid .

Sodium concentration is approximately 135-145 mmol/L in the ECF.

The ECF is made up of both intravascular and extravascular fluid and plasma proteins is found in both.

Cardiac output = stroke volume x heart rate

Left ventricular ejection fraction = (stroke volume / end diastolic LV volume ) x 100%

Stroke volume = end diastolic LV volume – end systolic LV volume

Pulse pressure = Systolic Pressure – Diastolic Pressure

Systemic vascular resistance = mean arterial pressure / cardiac output
Factors that increase pulse pressure include:
-a less compliant aorta (this tends to occur with advancing age)
-increased stroke volume

The National Institute for Health and Care Excellence (NICE) has published guidelines on infective endocarditis prophylaxis (IE). The goal was to create clear guidelines for antibiotic prophylaxis in patients undergoing dental procedures as well as certain non-dental interventional procedures. A number of studies have found an inconsistent link between recent interventional procedures and the development of infective endocarditis in both dental and non-dental procedures.

Antibiotic prophylaxis against infective endocarditis is not advised or required in the following situations:

Dental patients undergoing procedures
Patients undergoing procedures involving the upper and lower gastrointestinal tracts, the genitourinary tract (including urological, gynaecological, and obstetric procedures, as well as childbirth), and the upper and lower respiratory tract (including ear, nose and throat procedures and bronchoscopy).

Antibiotic resistance can be exacerbated by the indiscriminate use of prophylactic antibiotics, but this is not the primary reason for avoiding their use in these situations.

To reduce the risk of endocarditis, any patient who is at risk of developing IE should be investigated and treated as soon as possible. Patients with the following conditions are at risk of developing IE:
acquired valvular heart disease with regurgitation or stenosis
previous valve replacement
structural congenital heart disease
past history of IE, or
hypertrophic cardiomyopathy (HOCM)

It would also be appropriate for high-risk dental procedures and those with severe gingival disease.

Although this patient may not have structural heart disease, ABs should be administered on a case-by-case basis.

The diaphragm divides the thoracic cavity from the abdominal cavity. Structures penetrate the diaphragm at different vertebral levels through openings in the diaphragm to communicate between the two cavities. The diaphragm has openings at three vertebral levels:

T8: vena cava, terminal branches of the right phrenic nerve
T10: oesophagus, vagal trunks, left anterior phrenic vessels, oesophageal branches of the left gastric vessels
T12: descending aorta, thoracic duct, azygous and hemi-azygous vein.

Pituitary tumours that compress the optic chiasma primarily affect the neurones that decussate at this location. Bitemporal hemianopia is caused by neurones that emerge from the nasal half of the retina and transmit the temporal half of the visual field.

The axons of ganglion cells in the retina form the optic nerve.

It exits the orbit through the optic foramen and projects to the thalamic lateral geniculate body. The optic chiasma forms above the sella turcica as the nasal fibres decussate along the way. The optic radiation travels from the lateral geniculate body to the occipital cortex.

Lesions at various points along this pathway cause the following visual field defects:

Scotoma implies partial retinal or optic nerve damage.
Monocular vision loss occurs when the optic nerve is completely damaged.
Pathology at the optic chiasma causes bitemporal hemianopia.
Cortical blindness with occipital cortex pathology and homonymous hemianopia with lesions compromising the optic radiation.

Two bonded wires of dissimilar metals, iron/constantan or copper/constantan, make up a thermocouple (constantan is an alloy of copper and nickel). At the tip, a thermojunction voltage is generated that is proportional to temperature (Seebeck effect).

All of the other connections are non-linear.

For a single compartment model, the relationship between a decrease in plasma concentration of an intravenous bolus of a drug and time is a washout exponential.

A sine wave is the relationship between current and degrees or time from a mains power source.

A sigmoid curve represents the relationship between efficacy and log-dose of a pure agonist on mu receptors.

The pressure of a fixed mass of gas and its volume (Boyle’s law) at a fixed temperature are inversely proportional, resulting in a hyperbolic curve.

The fibrotendinous ring formed by the congregation of the rectus muscles at the apex of the orbit does not include superior oblique. This muscle is completely outside the ring and so it is the most difficult muscle to anaesthetise completely. A good grasp of the anatomy of the area being anaesthetised is important with all regional anaesthetic techniques so that potential problems and complications with a block can be anticipated.

The borders of this pyramid whose apex points upwards and outwards of the bony orbit are as follows:
Floor – Zygoma and Maxilla
Roof – frontal bone
Medial wall – maxilla, ethmoid, sphenoid and lacrimal bones.
Lateral wall – greater wing of the sphenoid and the zygoma.

The four recti muscles (superior, medial, lateral and inferior) originate from a tendinous ring (the annulus of Zinn) and extend anteriorly to insert beyond the equator of the globe. Bands of connective tissue are present between the rectus muscles forming a conical structure and hinder the passage of local anaesthetic.

The superior oblique muscle is situated outside this ring and is the most difficult muscle to anaesthetise completely, particularly with a single inferotemporal peribulbar injection. An additional medial injection may help to prevent this.

The cranial nerve supply to the extraocular muscles are:
3rd (inferior oblique, inferior recti, medial and superior)
4th (superior oblique), and
6th (lateral rectus).

The long and short ciliary nerves provide the sensory supply to the globe and these are branches of the nasociliary nerve, (which is itself a branch of the ophthalmic division of the trigeminal nerve).

To achieve anaesthesia for the eye, these nerves which enter the fibrotendinous ring need to be fully blocked to anaesthetise the eye for surgery.

Multiple regression analysis revealed that velocity of lactate accumulation (VOBLA) accounted for 92 percent of the variation in marathon running velocity (VM), and VOBLA plus training volume prior to the marathon accounted for 96 percent of the variation. Percent ST muscle fibre distribution (r = 0.55-0.69) and capillary density (r = 052-0.63) were found to be positively correlated with all performance variables. As a result, marathon running performance was linked to VOBLA and the ability to run at a pace close to it during the race. The percent ST, capillary density, and training volume were all related to these properties.

Another metabolic adaptation compared to normal people is the early selection of fat for oxidation by muscle, especially when glucose availability is limited during high-intensity exercise. This helps to delay the onset of muscle fatigue, but it does not prevent VOBLA.

For a given level of exercise, training can also result in cardiovascular adaptation, such as increased heart size, increased contractility, and a slower heart rate. All of these factors contribute to an increase in maximal oxygen consumption (VO2 max), but genetic factors, despite intensive training, play a large role in an athlete’s performance.

The neuromuscular blocking agent is likely to be filtered and not reabsorbed by the renal tubules due to an exclusion process.

Neuromuscular blocking agents that contain one or more quaternary nitrogen atoms are polar and ionised. As a result, the molecules have low lipid solubility, low membrane diffusion capacity, and low distribution volume.

It’s unlikely that a compound with three quaternary nitrogen atoms is an ester. Its high polarity would prevent molecules from moving quickly into tissues.

When drugs have a low hepatic extraction ratio (0.3), the venous and arterial drug concentrations are nearly identical. The liver is not the primary site of drug metabolism.

Therefore:

Changes in liver blood flow have no effect on clearance.
Protein binding, intrinsic metabolism, and excretion are all very sensitive to changes in clearance.
When taken orally, there is no first-pass metabolism.

There is no reason for the lungs to eliminate any neuromuscular blocking agent.

According to European Group protocol for the investigation of MH susceptibility, muscle biopsy should be performed on quadriceps muscle (either vastus medialis or vastus lateralis), using regional anaesthesia (avoiding local anaesthetic infiltration) or general anaesthetic techniques. Local anaesthetic solution within muscle fibres may affect in vitro contraction testing.

Desflurane is a weak triggering anaesthetic of malignant hyperthermia so is avoided in MH susceptible patients. This includes all volatile inhalational agents and suxamethonium.

General anaesthetic with the volatile free anaesthetic machine may be considered but spinal anaesthesia is a better choice due to the possibility of airway problems.

The maximum safe amount of bupivacaine is 2mg/kg. Addition of adrenaline slows down absorption of the local anaesthetic and allows a maximum dose of 2.5mg/kg to be used.

The maximum safe dose of bupivacaine for this patient is 125 mg.

A 0.125% solution will contain 0.125g/100mL or 125mg/100 mL.

The maximum volume of local anaesthetic is approximately 80-100 mL.

Staphylococcus aureus infection is the most likely cause.

Surgical site infections (SSI) occur when there is a breach in tissue surfaces and allow normal commensals and other pathogens to initiate infection. They are a major cause of morbidity and mortality.

SSI comprise up to 20% of healthcare associated infections and approximately 5% of patients undergoing surgery will develop an SSI as a result.
The organisms are usually derived from the patient’s own body.

Measures that may increase the risk of SSI include:
-Shaving the wound using a single use electrical razor with a disposable head
-Using a non iodine impregnated surgical drape if one is needed
-Tissue hypoxia
-Delayed prophylactic antibiotics administration in tourniquet surgery, patients with a prosthesis or valve, in clean-contaminated surgery of in contaminated surgery.

Measures that may decrease the risk of SSI include:
1. Intraoperatively
– Prepare the skin with alcoholic chlorhexidine (Lowest incidence of SSI)
-Cover surgical site with dressing

In contrast to previous individual RCT’s, a recent meta analysis has confirmed that administration of supplementary oxygen does not reduce the risk of wound infection and wound edge protectors do not appear to confer benefit.

2. Post operatively
Tissue viability advice for management of surgical wounds healing by secondary intention

Use of diathermy for skin incisions
In the NICE guidelines the use of diathermy for skin incisions is not advocated. Several randomised controlled trials have been undertaken and demonstrated no increase in risk of SSI when diathermy is used.

The ventilatory anaerobic threshold (VAT), formerly referred to as the anaerobic threshold, is an index used to estimate exercise capacity. During the initial (aerobic) phase of CPET, which lasts until 50€“60% of Vo2max is reached, expired ventilation (VE) increases linearly with Vo2 and reflects aerobically produced CO2 in the muscles. Blood lactate levels do not change substantially during this phase, since muscle lactic acid production is minimal.

During the latter half of exercise, anaerobic metabolism occurs because oxygen supply cannot keep up with the increasing metabolic requirements of exercising muscles. At this time, there is a significant increase in lactic acid production in the muscles and in the blood lactate concentration. The Vo2 at the onset of blood lactate accumulation is called the lactate threshold or the VAT. The VAT is also defined as the point at which minute ventilation increases disproportionately relative to Vo2, a response that is generally seen at 60€“70% of Vo2max.

The VAT is a useful measure as work below this level encompasses most daily living activities. The ability to achieve the VAT can help distinguish cardiac and non€�cardiac (pulmonary or musculoskeletal) causes of exercise limitation, since patients who fatigue before reaching VAT are likely to have a non€�cardiac problem.

When VAT is detected, patients with PVo2 of ©½10€…ml/kg/min have a high event rate.

The oesophagus is a muscular tube that connects the pharynx to the stomach. It begins at the lower border of the cricoid cartilage and C6 vertebra. It ends at T11.

The oesophagus has physiological constrictions at the following levels:
1. Cervical constriction: Pharyngo-oesophageal junction (15 cm from the incisor teeth) produced by the cricopharyngeal part of the inferior pharyngeal constrictor muscle
2. Thoracic constrictions:
i. where the oesophagus is first crossed by the arch of the aorta (22.5 cm from the incisor teeth)
ii. where the oesophagus is crossed by the left main bronchus (27.5 cm from the incisor teeth)
3. Diaphragmatic constriction: where the oesophagus passes through the oesophageal hiatus of the diaphragm (40 cm from the incisor teeth)

Awareness of these constrictions is important for clinical purposes when it is required to pass instruments through the oesophagus into the stomach or when viewing radiographs of patients’ oesophagus.

The hazard ratio (HR) is simply a comparison of two hazards in a study. It provides an estimate of the ratio of the hazard rates between the experimental group and a control group over the entire study duration. It is typically used when analysing survival over time, hence is the most suitable statistical method in this case.

An odds ratio is a statistic that quantifies the strength of the association between two events, A and B. It is the €œmeasure of association€� for a case-control study.

The Pearson product-moment correlation coefficient (Pearson’s correlation, for short) is a measure of the strength and direction of association that exists between two variables. An example would be if scientists wanted to evaluate the relationship between quality of certain population of rice and their genetic make-up.

Relative risk is the ratio of the risks for an event for the exposure group to the risks for the non-exposure group. Thus relative risk provides an increase or decrease in the likelihood of an event based on some exposure. Relative risk measures the association between the exposure and the outcome.

Absolute risk reduction is the number of percentage points your own risk goes down if you do a preventive act such as stop drinking alcohol. It depends on what your risk factors are to begin with.

The mandibular branch of the trigeminal nerve passes through the foramen ovale. Other structures that pass through this foramen are the accessory meningeal artery, and occasionally, the lesser petrosal nerve.

These are the structures that pass through the other openings in the cranial fossa:

Foramen rotundum – Maxillary branch of the trigeminal nerve

Foramen lacerum – Greater petrosal nerve, traversed by the internal carotid artery

Superior orbital fissure – Oculomotor nerve; trochlear nerve; lacrimal, frontal and nasociliary branches of the ophthalmic branch of the trigeminal nerve; abducens nerve, superior ophthalmic vein

Stylomastoid foramen – facial nerve.

Drug interactions can be seen in the following examples:

Additive interaction (summation).

Additive effects are described for intravenous drug combinations such as ketamine and thiopentone or ketamine and midazolam. Different mechanisms of action are used by them. Thiopentone and midazolam are GABAA receptor agonists, whereas ketamine is an NMDA receptor antagonist. Nitrous oxide and halothane are two other examples.

Synergism is a supra-additive interaction.

Refers to the administration of two drugs with similar pharmacological properties and closely related sites of action, resulting in a combined effect that is greater than the sum of the contributions of each component. The construction of an isobologram can be used to interpret and understand these. The best example is the hypnotic effect of benzodiazepines and intravenous induction agents like propofol. As part of a co-induction technique, midazolam is frequently given before propofol.

Potentiation

In a dose-dependent manner, volatile agents enhance the effects of neuromuscular blocking agents. Electrolyte disturbance (hypomagnesaemia), Penicillin, and probenecid can all increase the effects of neuromuscular blocking agents (the latter has no similar pharmacological activity).

Infra-additive interaction (antagonism).

This can be subdivided into the following categories:

-Pharmacokinetic interference occurs when one drug affects the absorption of another through the gastrointestinal tract or when hepatic microsomal enzyme induction influences metabolism.
-Heparin and protamine, for example, or heavy metals and chelating agents, are examples of chemical antagonists.
-Competitive reversible antagonistic antagonism of receptors, such as opioids and naloxone, and irreversible antagonistic antagonism of receptors

Electrical resistivity is a measure of a material’s property to oppose the flow of electric current. This is expressed in Ohm-meters (Ω‹…m). The symbol of resistivity is usually the Greek letter Ï� (rho). A high resistivity means that a material does not conduct electric charge well.

Electrical resistivity is defined as the relation between the electric field inside a material, and the electric current through it as a consequence:

� = E/J

in which Ï� is the resistivity of the material (Ω‹…m),
E is the magnitude of the electrical field in the material (V/m),
J is the magnitude of the electric current density in the material (A/m2)

If the electric field (E) through a material is very large and the flow of current (J) is very small, it means that the material has a high resistivity.

Tests are used to confirm the presence of a particular disease. However the results can be misleading at times since most of the tests have some limitations associated with them.
Sensitivity is the correct term that refers to the probability of a positive test. The others are explained below:

False Positive rates refer to the proportion of the patients who don’t have the condition being detected as positive.

False Negative rates refer to the proportion of the patients who have the condition being detected as negative (like the 20% of the patients that went undetected by the Ca-125 test).

Specificity describes the ability of a test to detect and pick up people without the disease. Absolute risk ratio compares the rate of two separate outcomes.

The Drager Oxylog® 1000 is a pneumatically powered, time-dependent, volume-titrated emergency ventilator with a pressure limit. It is compatible with CD cylinder oxygen. The CD cylinder is a strong and lightweight cylinder usually composed of aluminium or Kevlar. The internal cylinder volume is 2 litres, and the pressure of a full cylinder is 230 bar. The volume of the full cylinder is determined by applying Boyle’s law: P1 × V1 = P2 × V2

Where:
P1= pressure of a full cylinder (230 bar)
V1= volume of oxygen at that pressure (2 litres)
P2= final pressure (1 bar), and
V2= volume of oxygen in the full cylinder.

Substituting values into the equation:

230 × 2 = 1 x V2
V2 = 460 litres. The flow of fresh gas is 4 litres/minute + 1 litre/minute required by the control, making a total of 5 litres/minute. The amount of time it takes for the cylinder to empty would be the total volume of oxygen in the full cylinder divided by the amount of oxygen expelled per minute: 460/5 = 92, meaning it would take 92 minutes for the cylinder to empty.

When there is a fall in ionised plasma calcium levels, the chief cells of the parathyroid glands are stimulated to secrete parathyroid hormone (PTH).

50% of extracellular calcium occurs as non-ionised, protein- (albumin-)bound calcium.

The degree of ionisation increases with low ph and decreases with high pH.

There is increased renal calcium excretion with secretion of calcitonin.