Adrenaline is released by the adrenal glands, acts on ? 1 and 2, ? 1 and 2 receptors, and is responsible for fight or flight response.

It acts on ? 2 receptors in skeletal muscle vessels-causing vasodilation.

It acts on ? adrenergic receptors to inhibit insulin secretion by the pancreas. It also stimulates glycogenolysis in the liver and muscle, stimulates glycolysis in muscle.

It acts on ? adrenergic receptors to stimulate glucagon secretion in the pancreas
It also stimulates Adrenocorticotrophic Hormone (ACTH) and stimulates lipolysis by adipose tissue

The cephalic vein is a superficial vein that runs through the forearm and the arm, before draining into the axillary vein where it terminates.

Such a high rise of end-tidal CO2 (EtCO2) in a patient who is spontaneously breathing is often encountered.

Close observation should occur for further rises in EtCO2 and other signs of malignant hyperthermia. If this were to rise even more, it might be wise to ensure that ventilatory support is available.

A lot would depend on whether surgery was almost completed. At this stage of anaesthesia, it would be inappropriate to administer opioid antagonists or respiratory stimulants.

The relative risk (also known as risk ratio [RR]) is the ratio of risk of an event in one group (e.g., exposed group) versus the risk of the event in the other group (e.g., nonexposed group).

The odds ratio (OR) is the ratio of odds of an event in one group versus the odds of the event in the other group.

Hydrochloric acid is lost when you vomit for a long time (HCl). As a result, the following can be expected, in varying degrees of severity:

Hypokalaemia
Hypochloraemia
Increased bicarbonate to compensate for chloride loss and metabolic alkalosis

The alkalosis causes potassium to move from the intracellular to the extracellular compartment at first. Long-term vomiting and dehydration cause potassium to be excreted by the kidneys in order to conserve sodium. Dehydration can cause urea and creatinine levels to rise.

The actual base excess is always greater than the standard base excess.

The actual base excess (BE) is a measurement of a base’s contribution to a blood gas picture’s metabolic component. It’s the amount of base that needs to be added to a blood sample to bring the pH back to 7.4 after the respiratory component of a blood gas picture has been corrected (PaCO2 of 40 mmHg or 5.3 kPa). The BE has a normal range of +2 to 2. A large positive BE indicates a severe metabolic alkalosis, while a large negative BE indicates a severe metabolic acidosis. As a result, the actual BE in vitro is unaffected by CO2.

In vivo, however, standard BE is not independent of pCO2 because blood with haemoglobin acts as a better buffer than total ECF.

As a result, it is impossible to tell the difference between compensating for a respiratory disorder and compensating for the presence of a primary metabolic disorder.

The differences between in vitro and in vivo behaviour can be mostly eliminated if the BE is calculated for a haemoglobin concentration of 50 g/L (the ‘effective’ or virtual value of Hb if it was distributed throughout the extracellular space) rather than the actual haemoglobin. Because haemoglobin has a lower buffering capacity, the standard BE is higher than the actual BE. It reflects the BE better in the extracellular space rather than just the intravascular compartment.

Noradrenaline also called norepinephrine belongs to the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter.

They have sympathomimetic effects acting via adrenoceptors (?1, ?2,?1, ?2, ?3) or dopamine receptors (D1, D2).

May cause reflex bradycardia, reduce cardiac output and increase myocardial oxygen consumption

Cardiac conduction

Phase 0 – Rapid depolarization. Opening of fast sodium channels with large influx of sodium

Phase 1 – Rapid partial depolarization. Opening of potassium channels and efflux of potassium ions. Sodium channels close and influx of sodium ions stop

Phase 2 – Plateau phase with large influx of calcium ions. Offsets action of potassium channels. The absolute refractory period

Phase 3 – Repolarization due to potassium efflux after calcium channels close. Relative refractory period

Phase 4 – Repolarization continues as sodium/potassium pump restores the ionic gradient by pumping out 3 sodium ions in exchange for 2 potassium ions coming into the cell. Relative refractory period

Moderately high doses of dopamine produce a positive inotropic (direct?1 and D1 action + that due to Noradrenaline release), but the little chronotropic effect on the heart.

Vasoconstriction (?1 action) occurs only when large doses are infused.

At doses normally employed, it raises cardiac output and systolic BP with little effect on diastolic BP. It has practically no effect on nonvascular ? and ? receptors; does not penetrate the blood-brain barrier—no CNS effects.

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.

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= (165/1050)-(132/1044)

ARR= (0.157-0.126)

ARR= 0.031

NNT= 1/0.031

NNT=32.3

The liver receives blood supply from two sources.
1. Hepatic artery proper
It arises from the celiac trunk via the common hepatic artery and brings oxygenated blood to the liver.
It contributes to approximately 30% of the blood supply of the liver.
2. Hepatic portal vein – supplies the liver with partially deoxygenated blood, carrying nutrients absorbed from the small intestine. It gets tributaries from the inferior mesenteric vein, splenic vein, and superior mesenteric vein

The inferior mesenteric artery supplies the hindgut.
The superior mesenteric artery supplies the pancreas and intestine up to the proximal two-thirds of the transverse colon.
The inferior phrenic artery supplies the inferior surface of the diaphragm and oesophagus.

The Weibull distribution are used to describe various types of observed failures of the components. it is used in reliability and survival analysis.

Regression Analysis is used to measure the relationship between among two or more variable. It determines the effect of independent variables on the dependent variables.

Student t-test is one of the most commonly used method to test the hypothesis. It determines the significant difference between the means of two different groups.

A time series is a collection of observations of well-defined data obtained at regular interval of time.

Kaplan-Meier estimator is used to estimate the survival function from lifetime data. It can be derived from maximum likelihood estimation of hazard function. It is most likely used to measure the fraction of patient’s life for a certain amount of time after treatment.

The dose-response curve plots the graph of the dose (drug concentration) versus the response. As doses increase, the response increment diminishes; finally, doses may be reached at which no further increase in response can be achieved. This relation between drug concentration and effect is traditionally described by a hyperbolic curve. When the x-axis is plotted in log scale, the graph yields a sigmoid curve.

Efficacy (Emax) and potency (EC50) can be derived from this curve. Emax is the maximal effect achievable, with increasing concentration of a drug. EC50 is the concentration of the drug, wherein half of the maximal effect is achieved.

When the graph is plotted using a log [response/1-response] against log dose, the sigmoid curve becomes a straight line (Hill plot). A graph that transforms from a straight line to exponential curve is mathematically incorrect. A graph that transforms from either a wash-in or wash-out exponential curve to a straight line comes from an initial set of data plotted against time, to a logarithmic transformation of the initial data set against time.

The prostate is separated from the rectum by the Denonvilliers fascia (rectoprostatic fascia).

Waldeyers fascia functions to separate the rectum and the sacrum.

pH is the negative log to the base 10 of hydrogen ion concentration:

So, what power produces the answer?

pH = – log10 [H+]

Making [H+] the subject:

[H+] = 10-pH

Substituting, [H+] = 10-7

One nanomole = 1 x 10-9 or 0.000000001

10-7 = 1x 0.0000001 or 10 x 0.00000001 or 100 x 0.000000001

100 nanomole

Continuous closure of the vocal cords resulting in partial or complete airway obstruction is called Laryngospasm. It is a reflex that helps protect against pulmonary aspiration.

Predisposing factors include: Hyperactive airway disease, Insufficient depth of anaesthesia, Inexperience of the anaesthetist, Airway irritation, Smoking, Shared airway surgery and Paediatric patients

Its primary treatment includes checking for blood or stomach aspirate in the pharynx, removing any triggering stimulation, relieving any possible supra-glottic component to airway obstruction and application of CPAP with 100% oxygen.

In this patient, all the above has been done and the next treatment of choice is the administration of a rapidly acting intravenous anaesthetic agent such as propofol (0.5 mg/kg) in increments as it has been reported to relieve laryngospasm in approximately 75% of cases. Administering suxamethonium to an awake patient would be inappropriate at this stage.

Magnesium and lidocaine are used for prevention rather than acute treatment of laryngospasm. Superior laryngeal nerve blocks have been reported to successfully treat recurrent laryngospasm but it is not the next logical step in index patient.

Blood vessels (except capillaries and venules) have three distinctive layers (innermost to outermost):
1. Tunica intima
2. Tunica media
3. Tunica adventitia

The tunica media contains smooth muscle cells and is separated from the intima layer by the internal elastic lamina and the adventitia by the external elastic lamina.

The walls of the anterior nasal passage are supplied by the anterior ethmoidal branch of the nasociliary nerve, and the floor is innervated by the superior dental nerve (not the sphenopalatine nerves).

The walls and floor of the posterior nasal passage are innervated by the long and short sphenopalatine nerves and the great palatine nerve (not the superior dental nerves and the nasociliary nerve).

The vestibule is innervated by small branches of the infraorbital branch of the maxillary nerve.

The nasopharynx is innervated by the sensory branches of the trigeminal nerve (not the great palatine nerve).

Prostacyclin is a strong vasodilator. It is administered as an intravenous infusion for critical ischemia. Commercially, it is available as sodium epoprodtenol.

Atrial Natriuretic peptide (ANP) hormone secreted from the atria, kidney, and neural tissues. It primarily acts on renal vessel to maintain normal blood pressure and reduce plasma volume by: increasing the renal excretion of salt and water, glomerular filtration rate, vasodilation, and by increasing the vascular permeability. It also inhibits the release of renin and aldosterone.

Indoramin is an alpha-adrenoceptor blocking agent. which act selectively on post-synaptic-alpha adrenoreceptor, leading to decease in peripheral resistance.

Angiotensin II is a vasoconstrictor, causing high sodium retention. It also increases the secretion of antidiuretic hormone (ADH) and aldosterone level.

Randomisation allows for performance of experimental trials in a random order. Using this method gives us control over the confounding variables that are not supposed to be held constant.

For an instance, by employing randomisation we get to control biological differences among individual human beings during experimental trials.

Professor Mapleson classified non-rebreathing circuits based on the position of the APL valve, which controls fresh gas flow.

The Mapleson A (Magill) circuit is most effective in spontaneous breathing, requiring only 70-100 ml/kg (the patient’s minute volume) of fresh gas flow. The patient inhales fresh gas from the reservoir bag and tubing during inspiration. During expiration, the patient adds dead space gas (gas that hasn’t been exchanged) to the tubing and reservoir bag in addition to the fresh gas flow. At the patient’s end, alveolar gas is vented through the APL valve. During the expiratory pause, the fresh gas flow causes more gas to be released.

The Mapleson A is inefficient during controlled ventilation. Venting occurs during inspiration rather than during the expiratory phase, as it does during spontaneous ventilation. As a result, unless a high fresh gas flow of >20 L/minute is used, alveolar gas is rebreathed.

During spontaneous ventilation, the Mapleson D circuit is inefficient.

The oxygen concentration in a Hudson mask is insufficient to allow for adequate pre-oxygenation.

Always call for help early. This patient is at risk of gastro-oesophageal reflux, which is why a rapid sequence induction has been chosen. The patient is not pregnant, and the surgery is not urgent.

Plan A is to perform a rapid sequence induction under optimal conditions and secure the airway with a tracheal tube.

No more than three attempts with a direct laryngoscope (plus one attempt with a videolaryngoscope) should be made to intubate the trachea. Keep in mind that suxamethonium is wearing off. Ensuring adequate neuromuscular blockade at this stage is crucial; this might include administering a non-depolarizing relaxant if oxygenation can be maintained with bag-mask ventilation. Given the non-immediate nature of the surgery, there should be a low threshold to abandon intubation attempts and resort to Plan B.

An alternative strategy can then be planned.

The most important initial step is to declare a “failed intubation.” This will prevent further intubation attempts and alert your assistant that Plan A has failed. Maintaining oxygenation and anesthesia is also critical before implementing Plan B.

Do not administer another dose of suxamethonium. Insert a supraglottic airway if oxygenation fails and adequate ventilation cannot be maintained.

Plan D follows the declaration of a CICO (Cannot Intubate, Cannot Oxygenate) situation.

Respiratory inspiration causes a decreased pressure in the thoracic cavity, which in turn causes more blood to flow into the atrium.

Sitting up decreases venous because of the action of gravity on blood in the venous system.
Hypotension also decreases venous return.
A less compliant aorta, like in aortic stenosis increases end systolic left ventricular volume which decreases stroke volume.

Systemic vascular resistance = mean arterial pressure / cardiac output. Increased vascular resistance impedes the flow of blood back to the heart.

Increased venous return increases end diastolic LV volume as there is more blood returning to the ventricles.

Agonists activate the receptor as a direct result of binding to it with a characteristic affinity. Moreover, intrinsic activity of an agonist to its receptor determines the ability to create a maximal response.

Responses to low doses of a drug usually increase in direct proportion to dose. As doses increase, however, the response increment diminishes; finally, doses may be reached at which no further increase in response can be achieved. The relationship formed between the dose and response when plotted graphically is hyperbolic. This also shows that even at low receptor occupancy, a maximal response may be produced.

Antagonists bind to receptors in the same affinity as agonists, but they have no intrinsic efficacy. They do not activate generation of signal. Instead, they interfere with the ability of the agonist to activate the receptor.

Partial agonists are similar to full agonists in that they have similar affinity to the target receptor, but they produce a lower response than full agonists.

The degree of correlation is summarised by the correlation coefficient (r). This indicates how closely the points lie to a line drawn through the plotted data. In parametric data this is called Pearson’s correlation coefficient and can take any value between -1 to +1. A correlation of -1.0 indicates a perfect negative correlation, and a correlation of 1.0 indicates a perfect positive correlation.

For example

r = 1 – strong positive correlation (e.g. systolic blood pressure always increases with age)

r = 0 – no correlation (e.g. there is no correlation between systolic blood pressure and age)

r = – 1 – strong negative correlation (e.g. systolic blood pressure always decreases with age)

Whilst correlation coefficients give information about how one variable may increase or decrease as another variable increases they do not give information about how much the variable will change. They also do not provide information on cause and effect.

In contrast to the correlation coefficient, linear regression may be used to predict how much one variable changes when a second variable is changed.

The principal innervation of the small muscles of the hand is T1.

Superior vena cava is the main vein bringing blood back to the heart. It can get partially or completely blocked by various causes, the most common being due to malignant tumours of the mediastinum.

There are collateral pathways that form in long-standing cases with 60% or more stenosis and continue venous drainage in cases of superior vena obstruction. The collaterals are classified into four as follows:

1. The azygos-hemiazygos pathway
Azygos, hemiazygos, intercostal, and lumbar veins.

2. The internal and external mammary pathway
internal mammary, superior epigastric, and inferior epigastric veins and superficial veins of the thorax.

3. The lateral thoracic pathway
Lateral thoracic, thoracoepigastric, superficial circumflex, long saphenous, and femoral veins to collateralize to the IVC.

4. The vertebral pathway
Innominate, vertebral, intercostal, lumbar, and sacral veins to collateralize to the azygos and internal mammary pathways.

The neuroleptic malignant syndrome (NMS) is a rare complication in response to neuroleptic or antipsychotic medication.

The main features are:
– Elevated creatinine kinase
– Hyperthermia and tachycardia
– Altered mental state
– Increased white cell count
– Insidious onset over 1-3 days
– Extrapyramidal dysfunction (muscle rigidity, tremor, dystonia)
– Autonomic dysfunction (Labile blood pressure, sweating, salivation, urinary incontinence)

Management is supportive of ICU care, anticholinergic drugs, increasing dopaminergic activity with Amantadine, L-dopa, and dantrolene, and non- depolarising neuromuscular blockade drugs.

Since Olanzapine is a potential cause of NMS it is not a treatment.

Taste sensation from the anterior two-thirds of the tongue is carried by chorda tympani, a branch of the facial nerve.

The general somatic sensation of the anterior two-third of the tongue is supplied by the lingual nerve, a branch of the mandibular nerve.

Both general somatic sensation and taste from the posterior third of the tongue are carried by the glossopharyngeal nerve.

All the muscles of the tongue except palatoglossus are supplied by the hypoglossal nerve whereas palatoglossus is supplied by the vagus nerve. (This is because palatoglossus is the only tongue muscle derived from the fourth branchial arch)