The measure of drug potency or therapeutic response is the ED95. This is defined as the dose of a neuromuscular blocking drug required to produce a 95% depression of muscle twitch height. The ED50 and ED90 describe a depression of twitch height by 50% and 90% respectively.

The ED95 (mg/kg) of the commonly used neuromuscular blocking agents are:

suxamethonium: 0.27
rocuronium: 0.31
vecuronium: 0.04
pancuronium: 0.07
cisatracurium: 0.04
mivacurium: 0.08

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.

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.

Ampicillin belongs to the family of penicillin. Resistance to this group of drugs is due to ?-lactamase production which opens the ?-lactam ring and inactivates Penicillin G and some closely related congeners. The majority of Staphylococci and some strains of gonococci, B. subtilis, E. coli, and a few other bacteria produce penicillinase.

Resistance to cephalosporins is due to changes in penicillin-binding proteins.

Resistance to macrolides are due to post-transcriptional methylation of 23s bacterial ribosomal RNA

Resistance to fluoroquinolones is due to mutations in DNA gyrase.

Based on the presenting symptoms, this is the case of bacterial meningitis. The treatment of choice for bacterial meningitis is a cephalosporin. Cephalosporin acts by inhibiting bacterial cell wall synthesis.

With regards to the autonomic nervous system (ANS)

1. It is not under voluntary control
2. It uses reflex pathways and different to the somatic nervous system.
3. The hypothalamus is the central point of integration of the ANS. However, the gut can coordinate some secretions and information from the baroreceptors which are processed in the medulla.

With regards to the central nervous system (CNS)
1. There are myelinated preganglionic fibres which lead to the
ganglion where the nerve cell bodies of the non-myelinated post ganglionic nerves are organised.
2. From the ganglion, the post ganglionic nerves then lead on to the innervated organ.

Most organs are under control of both systems although one system normally predominates.

The nerves of the sympathetic nervous system (SNS) originate from the lateral horns of the spinal cord, pass into the anterior primary rami and then pass via the white rami communicates into the ganglia from T1-L2.

There are short pre-ganglionic and long post ganglionic fibres.
Pre-ganglionic synapses use acetylcholine (ACh) as a neurotransmitter on nicotinic receptors.
Post ganglionic synapses uses adrenoceptors with norepinephrine / epinephrine as the neurotransmitter.
However, in sweat glands, piloerector muscles and few blood vessels, ACh is still used as a neurotransmitter with nicotinic receptors.

The ganglia form the sympathetic trunk – this is a collection of nerves that begin at the base of the skull and travel 2-3 cm lateral to the vertebrae, extending to the coccyx.

There are cervical, thoracic, lumbar and sacral ganglia and visceral sympathetic innervation is by cardiac, coeliac and hypogastric plexi.

Juxta glomerular apparatus, piloerector muscles and adipose tissue are all organs under sole sympathetic control.

The PNS has a craniosacral outflow. It causes reduced arousal and cardiovascular stimulation and increases visceral activity.

The cranial outflow consists of
1. The oculomotor nerve (CN III) to the eye via the ciliary ganglion,
2. Facial nerve (CN VII) to the submandibular, sublingual and lacrimal glands via the pterygopalatine and submandibular ganglions
3. Glossopharyngeal (CN IX) to lungs, larynx and tracheobronchial tree via otic ganglion
4. The vagus nerve (CN X), the largest contributor and carries ¾ of fibres covering innervation of the heart, lungs, larynx, tracheobronchial tree parotid gland and proximal gut to the splenic flexure, liver and pancreas

The sacral outflow (S2 to S4) innervates the bladder, distal gut and genitalia.

The PNS has long preganglionic and short post ganglionic fibres.
Preganglionic synapses, like in the SNS, use ACh as the neuro transmitter with nicotinic receptors.
Post ganglionic synapses also use ACh as the neurotransmitter but have muscarinic receptors.

Different types of these muscarinic receptors are present in different organs:
There are:
M1 = pupillary constriction, gastric acid secretion stimulation
M2 = inhibition of cardiac stimulation
M3 = visceral vasodilation, coronary artery constriction, increased secretions in salivary, lacrimal glands and pancreas
M4 = brain and adrenal medulla
M5 = brain

The lacrimal glands are solely under parasympathetic control.

Iliacus, and Psoas major are the most important muscles that produce flexion at the hip.

They are collectively called the iliopsoas muscle. The iliacus muscle originates from the ilium while the psoas major muscle takes its origin from the lumbar vertebrae and sacrum. Their insertion is the lesser trochanter of the femur. They work together to produce flexion and external rotation of the hip. The nerve supply is from branches of the lumbar plexus (L1, 2, 3) femoral nerve (L2, 3, 4) and short direct muscular branches (T12, L1, L2, L3 and L4).

Sartorius, Rectus femoris, Tensor fasciae latae, and Pectineus muscles are two-joint muscles acting at the knee and having less influence on hip flexion:

Rectus femoris and sartorius are involved in extension of the knee. They are supplied by branches of the femoral nerve.

Myotomes associated with key movement of the lower limb are:

L1/L2 – Hip flexion
L2/L3/L4 – Hip adduction, quadriceps (knee extension)
L4/L5 – Hip abduction
L5 – Great toe dorsiflexion.

Since knee extension is not affected, L2, L3 and L4 are still intact.

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 tenth cranial nerve (vagus nerve) has both sensory and motor divisions.

It emerges from the anterolateral surface of the medulla in a groove between the olive and the inferior cerebellar peduncle as a series of 8-10 rootlets . It leaves the skull through the middle compartment of the jugular foramen and descends within the carotid sheath between the internal carotid artery and internal jugular vein. The right vagus crosses in front of the first part of the subclavian artery. It gives off the right recurrent laryngeal nerve at this point.

The left recurrent laryngeal nerve passes around the ligamentum arteriosum.

The external laryngeal nerve supplies the cricothyroid muscle while the recurrent laryngeal nerve supplies the other laryngeal muscles.

The cranial part of the accessory nerve supplies all the muscles of the palate, via the pharyngeal plexus and the pharyngeal branch of the vagus nerve, except the tensor veli palatini which is supplied by the mandibular branch of the trigeminal nerve.

The Sternothyroid, Sternohyoid, and Omohyoid muscles are supplied by the ansa cervicalis while the thyrohyoid muscle is supplied by the hypoglossal nerve.

During fetal development, blood oxygenated by the placenta flows to the foetus through the umbilical vein, bypasses the fetal liver through the ductus venosus, and returns to the fetal heart through the inferior vena cava.

Blood returning from the inferior vena cava then enters the right atrium and is preferentially shunted to the left atrium through the patent foramen ovale. Blood in the left atrium is then pumped from the left ventricle to the aorta. The oxygenated blood ejected through the ascending aorta is preferentially directed to the fetal coronary and cerebral circulations.

Deoxygenated blood returns from the superior vena cava to the right atrium and ventricle to be pumped into the pulmonary artery. Fetal pulmonary vascular resistance (PVR), however, is higher than fetal systemic vascular resistance (SVR); this forces deoxygenated blood to mostly bypass the fetal lungs. This poorly oxygenated blood enters the aorta through the patent ductus arteriosus and mixes with the well-oxygenated blood in the descending aorta. The mixed blood in the descending aorta then returns to the placenta for oxygenation through the two umbilical arteries.

Alpha 1 adrenergic receptor stimulation results in vasoconstriction of peripheral arteries mainly of those of skin, gut and kidney arterioles. This would cause and increase in total peripheral resistance and mean arterial pressure and as a result the perfusion of vital organs i.e. brain, heart and lungs are maintained.

Muscarinic M2 receptor also known as cholinergic receptor are located in heart, where they act to slow the heart rate down to normal sinus rhythm after negative stimulatory actions of parasympathetic nervous system. They also reduce contractile forces of the atrial cardiac muscle, and reduce conduction velocity of AV node. This could worsen the compensation.

Stimulation of beta 2 adrenergic receptor result in dilation of smooth muscle as in bronchodilation.

Beta 3 adrenergic receptors are present on cell surface f both white and brown adipocytes and are responsible for lipolysis, thermogenesis, and relaxation of intestinal smooth muscle.

Alpha 2 adrenergic receptor stimulation results in inhibition of the release of noradrenaline in a form of negative feedback.

The external laryngeal nerve arises from the superior laryngeal nerve and provides innervation to the cricothyroid muscle.

The other muscles mentioned receive their innervations from the recurrent laryngeal nerve.

Bell’s palsy is facial muscle weakness or paralysis that arises from idiopathic damage to the facial nerve. It can occur at any age but is commonly associated with some conditions:
1. pregnancy
2. diabetes
3. upper respiratory ailment
4. GBS
5. Toxins

The common symptoms of Bell’s palsy are:
1. Abnormal corneal reflex as the facial nerve controls the motor aspect of the corneal reflex.
2. The loss of control of facial muscles and eyelids leads to decreased tear production.
3. mild weakness to total paralysis on one side of the face, occurring within hours to days.
4. Bell’s palsy is a lower motor neuron lesion that usually spares the forehead while the upper motor near lesions, like stroke, involves the entire face.
5. The anterior two-thirds of the tongue is supplied by the chorda tympani branch of the facial nerve, thus resulting in loss of taste.
6. Ptosis can be a feature of Bell’s palsy but Bell’s palsy would typically show unilateral symptoms rather than bilateral.

A prospective randomised double blind controlled trial against cyclizine in multiple centres is the most likely to change your practice.

Case controlled studies are efficient in identifying an association between a drug treatment and outcome and are usually conducted retrospectively. They are generally less valued than prospective randomised trials. They cannot generate incidence data, are subject to bias, have difficult selection of controls and can be made more difficult if note keeping is not reliable.

The gold standard in intervention-based studies is randomised controlled double blind trials. Its features are:

Treating all intervention groups identically
Reduction of bias by random allocation to intervention groups
Patients and researchers unaware of which treatment was given until at completion of study
Patients analysed within the group to which they were allocated, and
Analysis focused on estimating the size of the difference in predefined outcomes between intervention groups.

New healthcare interventions should be evaluated through properly designed randomised controlled trials (though there are some potential ethical disadvantages)

Conducting trials in multiple centres is an accepted way of evaluating a new drug as it may be the only way of recruiting sufficient number of patients within a reasonable time frame to satisfy the objectives of the trial. Type II statistical errors will occur if a small numbers of patients is used in study group.

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 adrenal medulla comprises chromaffin cells (pheochromocytes), which are functionally equivalent to postganglionic sympathetic neurons. They synthesize, store and release the catecholamines noradrenaline (norepinephrine) and adrenaline (epinephrine) into the venous sinusoids.
The majority of the chromaffin cells synthesize adrenaline.

Major surgery induces the systemic inflammatory response and this causes endothelial leakage and a low albumin level.

Albumin is a single polypeptide which is made but not stored in the liver. Therefore, levels are a reflection of synthetic activity. It is negatively charged and very soluble.

Only 40% of albumin is intravascular, and the rest in the in interstitial compartment.

If there was normal liver function during starvation, albumin will be maintained and proteolysis will occur elsewhere.
It is not catabolised during starvation.
Starvation and malnutrition may, however, present as part of other disease processes that are associated with hypalbuminaemia.

Causes of low albumin are

1. Decreased production (hepatic dysfunction)
2. Increased loss (renal dysfunction)
3. Redistribution (endothelial leak/damage)
4. Increased catabolism (very rare)

The patient is rebreathing carbon dioxide that has been exhaled.

Exhaustion of the soda lime and failure of the expiratory valve are the two most likely causes. A leak in the inspiratory limb is a less likely cause. Increased inhaled and exhaled carbon dioxide levels may appear with a normal-looking capnogram if the expiratory valve is ineffective.

The patient will exhale into both the inspiratory and expiratory limbs if the inspiratory valve is inoperable. A slanted downstroke inspiratory phase (as the patient inhales carbon dioxide-containing gas from the inspiratory limb) and increased end-tidal carbon dioxide can be seen on the capnogram.

Even if the soda lime were exhausted, a high fresh gas flow would be enough to prevent rebreathing. The difference in oxygen concentrations in inspired and expired breaths would be less pronounced.

Hypercapnia is caused by respiratory obstruction and malignant hyperthermia, but not by rebreathing.

99.7% of the values within 3 standard deviations of the mean.

For 99.7% confidence interval, you can find the range as follows:

1. Multiply the standard error by 3.

2. Subtract the answer from mean value to get the lower limit.

3. Add the answer obtained in step 1 from the mean value to get the upper limit.

For a confidence interval of 68%, multiply the standard error with 1 and repeat the process. For a 95% confidence interval, Standard Error is multiplied by 1.96 to get the interval.

Mesenteric ischemia is ischemia of the blood vessels of the intestines. It can be life-threatening, especially if the small intestine is involved.

The inferior mesenteric artery originates 3-4 cm above the bifurcation of the abdominal aorta.
The left colic artery branches off the inferior mesenteric artery to supply the following:
– distal 1/3 of the transverse colon
– descending colon

At approximately the left colic flexure (splenic flexure), a transition occurs in the blood supply of the GI tract. The SMA supplies the proximal part to the flexure, and the IMA supplies the part distal to the flexure. This is why the left colic flexure is a watershed area and is prone to ischemia exacerbated by atherosclerotic changes or hypotension. The dominant arterial supply of the splenic flexure is usually from the left colic artery, but it may also get collaterals from the left branch of the middle colic artery.

The AMA and PMA do not exist.
The splenic artery directly supplies the spleen and has branches that supply the stomach and the pancreas.
The proximal two-thirds of the transverse colon is supplied by the middle colic artery, a branch of the SMA.

Krebs’ cycle (tricarboxylic acid cycle or citric acid cycle) is a sequence of reactions in which acetyl coenzyme A (acetyl-CoA) is metabolised and this results in carbon dioxide and hydrogen atoms production.

This series of reactions occur in the mitochondria of eukaryotic cells, not the cytoplasm. The cycle requires oxygen and so, cannot function under anaerobic conditions.

It is the common pathway for carbohydrate, fat and some amino acids oxidation and is required for high energy phosphate bond formation in adenosine triphosphate (ATP).

When pyruvate enters the mitochondria, it is converted into acetyl-CoA. This represents the formation of a 2 carbon molecule from a 3 carbon molecule. There is loss of one CO2 but formation of one NADH molecule. Acetyl-CoA is condensed with oxaloacetate, the anion of a 4 carbon acid, to form citrate which is a 6 carbon molecule.

Citrate is then converted into isocitrate, alpha-ketoglutarate, succinyl-CoA, succinate, fumarate, malate and finally oxaloacetate.

The only 5 carbon molecule in the cycle is alpha-ketoglutarate.

The pH of CSF is 7.31 which is lower than plasma.

Compared to plasma, it has a lower concentration of potassium, calcium, and protein and a higher concentration of sodium, chloride, bicarbonate and magnesium.

CSF usually has no cells present but if white cells are present, there should be no more than 4/ml.

The pressure of CSF should be less than 20 cm of water.

The concentration of glucose is approximately two-thirds of that of plasma, and it has a concentration of approximately 3.3-4 mmol/L.

In the Child-Pugh classification system, the following 5 components are determined or calculated in order:

Ascites

Grade of encephalopathy

Serum bilirubin (?mol/L)

Serum Albumin (g/L)

Prothrombin time or INR

Raised liver enzymes are not the component of the classification system.

The cylindrical structure(spine), starts from the foramen magnum in medulla oblongata at the skull’s base. Its length varies in gender with men having 45cm and women having up to 43 cm. The spine contains 31 pairs of spinal nerves, named according to the spinal region:
– 8 cervical nerve pairs ( C1-C8)
– 12 thoracic nerve pairs ( T1-T12)
– 5 lumbar nerve pairs (L1-L5)
– 5 sacral nerves (S1-S5) and
– 1 coccygeal nerve pair.
These spinal nerves are classified as the peripheral nervous system though they branch from the spinal cord and central nervous system. They interact directly with the spinal cord to modulate the motor and sensory information from the peripheral’s region. As the nerves emerges form the spinal cords they are known as rootlets. They join to form nerve roots, and depending on their position, we have anterior nerve roots and posterior.

The spinal cord is supplied by two posterior and one anterior spinal arteries which anastomoses caudally, at the conus medullaris.

The anterior spinal artery supplies the anterior two-thirds of the spinal cord and medulla. Disruption of the anterior spinal artery supply is characterised by ischaemia or infarction of motor tracts (corticospinal) and loss of pain and temperature sensation below the level of the lesion.

The posterior spinal arteries supply the posterior columns (posterior third of the spinal cord). Infarction of the posterior columns results in the loss of proprioceptive, vibration and two-point discrimination.

The spinal cord normally ends at the level of L1 or L2 in an adult and L3 in a newborn.

The most likely of the differential diagnosis in this case is a duodenal ulcer located on the posterior abdominal wall.

These can cause an erosion of the abdominal wall, eventually affecting the gastroduodenal artery and resulting in major bleeding and haematemesis.

Gastroduodenal artery supplies the pylorus, proximal part of the duodenum, and indirectly to the pancreatic head (via the anterior and posterior superior pancreaticoduodenal arteries)

Anticholinergic agents are a group of drugs that blocks the action of the neurotransmitter called acetylcholine at synapses in the central and peripheral nervous system.

Hyoscine, atropine, and glycopyrrolate are anticholinergic which acts at muscarinic receptors with little activity at the nicotinic receptors.

Hyoscine and atropine are naturally occurring esters. Since Glycopyrrolate is a synthetic quaternary amine, it does not cross the blood brain barrier. Noteworthy, hyoscine, butylbromide also does not cross the blood brain barrier significantly.

Prilocaine is the drug of choice for intravenous regional anaesthesia. 0.5% prilocaine (40 ml) is indicated for this condition.
Lidocaine is another alternative for this condition but volume and dose are likely to be inadequate for the procedure.

The following is the alveolar gas equation:

PAO2 = PiO2 − PaCO2/R

Where:

PAO2 is the partial pressure of oxygen in the alveoli.
PiO2 is the partial pressure of oxygen inhaled.
PaCO2 stands for partial pressure of carbon dioxide in the arteries.
The amount of carbon dioxide produced (200 mL/minute) divided by the amount of oxygen consumed (250 mL/minute) equals R = respiratory quotient. With a normal diet, the value is 0.8.

By subtracting the partial pressure exerted by water vapour at body temperature, the PiO2 can be calculated:

PiO2 = 0.21 × (100 kPa − 6.3 kPa)
PiO2 = 19.8

Substituting:
PAO2 = 19.8 − 10/0.8
PAO2 = 19.8 − 12.5
PAO2 = 7.3k Pa

A preplanned preinduction strategy includes the consideration of various interventions designed to facilitate intubation should a difficult airway occur. Non-invasive interventions intended to manage a difficult airway include, but are not limited to: (1) awake intubation, (2) video-assisted laryngoscopy, (3) intubating stylets or tube-changers, (4) SGA for ventilation (e.g., LMA, laryngeal tube), (5) SGA for intubation (e.g., ILMA), (6) rigid laryngoscopic blades of varying design and size, (7) fibreoptic-guided intubation, and (8) lighted stylets or light wands.

Most supraglottic airway devices (SADs) are designed for use during routine anaesthesia, but there are other roles such as airway rescue after failed tracheal intubation, use as a conduit to facilitate tracheal intubation and use by primary responders at cardiac arrest or other out-of-hospital emergencies. Supraglottic airway devices are intrinsically more invasive than use of a facemask for anaesthesia, but less invasive than tracheal intubation. Supraglottic airway devices can usefully be classified as first and second generation SADs and also according to whether they are specifically designed to facilitate tracheal intubation. First generation devices are simply ‘airway tubes’, whereas second generation devices incorporate specific design features to improve safety by protecting against regurgitation and aspiration.