The occlusion of the left anterior descending (LAD) coronary artery causes anterior ST elevation myocardial infarction (STEMI). It has the worst prognosis of all the infarct locations due to its larger infarct size. It has a higher rate of total mortality (27 percent versus 11 percent), heart failure (41 percent versus 15 percent), and a lower ejection fraction on admission than an inferior myocardial infarction (38 percent versus 55 percent ).

The LAD artery supplies the majority of the interventricular septum, as well as the anterior, lateral, and apical walls of the left ventricle, as well as the majority of the right and left bundle branches and the bicuspid valve’s anterior papillary muscle (left ventricle).

The left or right ventricle’s end-diastolic volume (EDV) is the volume of blood in each chamber at the end of diastole before systole. Preload is synonymous with the EDV.

120 mL is a typical left ventricular EDV (range 65-240 mL). The EDV of the right ventricle in a typical range is (100-160 mL).

With an ejection fraction (EF) of less than 45 percent, the patient is most likely suffering from systolic dysfunction. Increases in right and left ventricular end-diastolic pressures and volumes are likely with a reduced EF because the ventricles are not adequately emptied. The left atrium and the pulmonary vasculature are affected by the increased pressures on the left side of the heart.

By causing an imbalance of the Starling forces acting across the capillaries, increased hydrostatic pressure in the pulmonary circulation favours the development of pulmonary oedema. With cardiogenic pulmonary oedema, capillary permeability is likely to remain unchanged.

Biventricular failure will result as a result of the pressure changes being transmitted to the right side of the circulation. The patient’s systemic vascular resistance is likely to be elevated as well, but it is not the most likely cause of his symptoms. The patient is suffering from cardiogenic shock as a result of biventricular failure. The patient has low cardiac output and is hypotensive. Right ventricular filling pressures are elevated, indicating right ventricular dysfunction.

Giardiasis is known to have a longer incubation time and doesn’t cause bloody diarrhoea.

Cholera usually doesn’t cause bloody diarrhoea.

Generally, most of the E.coli strains do not cause bloody diarrhoea.

Diverticulitis can be a cause of bloody stool but the history here points out to an infectious cause.

Campylobacter infection is the most probable cause as it is characterized by a prodrome, abdominal pain and bloody diarrhoea

The cardiac muscle’s contractile fibres have a much more stable resting potential than its conductive fibres. In the ventricular fibres it is -90mV and in the atrial fibres it is -80mV.

The cardiac action potential has several phases which have different mechanisms of action as seen below:

Phase 0: Rapid depolarisation – caused by a rapid sodium influx.
These channels automatically deactivate after a few ms. (QRS complex)

Phase 1: caused by early repolarisation and an efflux of potassium.

Phase 2: Plateau – caused by a slow influx of calcium.

Phase 3 – Final repolarisation – caused by an efflux of potassium.

Phase 4 – Restoration of ionic concentrations – The resting potential is restored by Na+/K+ATPase.
There is slow entry of Na+into the cell which decreases the potential difference until the threshold potential is reached. This then triggers a new action potential

Of note, cardiac muscle remains contracted 10-15 times longer than skeletal muscle.

Different sites have different conduction velocities:
1. Atrial conduction – Spreads along ordinary atrial myocardial fibres at 1 m/sec

2. AV node conduction – 0.05 m/sec

3. Ventricular conduction – Purkinje fibres are of large diameter and achieve velocities of 2-4 m/sec, the fastest conduction in the heart. This allows a rapid and coordinated contraction of the ventricles

The right coronary artery supplies the right ventricle, the right atrium, the sinoatrial (SA) node and the atrioventricular (AV) node.

The circumflex artery originates from the left coronary artery and is supplied by it.

The most likely diagnosis is a spinal epidural haematoma, a neurological emergency. A full examination must be carried out to determine the nature of the neurological problem before conducting any investigations or imaging.

The effects of spinal anaesthesia should have worn off by this time point, and the severe back pain is a red flag.

The patient will also require an urgent neurological team referral as a spinal epidural haematoma requires immediate evacuation for spinal decompression. Analgesics may be prescribed for pain management.

Heparin would have been fully metabolised and so a reversal is unnecessary.

A spinal epidural haematoma is a pooling of blood in the epidural space, which can cause compression of the spinal cord. Its presenting symptoms are:

Usually begins with severe backpain and percussion tenderness
Cauda equina syndrome
Paralysis of the lower extremities.
If infected, a fever occurs in 66% of cases
Lower limb weakness developing after stopping an epidural infusion or weakness of the lower limbs which does not resolve within four hours of cessation of infusion of epidural local anaesthetic
Meningism.

The ?-2 adrenoceptor has three subtypes (2a, 2b and 2c). The receptors are generally presynaptic, meaning they prevent noradrenaline from being released at nerve endings. Both the central and peripheral nerve systems are affected by the ?-2 agonists. ?-2 agonists cause drowsiness, analgesia, and euphoria centrally in the locus coeruleus (in the brainstem), lower the MAC of volatile anaesthetic drugs, and are used to treat acute withdrawal symptoms in chronic opioid addicts.

The most common impact of ?-2 agonists on heart rate is bradycardia. The adrenoreceptors ?-1 and ?-2 are blocked by phenoxybenzamine.

Clonidine is a selective agonist for the ? -2 receptor, having a 200:1 affinity ratio for the ?-2: ?-1 receptors, respectively.

Tizanidine is similar to clonidine but has a few key variances. It has the same sedative, anxiolytic, and analgesic characteristics as clonidine, although for a shorter period of time and with less effect on heart rate and blood pressure.

Dexmedetomidine, like clonidine, is a highly selective ?-2 adrenoreceptor agonist having a higher affinity for the ?-2 receptor. In the case of ?-2: ?-1 receptors, the affinity ratio is 1620:1. It has a biphasic blood pressure impact and induces a brief rise in blood pressure and reflex bradycardia (activation of ?-2b subtypes of receptors in vascular smooth muscles), followed by a reduction in sympathetic outflow from the brainstem and hypotension/bradycardia.

A prodrug is methyldopa. It blocks the enzyme dopa-decarboxylase, which converts L-dopa to dopamine (a precursor of noradrenaline and adrenaline). It is also converted to alpha-methyl noradrenaline, a centrally active agonist of the ?-2 adrenoreceptor. These two processes contribute to its blood pressure-lowering effect. Without a rise in heart rate, cardiac output is generally maintained. The heart rate of certain patients is slowed.

Phentolamine is a short-acting antagonist of peripheral ?-1 and ?-2 receptors that causes peripheral vascular resistance to reduce and vasodilation to increase. It’s used to treat hypertensive situations that aren’t life threatening (e.g. hypertension from phaeochromocytoma).

A baroreceptor reflex commonly causes reflex tachycardia when systemic vascular resistance drops.

Electromagnetic waves are categorized according to their frequency or equivalently according to their wavelength. Visible light makes up a small part of the full electromagnetic spectrum.

Electromagnetic waves with shorter wavelengths and higher frequencies include ultraviolet light, X-rays, and gamma rays. Electromagnetic waves with longer wavelengths and lower frequencies include infrared light, microwaves, and radio and televisions waves.

Different electromagnetic waves according to their wavelength from shorter to longer are X-rays, ultraviolet radiations, visible light, infrared radiation, radio waves. X-ray among electromagnetic waves has the shortest wavelength and higher frequency with wavelengths ranging from 10*-8 to 10* -12 and corresponding frequencies.

This clinical trial consists over 1000 patients being evaluated for the response to a new treatment against a currently licensed treatment for ulcerative colitis. Therefore, it is comparing its efficacy to an established therapeutic or control in a larger population of volunteers. These are the characteristics of a phase III clinical trial.

Recall bias introduced when participants in a study are systematically more or less likely to recall and relate information on exposure depending on their outcome status.

In procedure bias, the researcher decides assignment of a treatment versus control and assigns particular patients to one group or the other non-randomly. This is unlikely to have occurred in this case, although it is not mentioned specifically.

Self Selection or volunteer bias occur when those subjects are selected to participate in the study who are not the representative of the entire target population. those subjects may be from high socio-economic status and practice those activities or lifestyle that improves their health.

Lead-time bias occurs when a disease is detected by a screening test at an earlier time point rather than it would have been diagnosed by its clinical appearance. In this bias, earlier detection improves the survival time in the intervention group.

Daptomycin alters the curvature of the membrane, which creates holes that leak ions. This causes rapid depolarization, resulting in loss of membrane potential. Thus it interferes with the outer membrane of gram-positive bacteria resulting in cell death.

Even though aprotinin reduces fibrinolysis and therefore bleeding, there is an associated increased risk of death. It was withdrawn in 2007.
Protein C is dependent upon vitamin K and this may paradoxically increase the risk of thrombosis during the early phases of warfarin treatment.

The coagulation cascade include two pathways which lead to fibrin formation:
1. Intrinsic pathway – these components are already present in the blood
Minor role in clotting
Subendothelial damage e.g. collagen
Formation of the primary complex on collagen by high-molecular-weight kininogen (HMWK), prekallikrein, and Factor 12
Prekallikrein is converted to kallikrein and Factor 12 becomes activated
Factor 12 activates Factor 11
Factor 11 activates Factor 9, which with its co-factor Factor 8a form the tenase complex which activates Factor 10

2. Extrinsic pathway – needs tissue factor that is released by damaged tissue)
In tissue damage:
Factor 7 binds to Tissue factor – this complex activates Factor 9
Activated Factor 9 works with Factor 8 to activate Factor 10

3. Common pathway
Activated Factor 10 causes the conversion of prothrombin to thrombin and this hydrolyses fibrinogen peptide bonds to form fibrin. It also activates factor 8 to form links between fibrin molecules.

4. Fibrinolysis
Plasminogen is converted to plasmin to facilitate clot resorption

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 usual method of calculating the dose of a drug to be given to patients of normal weight is to use total body weight (TBW). This is because the lean body weight (LBW) and ideal body weight (IBW) dosing scalars are similar in these patients.

Because the LBW and fat mass do not increase in proportion in patients with morbid obesity, this is not the case. Drugs that are lipid soluble, such as propofol or thiopentone, can cause a relative overdose. Lean body mass is a better scalar in these situations.

Suxamethonium has a small volume of distribution, so the dose is best calculated using the TBW to ensure optimal and deep intubating conditions. The higher dose was justified because these patients’ plasma cholinesterase activity was elevated.

Other scalars include:

The dose of highly lipid soluble drugs like benzodiazepines, thiopentone, and propofol can be calculated using lean body weight (LBW). The formula LBW = IBW + 20% can be used on occasion.

Fentanyl, rocuronium, atracurium, vecuronium, morphine, paracetamol, bupivacaine, and lidocaine are all administered with LBW.

Formulas can be used to calculate the ideal body weight (IBW). There are a number of drawbacks, including the fact that patients of the same height receive the same dose, and the formulae do not account for changes in body composition associated with obesity. Because IBW is typically lower than LBW, administering a drug based on IBW may result in underdosing. The body mass index (BMI) isn’t used to calculate drug dosage directly.

Thermodilution is the most common dilution method used to measure cardiac output (CO) in a hospital setting.

During the procedure, a Swan-Ganz catheter, which is a specialized catheter with a thermistor-tip, is inserted into the pulmonary artery via the peripheral vein. 5-10mL of a cold saline solution with a known temperature and volume is injected into the right atrium via a proximal catheter port. The solution is cooled as it mixes with the blood during its travel to the pulmonary artery. The temperature of the blood is the measured by the catheter and is profiled using a computer.

The computer also uses the profile to measure cardiac output from the right ventricle, over several measurements until an average is selected.

Cardiac output changes at each point of respiration, therefore to get an accurate measurement, the same point during respiration must be used at each procedure, this is usually the end of expiration, that is the end-expiratory pause.

Smoking is a major risk factor associated with perioperative respiratory and cardiovascular complications. Evidence also suggests that cigarette smoking causes imbalance in the prostaglandins and promotes vasoconstriction and excessive platelet aggregation. Two of the constituents of cigarette smoke, nicotine and carbon monoxide, have adverse cardiovascular effects. Carbon monoxide increases the incidence of arrhythmias and has a negative ionotropic effect both in animals and humans.

Smoking causes an increase in carboxyhaemoglobin levels, resulting in a leftward shift in which appears to represent a risk factor for some of these cardiovascular complications.

There are two mechanisms responsible for the leftward shift of oxyhaemoglobin dissociation curve when carbon monoxide is present in the blood. Carbon monoxide has a direct effect on oxyhaemoglobin, causing a leftward shift of the oxygen dissociation curve, and carbon monoxide also reduces the formation of 2,3-DPG by inhibiting glycolysis in the erythrocyte. Nicotine, on the other hand, has a stimulatory effect on the autonomic nervous system. The effects of nicotine on the cardiovascular system last less than 30 min.

Compliance of the respiratory system describes the expandability of the lungs and chest wall. There are two types of compliance: dynamic and static.

Dynamic compliance describes the compliance measured during breathing, which involves a combination of lung compliance and airway resistance. Defined as the change in lung volume per unit change in pressure in the presence of flow.

Static compliance describes pulmonary compliance when there is no airflow, like an inspiratory pause. Defined as the change in lung volume per unit change in pressure in the absence of flow.

For example, if a person was to fill the lung with pressure and then not move it, the pressure would eventually decrease; this is the static compliance measurement. Dynamic compliance is measured by dividing the tidal volume, the average volume of air in one breath cycle, by the difference between the pressure of the lungs at full inspiration and full expiration. Static compliance is always a higher value than dynamic

Static compliance can be computed using the formula:

Cstat = Tidal volume/Plateau pressure – PEEP

Substituting the values given,

Cstat = 800/50-10
Cstat = 20 ml/cmH2O

Funnel plot is essentially a scatterplot of the effect of treatment against a particular measure of study precision. Its primal purpose is to serve as a visual aid and help in detection of bias or systematic heterogenity.

An echocardiogram provides real-time visualisation of cardiac structures. The ejection fraction (EF) is normally measured using this system.

The ejection fraction (EF) can be deduced mathematically if the patient’s end-diastolic volume (EDV), end-systolic volume (ESV) and stroke volume (SV) are known, as:

SV = EDV – ESV, and

EF = SV/EDV x 100

The normal range for EF is >55-70%.

For this patient,

SV= 40 – 30 = 10 mL, therefore

EF = 10/40 x 100 = 25%

The common peroneal (fibular) nerve is a peripheral nerve in the lower limb. It arises of the L4-S2 nerve roots and has sensory and motor innervations:

Sensory: Provides innervation of the lateral leg and foot dorsum.

Motor: Provides innervation of the short head of the biceps femoris, as well as muscles of the anterior and lateral leg compartments.

It is the most commonly damaged nerve in the lower extremity, as it is easily compressed by a plaster cast or injured when the fibula is fractured.

Damage to the common peroneal nerve will result in loss of dorsiflexion at ankle (footdrop, as feet are permanently plantarflexed), with the accompanying high stepping gait.

The saphenous and sural nerve only provide sensory innervation.

The tibial nerve arises from the sciatic nerve (like the common peroneal), but it provides motor innervation to the posterior leg compartments and intrinsic foot muscles. Injury to the tibial nerve will cause loss of plantar flexion, toe flexion and weakened foot inversion.

Extreme hip flexion into the lithotomy or Lloyd-Davies position can result in stretch damage to the neurones (sciatic and obturator nerves) or by applying direct pressure (femoral nerve compression).

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.

Adenosine is the first line for AV nodal re-entry tachycardia. An initial dose of 6 mg is given, and a consequent second dose or third dose of 12 mg is administered if the initial dose fails to terminate the arrhythmia.

Aside from Adenosine, a vagal manoeuvre (e.g. carotid massage) is done to help terminate the supraventricular arrhythmia.

Amiodarone is not a first-line drug for supraventricular tachycardias. Digoxin and Propranolol can be considered if the arrhythmia is of a narrow complex irregular type. Verapamil is an alternative to Adenosine if the latter is contraindicated.

The clinical signs suggest a class II haemorrhage – 15-30% of circulating blood volume has been lost.

Pelvic fractures are associated with significant concealed haemorrhage (>2000 ml) and may require aggressive fluid resuscitation. Other priorities include stabilisation of the fracture(s) and pain relief.

The Advanced Trauma Life Support (ATLS) classification of haemorrhagic shock is as follows:

Class I haemorrhage (blood loss up to 15%):
<750 ml of blood loss
Minimal tachycardia
No changes in blood pressure, RR or pulse pressure
Normally not require fluid replacement as will be restored in 24 hours, but in trauma correct.

Class II haemorrhage (15-30% blood volume loss):
Uncomplicated haemorrhage requiring crystalloid resuscitation
Represents about 750 – 1500 ml of blood loss
Tachycardia, tachypnoea and a decrease in pulse pressure (due to a rise in diastolic component due action of catecholamines)
Minimal systolic pressure changes
Anxiety, fright or hostility
Can usually be stabilised by crystalloid, but may later require a blood transfusion.

Class III haemorrhage (30-40% blood volume loss):
Complicated haemorrhagic state in which at least crystalloid and probably blood replacement are required
Classical signs of inadequate perfusion, marked tachycardia, tachypnoea, significant changes in mental state and measurable fall in systolic pressure
Almost always require blood transfusion, but decision based on patient initial response to fluid resuscitation.

Class IV haemorrhage (> 40% blood volume loss):
Preterminal event patient will die in minutes
Marked tachycardia, significant depression in systolic pressure and very narrow pulse pressure (or unobtainable diastolic pressure)
Mental state is markedly depressed
Skin cold and pale
Need rapid transfusion and immediate surgical intervention.

Loss of >50% results in loss of consciousness, pulse and blood pressure.

The route of choice is an arm vein (cephalic) with one or two large bore cannula. This will enable initial aggressive fluid resuscitation. A central line can be inserted at a later stage if central venous monitoring is deemed necessary. If a suitable peripheral vein cannot be cannulated with a large bore cannula then the internal jugular vein could be accessed rapidly (preferably ultrasound guided).

Intravenous access below the diaphragm in this case is inadvisable when other routes are available.

For establishing a cause effect relationship, following criteria must be met:

1. Coherence & Consistency

2. Temporal Precedence

3. Specificity

As can be seen, sensitivity (The probability of a positive test) is not among these deciding factors..

Chi-square test is used to determine the statistically significant different between categorical variables. It also determines the difference between expected frequencies and the observed frequencies.

Mann Whitney U test is used to determine the statistically significant different between two independent groups.

Wilcoxon’s test is the test of dependency. it determines the statistically significant difference between two dependent groups.

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.

ANOVA (analysis of variance) is similar to student’s t-test.

ANOVA is a statistical method used to determines the statistically significant difference between the mean of more than two group. In this experiment as we are dealing with three different group, ANOVA is most suitable test to determine the difference between each groups.

Phenytoin, Carbamazepine, and Valproate act by inhibiting the sodium channels when these are open. These drugs also prolong the inactivated stage of these channels (Sodium channels are refractory to stimulation till these reach the closed/ resting phase from inactivated phase)

Carbamazepine is the drug of choice for partial seizures and trigeminal neuralgia

It can have neurotoxic side effects. Major neurotoxic effects include dizziness, headache, ataxia, vertigo, and diplopia

After single oral doses of carbamazepine, the absorption is fairly complete and the elimination half-life is about 35 hours (range 18 to 65 hours). During multiple dosing, the half-life is decreased to 10-20 hours, probably due to autoinduction of the oxidative metabolism of the drug.

It is metabolized in liver into active metabolite, carbamazepine-10,11-epoxide.

Soda-lime contains mostly calcium hydroxide (about 94%) and remaining sodium hydroxide.

CO2 + Ca(OH)2 → CaCO3 + H2O + heat
Here in this exothermic reaction, we can see that the production of calcium carbonate does not require heat.

When soda lime is allowed to dry with subsequent use of desflurane, isoflurane, and enflurane, it can lead to the generation of carbon monoxide.

Silica hardens the granules and can thus prevent disintegration.

The size of soda-lime granules is 4-8 mesh because it allows sufficient surface area for chemical reaction to occur without critically increasing the resistance to airflow.

Mivacurium is metabolised primarily by plasma cholinesterase at an In vitro rate of about 70% that of succinylcholine. Mivacurium is contraindicated in patients with genetic and acquired plasma cholinesterase deficiencies.

The clearance of atracurium is by Hoffman degradation and ester hydrolysis in the plasma and is independent of both hepatic and renal function.

Rocuronium is eliminated primarily by the liver after metabolises to a less active metabolite, 17-desacetyl-rocuronium. Its duration of action is not affected much by renal impairment.

Vecuronium undergoes hepatic metabolism into 3-desacetyl-vecuronium which has 50-80% the activity of the parent drug. It undergoes biliary (40%) and renal excretion (30%). The aminoglycoside antibiotics possess additional neuromuscular blocking activity. The potency of gentamicin > streptomycin > amikacin. Calcium can be used to reverse the muscle weakness produced by gentamicin but not neostigmine. When vecuronium and gentamycin are given together the effect on neuromuscular blockade is synergistic.

Significant residual neuromuscular block 2 hours after the administration of these drugs is unlikely In this scenario.

Any recovery from neuromuscular blockade with suxamethonium in a patient with deficiency of plasma cholinesterase demonstrate four twitches on a train of four count.

The process used in the study is Delphi method. This method kicks off with an open ended questionnaire and uses its responses as a survey instrument for the next round in which each of the participants is asked to rate the items that the investigators have summarized on the basis of the data collected in the first round.

Any disagreement is further discussed in phases to come on the basis of information obtained from previous phases.