Propofol infusion syndrome is a rare but extremely dangerous complication of propofol administration

Common organ systems affected by PRIS include the following:
1. cardiovascular
widening of QRS complex, Brugada syndrome-like patterns (particularly type 1), ventricular tachyarrhythmias, cardiogenic shock, and asystole

2. hepatic
Liver enzymes elevation, hepatomegaly, and steatosis

3. skeletal muscular
myopathy and overt rhabdomyolysis

4. renal
Hyperkalaemia, acute kidney injury

5. metabolic
High anion gap metabolic acidosis (due to elevation in lactic acid)

The SI unit of pressure is the pascal (Pa) and it is equal to one newton (N) per square meter (m2) or N/m2.

1 atmosphere (atm) is the equivalent of:

101325 Pa760 mmHg
1.01325 bar
1033.23 cmH2O.
14.69 pounds per square inch (psi)
1013.25 millibar (mbar) or hectopascals (hPa), and

14.69 psi is equal to one atmosphere. The other values are equal to two atmospheres of pressure.

In situations of poisoning or drug overdose with acid dugs like salicylates and barbiturates, forced alkaline diuresis may be used.

With regards to overdose with alkaline drugs, forced acid diuresis is used.

By changing the pH of the urine, the ionised portion of the drug stays in the urine, and this prevents its diffusion back into the blood. Charged molecules do not readily cross biological membranes.

The process involves the infusion of specific fluids at a rate of about 500ml per hour. This requires monitoring of the central venous pressure, urine output, plasma electrolytes, especially potassium, and blood gas analysis.

The fluid regimen recommended is:
500ml of 1.26% sodium bicarbonate (not 200ml of 8.4%)
500ml of 5% dextrose and
500ml of 0.9% sodium chloride.

The external carotid artery has eight important branches:
1. Superior thyroid artery
2. Ascending pharyngeal artery
3. Lingual artery
4. Facial artery
5. Occipital artery
6. Posterior auricular artery
7. Maxillary artery (terminal branch)
8. Superficial temporal artery (terminal branch)

There is no mandibular artery but the first part of the maxillary artery is called the mandibular part as it is posterior to the lateral pterygoid muscle.
The maxillary artery is divided into three portions by its relation to the lateral pterygoid muscle:
first (mandibular) part: posterior to the lateral pterygoid muscle
second (pterygoid or muscular) part: within the lateral pterygoid muscle
third (pterygopalatine) part: anterior to the lateral pterygoid muscle

The extrinsic pathway is considered as the main pathway of coagulation cascade.

Heparin is known to inhibit the activation of coagulation factors 2,9,10, and 11.

The extrinsic and intrinsic pathways meet at the activation of coagulation factor 10.

Fibrinogen is converted into Fibrin in the presence of Thrombin. Plasminogen is converted into plasmin during fibrinolysis to breakdown fibrin clot.

The trochlear nerve (CN IV) is the fourth and smallest cranial nerve. It’s role is to provide somatic motor innervation of the superior oblique muscle which is responsible for oculomotion.

Injury to the trochlear nerve will result in vertical diplopia, which worsens when looking downwards or inwards. This diplopia presents as an upward deviation of the eye with a head tilt away from the site of the lesion.

The abducens nerve (CN VI) provides somatic motor innervation for the lateral rectus muscle which functions to abduct the eye. Injury to this nerve will cause diplopia and an inability to abduct the eye, causing the patient to have to rotate their head to look sideways.

The facial nerve (CN VII) provides sensory, motor and parasympathetic innervations. It’s motor aspect controls the muscles of facial expression. Damage will cause paralysis of facial expression.

The oculomotor nerve (CN III) provides motor and parasympathetic innervations. Its motor component controls most of the other extraocular muscles. Damage to it will result in ptosis, dilatation of the pupil and a down and out eye position.

The ophthalmic division of the trigeminal nerve (CN VI) is responsible for sensory innervation of skin, mucous membranes and sinuses of the upper face and scalp.

Platelets are fragments of megakaryocytes and they are encapsulated by membrane.

They have no nucleus but are metabolically active and are able to express membrane receptors and release stored substances when triggered. adenosine diphosphate and serotonin are 2 of its content.

Because they have no nucleus, they are not able to produce new proteins. This is why aspirin and other drugs affect function for their entire lifespan after exposure. Its lifespan is approximately 9-10 days in normal individuals.

Platelets does NOT PRODUCE prostacyclin but are able to produce nitric oxide, prostaglandins and thromboxane.

The left gastric artery is the smallest branch that originates from the coeliac trunk—the coeliac trunk branches of the abdominal aorta at the vertebral level of T12.

The left gastric artery runs along the superior portion of the lesser curvature of the stomach. A peptic ulcer that is serious enough to erode through the stomach mucosa into a branch of the left gastric artery can cause massive blood loss in the stomach, leading to hematemesis. The patient also takes Naproxen, a non-steroidal anti-inflammatory drug that is a common cause for peptic ulcers in otherwise healthy patients.

The left gastric artery is responsible for 85% of upper GI bleeds. In cases refractory to initial treatment, angiography is sometimes needed to embolise the vessel at its origin and stop bleeding. During an angiogram, the radiologist will enter the aorta via the femoral artery, ascend to the level of the 12th vertebrae and then enter the left gastric artery via the coeliac trunk.

The important landmarks of vessels arising from the abdominal aorta at different levels of vertebrae are:

T12 – Coeliac trunk

L1 – Left renal artery

L2 – Testicular or ovarian arteries

L3 – Inferior mesenteric artery

L4 – Bifurcation of the abdominal aorta

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

A critical factor for survival of acute mesenteric ischemia is early diagnosis and intervention. Angiography uses X-ray and contrast dye to image arteries and identify the severity of ischemia or obstruction.

The celiac axis is the first branch of the abdominal aorta and supplies the entire foregut (mouth to the major duodenal papilla). It arises at the level of vertebra T12. It has three major branches:
1. Left gastric
2. Common hepatic
3. Splenic arteries

There are some important landmarks of vessels at different levels of vertebrae that need to be memorized.

T12 – Coeliac trunk

L1 – Left renal artery

L2 – Testicular or ovarian arteries

L3 – Inferior mesenteric artery

L4 – Bifurcation of the abdominal aorta

Medical gas cylinders are made up of molybdenum steel but not cast iron. They are checked and assessed at a regular interval.

At least one cylinder in each hundred are tested for tensile, pressure, smash, twist and straightening.

Nitrous Oxide cylinders contain a mixture of liquid and vapour at a pressure of approx. 4500 kPa or 45 Bar. Carbon dioxide cylinder contain gas at the pressure of 5000kPa.

The filling ratio is the ratio of mass of liquified gas in the cylinder to the mass of water required to fill the cylinder at the temperature of 15ºC. In the united kingdom, filling ratio of liquid nitrous oxide is 0.75. The cylinders are usually attached to the anaesthetic machine. As nitrous oxide is an N-methyl-d-aspartate receptor antagonist that may reduce the incidence of chronic post-surgical pain.

The metabolism of drugs in the liver occurs in 3 phases

Phase I: This involves functionalization reactions, which are of 3 types, namely hydrolysis, oxidation and reduction reactions catalysed by the cytochrome P450 (CYP) enzymes.

Phase II: This involves conjugation or acetylation reactions. The goal is to create water soluble metabolites that can be excreted from the body.

The liver is the second largest organ. It’s smallest functional unit is the acinus which is divided into 3 zones:

Zone I (periportal): This zone receives the largest amount of oxygen supply as it is the closest to the blood vessels. It is the site of plasma protein synthesis.

Zone II (mediolobular): This is located between the portal triad and central vein.

Zone III (centrilobular): This is closest to the central vein and receives the least amount of oxygen supply.

Kupffer cells are specialized macrophages found in the periportal zone of the liver, and function to remove foreign particles and breakdown red blood cells via phagocytosis.

Ito cells are fat-storing liver cells found in the space of Disse. Their function is to take-uo, store and secrete retinoids, as well as manufacture and release proteins that make up the extracellular matrix.

Pulmonary vascular resistance (PVR) refers to the resistance to blood flow to the left atrium from the pulmonary artery.
It is derived mathematically by:

PVR = MPAP – PCWP
CO
where,
MPAP: Mean pulmonary artery pressure
PCWP: Pulmonary capillary occlusion pressure
CO: Cardiac output

For this patient:
PVR = 10 – 5 = 1mmHg
5

Remember, multiply by correction factor 80 to change units:

PVR = 1mmHg x 80 = 80 dynes·s·cm-5

Normal values range between 20-130 dynes·s·cm-5

The important landmarks of vessels arising from the abdominal aorta at different levels of vertebrae are:

T12 – Coeliac trunk

L1 – Left renal artery

L2 – Testicular or ovarian arteries

L3 – Inferior mesenteric artery

L4 – Bifurcation of the abdominal aorta

In the neonatal stage, the tongue is usually large and comes to the normal size at the age of 1 year. The vocal cords lie inverse C4 and as it reaches the grown-up position inverse C5/6 by the age of 4 (not 1 year).

Due to the immature cricoid cartilage, the larynx lies more anterior in newborn children. That’s why the cricoid ring is the narrowest part of the paediatric respiratory tract, while in the adults the tightest portion of the respiratory route is vocal cords. The epiglottis is generally expansive and slants at a point of 45 degrees to the laryngeal opening.

The carina is the ridge of the cartilage in the trachea at the level of T2 in newborn (T4 in adults), that separates the openings of right and left main bronchi.

Neonates have a comparatively low number of alveoli and then this number gradually increases to a most extreme by the age of 8 (not 3 years).

Neonates are obligatory nose breathers and any hindrance can cause respiratory issues (e.g., choanal atresia).

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

So,

ARR= (24/120)-(60/240)

ARR= 0.2-0.25

ARR= 0.05 (Numerical Value)

ARR= 5%

Impaired ventricular relaxation reduces diastolic filling and therefore preload.

Decreased blood volume decreases preload due to reduced venous return.

Heart failure is characterized by reduced ejection fraction and therefore stroke volume.

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 (is increased by stroke volume) = 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
Aortic stenosis would decrease stroke volume as end systolic volume would increase.
This is because of an increase in afterload, an increase in resistance that the heart must pump against due to a hard stenotic valve.

Dabigatran template is a prodrug and its active metabolite is a direct thrombin inhibitor. It is a synthetic, reversible, non-peptide thrombin inhibitor. This inhibition of thrombin results in a decrease of fibrin and reduces platelet aggregation.

Drugs like warfarin act by inhibiting the activation of vitamin K-dependent clotting factors. These factors are synthesized by the liver and activated by gamma-carboxylation of glutamate residues with the help of vitamin K. Hydroquinone form of vitamin K is converted to epoxide form in this reaction and regeneration of hydroquinone form by enzyme vitamin K epoxide reductase (VKOR) is required for this activity. Oral anticoagulants prevent this regeneration by inhibiting VKOR, thus vitamin K-dependent factors are not activated. These factors include clotting factors II, VII, IX, and X as well as anti-clotting proteins, protein C and protein S.

A peripherally inserted central catheter (PICC) line is a long, thin tube inserted into the vein of a patient’s arm to gain access to the large central veins near the heart. PICC line is indicated for parenteral nutrition or to deliver medications. They can be used for medium-term venous access, defined as anywhere between several weeks to 6 months.

The veins of choice for PICC are:
1. Basilic
2. Brachial
3. Cephalic
4. Medial cubital vein

The vein of choice is the right basilic vein as it has a large circumference and is located superficially. It has the most straight route to the final destination of PICC (SVC or Right atrium). It courses through the axillary vein, then the subclavian, and finally settles into the SVC. It also has the least number of valves and a shallow angle of insertion when compared to the other veins.

The basilic vein drains the medial end of the dorsal arch of the upper limb, passes along the medial aspect of the forearm, and pierces the deep fascia at the elbow. The basilic vein joins the venae comitantes of the brachial artery to form the axillary vein at the elbow.
The posterior circumflex humeral vein is encountered before the axillary vein. However, a PICC line is unlikely to enter this structure because of its entry angle into the basilic vein.

Both incidence and prevalence are indicators of the disease frequency. While incidence tells us about the number of cases reported per population in a provided time period, prevalence is the factor you should be vigilant about as it tells us about the total number of cases that have been reported in a population at a particular point of time.

In first order kinetics the rate of elimination is proportional to plasma concentration.

Rate of elimination is described by the following equation:

C = C0. e^-kt

Where:
C=drug concentration,
C0= drug concentration at time zero (extrapolated),
k = rate constant and
t = time.

The initial concentration of this drug is 12 mcg/ml therefore:

The plasma concentration will have halved to 6 mcg/ml at 2 hours.
The plasma concentration will have halved to 3 mcg/ml at 4 hours and
The plasma concentration will have halved to 1.5 mcg/ml t 6 hours.

Attributable proportion is the proportion of disease that is caused due to exposure. It refers to the proportion of disease that would be eradicated from a particular population if the disease rate was diminished to match that of the unexposed group.

Risk ratio (relative risk) compares the probability of an event in an exposed (experimental) group to that of an event in the unexposed (control) group. Thus two are not the same.

The attributable risk is the rate of a disease in an exposed group to that of a group that has not been exposed to it i.e. how many deaths did the exposure cause.

The clinical potency of the anaesthetic agent is measured using minimal alveolar concentration(MAC).

MAC and oil: gas partition coefficient is inversely related. Anaesthetic agent Oil/gas partition coefficient and Minimal alveolar concentration (MAC) is given respectively as

Desflurane 18 6
Isoflurane 90 1.2
Nitrous oxide 1.4 104
Sevoflurane 53.4 2
Xenon 1.9 71

With these data, we can conclude Isoflurane is the most potent with the highest oil/gas partition coefficient of 90 and the lowest MAC of 1.2

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.

Flowmeters measure the rate at which a specific gas, that the flowmeter has been calibrated for, passes through. This calibration is done at room temperature and standard atmospheric pressure with an accuracy of +/- 2%.

Reading the flowmeter is done from the top of a bobbin (the midpoint of a ball). Oxygen is the last gas to be added downstream to the mixture delivered to the back bar as a safety feature. This prevents delivery of a hypoxic mixture.

Inaccurate flow measurements occur when the bobbin sticks to the inside wall of the flowmeter. Stannic oxide has been used as a successful antistatic substance thus, reducing the aforementioned risk.

Carbon dioxide being easily delivered is found on some older machines, but those attached flowmeters are limited by a maximum flow of 500 ml /min. Thus avoiding the delivery of a hypercarbic mixture.

The basilar artery is a large vessel that is formed by the union of the vertebral arteries at the junction of the medulla and pons. It lies in the pontine cistern and follows a shallow groove on the ventral pontine surface, extending to the upper border of the pons.

The basilar artery then bifurcates into the two posterior cerebral arteries that form part of the Circle of Willis.

Her symptoms are suggestive of trigeminal neuralgia which is a short, sudden, severe sharp unilateral pain in the facial region. The pain often follows the sensory distribution of the trigeminal nerve (CN V).

The trigeminal nerve gives rise to 3 sensory and 1 motor nuclei. Neuralgia can arise from any of the 3 sensory divisions.

The ophthalmic division gives rise to 3 further sensory branches, which are the frontal, lacrimal and nasociliary.

The frontal branch of the ophthalmic division of the trigeminal nerve is responsible for the innervation of the area in question.

The superior alveolar dental, zygomatic and sphenopalatine nerves are all branches arising from the maxillary division of the trigeminal nerve.

The mandibular division of the trigeminal nerve provides sensory and motor innervation. The sensory innervation is carried out by the auriculotemporal nerve which supplies the lower third of the face, while the motor fibres are responsible for controlling the muscles of mastication.

The somatic sensory branches of the vagus nerve are responsible for sensory innervation of the external acoustic meatus and tympanic membrane.

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

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

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

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

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

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

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

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

The attributable risk is the rate of a disease in an exposed group to that of a group that has not been exposed to it. It involves the measure of association that is pertinent to making decisions for the individuals.

After the carotid body, the thyroid gland is the second most richly vascular organ in the body.

The global blood flow to the thyroid gland can be measured using:
1. Colour ultrasound sonography
2. Quantitative perfusion maps using MRI of the thyroid gland using an arterial spin labelling (ASL) method.

This table shows the blood flow to various organs of the body at rest:
Organ Blood Flow(ml/minute/100g)
Hepatoportal 58
Kidney 420
Brain 54
Skin 13
Skeletal muscle 2.7
Heart 87
Carotid body 2000
Thyroid gland 560

Crystalloids recommended for fluid resuscitation include 0.9% N saline and Hartmann’s solution(a physiological solution). 0.9% N. saline is not a physiological solution for the following reasons:

Compared with the normal range of 98-102 mmol/L, its chloride concentration is high (154 mmol/L)
It lacks calcium, magnesium, glucose and potassium
It does not have bicarbonate or bicarbonate precursor buffer necessary to maintain plasma pH within normal limits

There is a difference in the activity (concentration) of strong ions at a physiological pH. This imbalance can explain abnormalities of acid base balance. A normal strong ion difference (SID) is in the order of 40.

SID = ([Na+] + [K+] + [Ca2+] + [Mg2+]) – ([Cl-] + [lactate] + [SO42-])

This imbalance is made up with the weaker anions to maintain electrical neutrality.
Administration of a large volume of 0.9% normal saline during resuscitation results in excessive chloride administration and this impairs renal bicarbonate reabsorption. The SID of 0.9% normal saline is 0 (Na+ = 154mmol/L and Cl- = 154mmol/L = 154 – 154 = 0). A large volume of NS will decrease the plasma SID causing an acidosis.

Other causes of a hyperchloremic acidosis are:

Diabetic ketoacidosis
Total Parenteral Nutrition
Overdose of ammonium chloride and hydrochloric acid
Gastrointestinal losses of bicarbonate like in diarrhoea and pancreatic fistula
Proximal renal tubular acidosis with failure of bicarbonate reabsorption