Hypoxic Pulmonary vasoconstriction (HPV) reflects the constriction of small pulmonary arteries in response to hypoxic alveoli (.i.e.; PO2 below 80-100mmHg or 11-13kPa).

These blood vessels become independent of the nerve stimulus, when blood with a high PO2 flows through the lung which contains a low alveolar PO2.

Thus a low PO2 within the alveoli has been shown to impact on hypoxic pulmonary vasoconstriction (HPV) more than a low PO2 within the blood.

HPV results in the blood flow being directed away from poorly ventilated areas of the lung and helps to reduce the ventilation/perfusion mismatch (not increase).

In animals, volatile anaesthetic agents can diminish HPV, while in adults, the evidence proves less persuading, in spite of the fact that it certainly doesn’t strengthen the effects.

HPV response will be suppressed by 20 parts per million (ppm) of nitric oxide.

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.

Standard error can be calculated by the following formula:

Standard Error= (Standard Deviation)/ˆš(Sample Size)
= (12) / ˆš(64)
= 12 / 8
= 1.5

The international system of units, or system international d’unites (SI) is a collection of measurements derived from expanding the metric system.

There are seven base units, which are:

Metre (m): a unit of length
Second (s): a unit of time
Kilogram (kg): a unit of mass
Ampere (A): a unit of electrical current
Kelvin (K): a unit of thermodynamic temperature
Candela (cd): a unit of luminous intensity
Mole (mol): a unit of substance.

When the convulsion lasts for five or more than five minutes, or if there are recurrent episodes of convulsions in a 5 minute period without returning to the baseline, it is termed as Status Epilepticus.
The first priority in the patient with seizures is maintaining the airway, breathing, and circulation.

Guideline for the management of Status Epilepticus in children by Advanced Life Support Group is as follow:

Step 1 (Five minutes after the start of seizures):

If intravascular access is available start treatment with lorazepam 0.1 mg/kg IV
If no intravascular access then give buccal midazolam 0.5 mg/kg or rectal diazepam 0.5 mg/kg.

Step 2 (Ten minutes after the start of seizure):

If the convulsions continue then a second dose of benzodiazepine should be given. Senior should be called on-site and phenytoin should be prepared.
No more than two doses or benzodiazepines should be given (including any doses given before arrival at the hospital)
If still no IV access then obtain intraosseous access (IO).

Step 3 (Ten minutes after step 2)

Senior help along with anaesthetic/ICU help should be sought
Phenytoin 20 mg/kg IV over 20 minutes
If the seizure stops before the full dose of phenytoin is given then the infusion should be completed as this provides up to 24 hours of anticonvulsant effect
In children already receiving phenytoin as treatment for epilepsy then an alternative is phenobarbitone 20 mg/kg IV over five minutes
Once the phenytoin is started, senior staff may wish to give rectal paraldehyde 0.4 mg/kg although this is no longer included in the routine algorithm recommended by APLS.

Step 4 (20 minutes after step 3)

If 20 minutes after starting phenytoin the child remains in status epilepticus then rapid sequence induction of anaesthesia with thiopentone and a short acting paralysing agent is needed and the child transferred to paediatric intensive care.

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.

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 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).

Elimination of phenytoin from the body follows first-order kinetics. This means that the rate of elimination is proportional to plasma concentration.

The rate of elimination can be described by the equation:

C = C0·e-kt

Where:

C = drug concentration
C0 = drug concentration at time zero (extrapolated)
k = Rate constant
t = Time

Enzyme systems become saturated when phenytoin concentrations exceed the normal range and elimination of the drug becomes zero-order. At this point, the drug is metabolised at a fixed rate and metabolism is independent of plasma concentration.

Aspirin and ethyl alcohol are other drugs that behave this way.

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.

Decreased stroke volume causes decreased ejection fraction which results in diastolic dysfunction.
Ejection fraction is not a useful measure in someone with diastolic dysfunction because stroke volume may be reduced whilst end-diastolic volume may be reduced.
Diastolic dysfunction may arise with reduced heart compliance.

Ejection fraction measures of the proportion of blood leaving the ventricles with each beat and is calculated as follows:
Stroke volume / end-diastolic volume.

A healthy ejection fraction is usually taken as 60% (based on a stroke volume of 70ml and end-diastolic volume of 120ml).

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.

The left subclavian artery originates from the aortic arch, while the right subclavian artery originates from the brachiocephalic artery.

The subclavian artery gives off branches on both sides of the body:
1. Vertebral artery
2. Internal thoracic artery
3. Thyrocervical trunk
4. Costocervical trunk
5. Dorsal scapular artery

The superior thyroid artery is the first branch of the external carotid artery. The other branches of the external carotid artery are:
1. Superior thyroid artery
2. Ascending pharyngeal artery
3. Lingual artery
4. Facial artery
5. Occipital artery
6. Posterior auricular artery
7. Maxillary artery
8. Superficial temporal artery.

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.

Approximately 70% of the heart’s ATP requirement is met by cardiac mitochondria through beta-oxidation of fatty acids at rest. The remaining 30% is supplied by glucose.

Amino acids and ketones, in the presence of ketoacidosis, may supply at most 10% of the ATP requirement. And, when in high levels, lactate may also contribute to the ATP requirement of the heart, particularly during moments of high muscular activity.

Once the decision to deliver a baby by caesarean section has been made, it should be carried out with a level of urgency commensurate with the baby’s risk and the mother’s safety.

There are four types of caesarean section urgency:

Category 1: A threat to the life of the mother or the foetus. 30 minutes to make a delivery decision
Category 2 : Maternal or foetal compromise that is not immediately life threatening. In most cases, the decision to deliver is made within 75 minutes.
Category 3 – Early delivery is required, but there is no risk to the mother or the foetus.
Category 4: Elective delivery at a time that is convenient for both the mother and the maternity staff.

There may be evidence of foetal compromise in the example above (late foetal pulse decelerations and a borderline pH).

Blood samples from the foetus:
normal: 7.25 or above
borderline: 7.21 to 7.24
abnormal: 7.20 or below

When a foetal deceleration occurs, the mother should be given oxygen, kept in a left lateral position, and given a tocolytic if the foetal deceleration is hyper stimulating. Maintaining adequate hydration will reduce the likelihood of a caesarean section.

Opioid should be avoided in the caesarean section as it crosses the placental membrane and causes respiratory depression.

Even though inhalational and intravenous anaesthetic agents readily cross the placenta, they do not have significant effects on APGAR score when used in clinical doses.

Vecuronium and suxamethonium are highly polar molecules and thus do not cross the placenta in significant amounts.

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

It can be found as:

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

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

So,

ARR= (43.9-37.3)

ARR= 6.6

NNT= 1000/6.6

NNT=151.5

The clinical picture best describes a probable drug interaction with pethidine.

Phenelzine, a monoamine oxidase (MAO) inhibitor, when given with pethidine, an opioid analgesic, may lead to episodes of hypertension, rigidity, excitation, hyperpyrexia, seizures, coma and death. Studies have shown that pethidine reacts more significantly with MAO inhibitors than morphine.

When pethidine is metabolised to normeperidine, it acts as a serotonin reuptake inhibitor and cause an increase in serotonin levels in the brain. MAO inhibitors can also lead to elevated levels of serotonin because of its mechanism of action by inhibiting the enzyme monoamine oxidase that degrades serotonin.

The excess serotonin levels may lead to serotonin syndrome, of which some of the common precipitating drugs are selective serotonin reuptake inhibitors, MAO inhibitors, tricyclic antidepressants, meperidine, and St. John’s Wort. Onset of symptoms is within hours, which includes fever, agitation, tremor, clonus, hyperreflexia and diaphoresis.

Drug interaction between phenelzine and paracetamol do not commonly precipitate serotonin syndrome.

Neuroleptic malignant syndrome is due to dopamine antagonism, precipitated commonly by antipsychotics. Its onset of symptoms occur in 1 to 3 days, and is characterized by fever, encephalopathy, unstable vitals signs, elevated CPK, and rigidity.

Altered mental status is the most common manifestation of sepsis-associated encephalopathy. Patient also exhibit confusional states and inappropriate behaviour. In some cases, this may lead to coma and death.

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.

The external urethral sphincter functions to provide voluntary control of urine flow from the bladder to the urethra.

It receives its innervation from the branches of the pudendal nerve which originate from S2, S3 and S4.

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= (0.04-0.03)

ARR= 0.01

NNT= 1/0.01

NNT=100

The Delphi technique was developed in the 1950s and is a widely used and accepted method for achieving convergence of opinion concerning real-world knowledge solicited from experts within certain topic areas. Choosing the appropriate subjects is the most important step in the entire process because it directly relates to the quality of the results generated, despite this, there is no exact criterion currently listed in the literature concerning the selection of Delphi participants.

Therefore, due to the potential scarcity of qualified participants and the relatively small number of subjects used in a Delphi study, the ability to achieve and maintain an ideal response rate can either ensure or jeopardize the validity of a Delphi study.

The derived SI unit of force is Newton.
F = m·a (where a is acceleration)
F = 1 kg·m/s2

The joule (J) is a converted unit of energy, work, or heat. When a force of one newton (N) is applied over a distance of one metre (Nm), the following amount of energy is expended:

J = 1 kg·m/s2·m =
J = 1 kg·m2/s2 or 1 kg·m2·s-2

The unit of velocity is metres per second (m/s or ms-1).

The watt (W), or number of joules expended per second, is the SI unit of power:

J/s = kg·m2·s-2/s
J/s = kg·m2·s-3

Pressure is measured in pascal (Pa) and is defined as force (N) per unit area (m2):
Pa = kg·m·s-2/m2
Pa = kg·m-1·s-2

Firstly, always call for an early help. This understanding is at hazard of gastro-oesophageal reflux, the reason a fast arrangement acceptance has been picked for within the first place. The patient isn’t pregnant and the critical surgery isn’t immediate.

The scheme A is to perform a fast arrangement acceptance under ideal conditions and effectively secure the respiratory tract with a tracheal tube.

Whilst no more than three attempts with coordinate laryngoscope (+ 1 endeavour with video laryngoscope) ought to be made to intubate the trachea, the reality is that the suxamethonium is wearing off ought to be borne in mind. One step is to make certain satisfactory neuromuscular blockade at this level, if oxygenation can be kept up by bag-mask ventilation, this might involve the administration of a non-depolarising relaxant. As the surgery isn’t prompt there should be a baseline to stop scheme A at intubation and resort to scheme B.

An elective procedure can be planned at that time.

The first most vital step is to report a failed intubation as this will halt you from continuing to intubate and notify your collaborator that scheme A has failed. Keeping up oxygenation and anaesthesia is additionally critical earlier to the initiation of scheme B.

Do not administer another dose of suxamethonium. If there’s collapse of oxygenation and failure to preserve satisfactory ventilation, then insert a supraglottic airway. Plan D takes after the affirmation of a CICO.

The sacral hiatus is shaped by incomplete midline fusion of the posterior elements of the distal portion of S4 and S5. This inverted U shaped space is covered by the posterior aspect of the sacrococcygeal membrane and is an important landmark in caudal anaesthetic block. Distal most portion of the dural sac and the sacral hiatus usually terminate between levels S1 and S3. The dural sac ends at the level of S2 in adults and S3 in children.

An equilateral triangle is formed between the apex of the sacral hiatus and the posterior superior iliac spines. This triangle is used to determine the location of the sacral hiatus during caudal anaesthetic block.

Selective α1 -Blockers like prazosin, terazosin, doxazosin, and alfuzosin cause a decrease in blood pressure with lesser tachycardia than nonselective blockers (due to lack of α2 blocking action.

The major adverse effect of these drugs is postural hypotension. It is seen with the first few doses or on-dose escalation (First dose effect).

Its half-life is approximately three hours.

It is excreted primarily through bile and faeces (not through kidneys)

The bispectral index (BIS) is one of several systems used in anaesthesiology as of 2003 to measure the effects of specific anaesthetic drugs on the brain and to track changes in the patient’s level of sedation or hypnosis. It is a complex mathematical algorithm that allows a computer inside an anaesthesia monitor to analyse data from a patient’s electroencephalogram (EEG) during surgery. It is a dimensionless number (0-100) that is a summative measurement of time domain, frequency domain and high order spectral parameters derived from electroencephalogram (EEG) signals.

Sleep and anaesthesia have similar behavioural characteristics but are physiologically different but BIS monitors can be used to measure sleep depth. With increasing sleep depth during slow-wave sleep, BIS levels decrease. This correlates with changes in regional cerebral blood flow when measured using positron emission tomography (PET).

BIS shows a dose-response relationship with the intravenous and volatile anaesthetic agents. Opioids produce a clinical change in the depth of sedation or analgesia but fail to produce significant changes in the BIS. Ketamine increases CMRO2 and EEG activity.

BIS is unable to predict movement in response to a surgical stimulus. Some of these are spinal reflexes and not perceived by the cerebral cortex.

BIS is used during cardiopulmonary bypass to measure depth of anaesthesia and an index of cerebral perfusion. However, it cannot predict subtle or significant cerebral damage.

Warfarin prevents reductive metabolism of the inactive vitamin K epoxide back to its active hydroquinone form. Thus, warfarin inhibits the synthesis of vitamin K dependent clotting factors: X, IX, VII, II (prothrombin), and of the anticoagulants protein C and protein S. The therapeutic range for oral anticoagulant therapy is defined in terms of an international normalized ratio (INR). The INR is the prothrombin time ratio (patient prothrombin time/mean of normal prothrombin time for lab)ISI, where the ISI exponent refers to the International Sensitivity Index and is dependent on the specific reagents and instruments used for the determination. A prolonged INR is widely used as an indication of integrity of the coagulation system in liver disease and other disorders, it has been validated only in patients in steady state on chronic warfarin therapy.

Prothrombin complex concentrate (PCC) is used to replace congenital or acquired vitamin-K deficiency warfarin-induced anticoagulant effect, particularly in the emergent setting.

Intravenous vitamin K has a slower onset of action compared to PCC, but is useful for long term therapy.

Fresh frozen plasma (FFP) prepared from freshly donated blood is the usual source of the vitamin K-dependent factors and is the only source of factor V. The factors needed, however, are found in small quantities compared to PCC.

Cryoprecipitate is indicated for hypofibrinogenemia/dysfibrinogenemia, von Willebrand disease, haemophilia A, factor XIII deficiency, and management of bleeding related to thrombolytic therapy.

The GABAA-BZD (Gamma Aminobutyric acid- Benzodiazepine) receptor-Cl (chloride)€“ channel complex is composed
of five α, β, γ, and in some cases δ, ε, θ or π subunits as well.
Based on studies conducted in genetically mutated mice, it has been suggested that BZD receptor isoforms containing the α1
Subunits are involved in mediating sedative, hypnotic, and amnesic actions of BZDs, while those containing α2 subunits mediate anxiolytic and muscle relaxant actions. Diazepam has a similar affinity for BZD receptor containing different (α1 or α2, or α3 or α5 ) subunits, and has broad-spectrum action.

Ketamine, a phencyclidine derivative, is an antagonist at the NMDA receptor. It causes depression of the CNS that is dose dependent and induces a dissociative anaesthetic state with profound analgesia and amnesia.

Ketamine has a chiral centre usually presented as a racemic mixture with two optical isomers, S (+) and R (-) forms. These isomers are in equal proportions. The S (+) isomer is about three times more potent than the R (-) form. The S (+) form is less likely to cause emergence delirium and hallucinations.

Ketamine is extensively metabolised by hepatic microsomal cytochrome P450 enzymes producing norketamine as its main metabolite. Norketamine has a one third to one fifth as potency as its parent compound.
It increases the CMRO2, cerebral blood flow and potentially increase intracranial pressure.