The blood brain barrier (BBB) consists of the ultrafiltration barrier in the choroid plexus and the barrier around cerebral capillaries. The barrier is made by endothelial cells which line the interior of all blood vessels. In the capillaries that form the blood–brain barrier, endothelial cells are wedged extremely close to each other, forming so-called tight junctions.

Outside of the BBB lies the hypothalamus, third and fourth ventricles and the chemoreceptor trigger zone (CTZ).

Water, oxygen and carbon dioxide cross the BBB freely but glucose is controlled. The ability of chemicals to cross the barrier is proportional to their lipid solubility, not their water solubility. It’s ability to cross is inversely proportional to their molecular size and charge.

In neonates, the BBB is less effective than in adults. This is why there is increased passage of opioids and bile salts (kernicterus) into the neonatal brain.

In meningitis, the effectiveness and permeability of the BBB is affected, and as a result, this effect helps the passage of antibiotics which would otherwise not normally be able to cross.

The posterior pituitary is made up mostly of neural tissue. It is responsible for the storage and release of 2 hormones:
– antidiuretic hormone (ADH)
– oxytocin.

These two hormones are synthesised in the supraoptic and paraventricular nuclei of the hypothalamus.

Using a lean body weight metric encompasses a more scientific approach to weight-based dosing. Lean body weight reflects the weight of all ‘non-fat’ body components, including muscle and vascular organs such as the liver and kidneys. As lean body weight contributes to approximately 99% of a drug’s clearance, it is useful for guiding dosing in obesity.

This metric has undergone a number of transformations. The most commonly cited formula derived by Cheymol is not optimal for dosing across body compositions and can even produce a negative result. A new formula has been developed that appears stable across different body sizes, in particular the obese to morbidly obese.

A practical downfall of the calculation of lean body weight (and other body size descriptors) is the numerical complexity, which may not be palatable to a busy clinician. Often limited time is available for prescribing and an immediate calculation is required. Lean body weight calculators are available online, for example in the Therapeutic Guidelines.

Using total body weight assumes that the pharmacokinetics of the drug are linearly scalable from normal-weight patients to those who are obese. This is inaccurate. For example, we cannot assume that a 150 kg patient eliminates a drug twice as fast as a 75 kg patient and therefore double the dose. Clinicians are alert to toxicities with higher doses, for example nephro- and neurotoxicity with some antibiotics and chemotherapeutics, and bleeding with anticoagulants. Arbitrary dose reductions or ‘caps’ are used to avoid these toxicities, but if too low can result in sub-therapeutic exposure and treatment failure.

Body surface area is traditionally used to dose chemotherapeutics. It is a function of weight and height and has been shown to correlate with cardiac output, blood volume and renal function. However, it is controversial in patients at extremes of size because it does not account for varying body compositions. As a consequence, some older drugs such as cyclophosphamide, paclitaxel and doxorubicin were ‘capped’ (commonly at 2 m^2) potentially resulting in sub-therapeutic treatment. Recent guidelines suggest that unless there is a justifiable reason to reduce the dose (e.g. renal disease), total body weight should be used in the calculation of body surface area, until further research is done. Little research into dosing based on body surface area has been conducted for other medicines.

Ideal body weight was developed for insurance purposes not for drug dosing. It is a function of height and gender only and, like body surface area, does not take into account body composition. Using ideal body weight, all patients of the same height and sex would receive the same dose, which is inadequate and generally results in under-dosing. For example a male who has a total body weight of 150 kg and a height of 170 cm will have the same ideal body weight as a male who is 80 kg and 170 cm tall. Both could potentially receive a mg/kg dose based on 65 kg (ideal body weight).

Staphylococcus aureus infection is the most likely cause.

Surgical site infections (SSI) occur when there is a breach in tissue surfaces and allow normal commensals and other pathogens to initiate infection. They are a major cause of morbidity and mortality.

SSI comprise up to 20% of healthcare associated infections and approximately 5% of patients undergoing surgery will develop an SSI as a result.
The organisms are usually derived from the patient’s own body.

Measures that may increase the risk of SSI include:
-Shaving the wound using a single use electrical razor with a disposable head
-Using a non iodine impregnated surgical drape if one is needed
-Tissue hypoxia
-Delayed prophylactic antibiotics administration in tourniquet surgery, patients with a prosthesis or valve, in clean-contaminated surgery of in contaminated surgery.

Measures that may decrease the risk of SSI include:
1. Intraoperatively
– Prepare the skin with alcoholic chlorhexidine (Lowest incidence of SSI)
-Cover surgical site with dressing

In contrast to previous individual RCT’s, a recent meta analysis has confirmed that administration of supplementary oxygen does not reduce the risk of wound infection and wound edge protectors do not appear to confer benefit.

2. Post operatively
Tissue viability advice for management of surgical wounds healing by secondary intention

Use of diathermy for skin incisions
In the NICE guidelines the use of diathermy for skin incisions is not advocated. Several randomised controlled trials have been undertaken and demonstrated no increase in risk of SSI when diathermy is used.

Oxygen is formed by a molecule of oxygen and two molecules of hydrogen with a molecular formula of H2O

The critical temperature is defined as a temperature above which the substance cannot be liquefied, no matter how much pressure is applied.
Water has a critical temperature of -118.6oC. So, it cannot be liquified at room temperature.

Medical oxygen cylinder is stored in a cylinder with a white shoulder and black body. Meanwhile, medial air is stored in cylinders with a white and black shoulder and a French grey body.

The partial pressure of air at a high altitude is less but the relative concentration remains constant.

The question mentions a quantitative, ratio scale data set. The use of mean would be ideal under normal circumstances, however, in this situation median is preferred as it is less sensitive to the skewness of data. The median is usually preferred to other measures of central tendency when your data set is skewed (i.e., forms a skewed distribution)

Thiopental has the longest elimination half-life of 6-15 hours.

Elimination half-life of other drugs are given as:
– Propofol: 5-12 h
– Methohexitone: 3-5 h
– Ketamine: 2 h
– Etomidate: 1-4 h

The incidence of vertebral canal haematoma following neuraxial blockade was reported (third National Audit Project (NAP3)) as 0.85 per 100 000 (95% CI 0-1.8 per 100 000). The incidence following neuraxial blockade in coagulopathic patients is likely to be higher hence coagulopathy remains a relative contraindication for conducting a spinal or epidural. When indicate, risk and benefits are weighed, and it is only performed by experienced personnel in this case.

Acceptable time to perform a block after the last dose of rivaroxaban in a patient with a creatinine clearance of greater than 30mL/minute is 18 hours.

Acceptable time to perform a block after the last dose of subcutaneous LMWH as prophylaxis is 12 hours.

Acceptable time to perform a block after the last dose of subcutaneous UFH as prophylaxis is 4 hours.

Acceptable time to perform a block after the last dose of thrombolytic therapy (streptokinase or alteplase) is 10 days.

Clopidogrel should be stopped 7 days prior to surgery, particularly if a central neuraxial procedure is considered.

Osmolarity refers to the osmotic pressure generated by the dissolved solute molecules in 1 L of solvent. Measurements of osmolarity are temperature dependent because the volume of the solvent varies with temperature. The higher the osmolarity of a solution, the more it attracts water from an opposite compartment.

Osmolarity can be computed using the following formulas:

Osmolarity = Concentration x number of dissociable particles; OR
Plasma osmolarity (Posm) = 2([Na+]) + (glucose in mmol/L) + (BUN in mmol/L)

Posm = 2 (144) + 3.5 + 9.5 = 301 mOsm/L

Suppose there is electrical neutrality, the formula will double the cation activity to account for the anions.

Plasma osmolarity (Posm) = 2([Na+] + [K+]) + (glucose in mmol/L) + (BUN in mmol/L)

Posm = 2 (144 + 6) + 3.5 + 9.5 = 313 mOsm/L

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.

A relative risk of 1 suggests that there is no discernible difference in the outcome whether or not it has been exposed.

A relative risk of less than 1 indicates that probability of occurrence of an event is less if there is exposure.

A relative risk of greater than 1 highlights that an event is most likely to occur if it was provided exposure. Since you believe that exposure (the new drug) would have side effects, the value should be greater than 1.