Table of Contents

In brief, old age affects drug absorption, distribution and elimination in a manner which can be suimmarised by the term "worse". Rarely is anything pharmacologically better in the elderly. They are reluctant to absorb drugs enterally, they are sluggish metabolisers, they more susceptible to side effects and their renal clearance is usually delayed, increasing the half life of most drugs. To say nothing of the tendency of physicians to challenge these physiologically fragile individuals with polypharmacy cocktails. 

One cannot increase in body mass to three or four times the expected norm and still expect to have a normal response to drugs. The pharmacokinetic and pharmacodynamic changes associated with obesity are often surprisingly in the direction of increased function, for instance increased gastric emptying rate, increased hepatic clearance, increased GFR and renal clearance, and increased soluble enzyme activity. A large volume of adipose tissue increases the apparent volume of distribution for lipophilic drugs and increases their half-life. Everything is pharmacokinetically different, and dosing is made more difficult by the fact that the equations which predict lean body mass and ideal body weight become less and less accurate with increasing BMI. 

Pregnancy results in several pharmacokinetic and pharmacodynamic changes. Oral administration is affected by delayed gastric emptying; distribution is affected by changes in the fat and water content of the body, and metabolism is afected by changes in hepatic blood flow and enzyme activity. Clearance of many substances is increased by the increased glomerular filtration rate. Pharmacodynamic changes are also numerous, eg. increased sensitivity to both local and general anaesthetics. Discussion of adverse effects and dosing adjustments must take into account toxicity to the foetus.

The most important determinants of total blood oxygen content are the effective haemoglobin concentration and oxygen saturation. Solubility plays little role -only about 1-2% of the total oxygen content is dissolved (though this increases with extreme hypothermia). The remaining 98% are bound to haemoglobin.

The College, in their model answer to Question 1 from the second paper of 2014, have constructed an excellent resuscitation protocol, which does not afford this author very much room for improvement.One can merely summarise their model, and expand upon it with references. To be clear, this approach is not "Early Goal-Directed Therapy". Protocolised sepsis management may not be especially effective in reducing mortality (ProCESS, ARISE). Rather than a protocol, this is a stepwise method to tailor a bespoke response to septic shock for individual patients, which branches from simple to advanced management options.

For the patient whose inspiratory flow rate exceeds even the generous threshold of Venturi masks, high flow nasal oxygen is an excellent option. Though the first paper to describe these devices (Dewan & Bell, 1994) gave us this terminology, subsequent authors have occasionally referred to these devices as "high flow nasal cannulae" or "high flow nasal oxygen", because presumably the word "prongs" is somehow uncivilized or intrinsically comical. All CICM trainees will be familiar with the device - it is a single-limb circuit which connects a gas blender to a heater/humidifier, and then funnels a mixture of oxygen and air into the patient, essentially using their respiratory system as a PEEP valve.