A free online resource for Intensive Care Medicine.
An unofficial Fellowship Exam (CICM Part 2) preparation resource.
Deranged Physiologyis a slowly growing archive of discussions and study notes relevant (or if not relevant, then at least interesting) to the practice of intensive care medicine. The content provides an introduction to the fundamental themes in intensive care: mechanical ventilation, vasopressors, electrolyte management, hemodynamic monitoring, dialysis, and so forth. Attention is directed at equipment in intensive care, and there are attempts to revisit interesting pharmacology and physiology. The aim of this resource is to supplement the bedside teaching of senior staff, and to consolidate resources for intensive care trainees in the initial stages of their training.
The alpha-stat hypothesis suggests we always interpret our blood gases as corrected to the same temperature (normal body temperature) irrespective of what the body temperature actually is. The pH-stat hypothesis instead recommends that we always correct the temperature to the core body temperature. Each approach has its merits and demerits. In order to maintain one's appearance as an intelligent interpreter of blood gas data, one should decide on which approach to use, and come up with some well-articulated arguments as to why one is using it.
The reaction which creates H3O+ and OH- is an endothermic reaction. Therefore, as heat is removed from the system by cooling, the reaction is driven to the left (i.e. in the direction of reassociation) - thereby reducing the concentration of H3O+ and raising the pH. Increasing the heat in the system lowers the pH. In short, the pH of any given solution will change in a fairly linear association with temperature.
Sometimes, one does not wish to be bogged down in elaborate discussions of definitions, or in the minutae of historical developments surrounding a specific concept. Sometimes one only has a ten-minute viva session, or a paragraph in a short answer question to devote to an explanation of pH measurement. For these situations, a brief summary of ABG machine function is available in the "Required Reading" section of the CICM Fellowship Exam Preparation chapters. That, in fact, is enough. The rambling digression on this page certainly does not represent the level of familiarity with ABG analysis expected from the ICU trainee in Australia.
The history of the glass electrode enjoys a thorough and well-developed exploration in a 2011 article by Fritz Scholz, from which much of this information is derived. Generally speaking, the explanation of a concept like this probably benefits from an exploration of its origin, so that the trains of thought can be followed from early observations all the way to the modern era (so that one can understand how the current state of the art ABG analytic technology performs its basic functions).
The modern concept of pH can be defined as a number expressing the acidity or alkalinity of a solution as the logarithm of the reciprocal of hydrogen ion concentration or hydrogen ion activity. This is not the definition. One might search far and wide for a simple lay definition, and one would meet no interesting or informative obstacles for many miles. To uncover a proper definition one must descend into the atmosphere-of-Venus-like environment of Pure and Applied Chemistry. There, one may finally discover the 2002 IUPAC definition, as well as the IUPAC-specified international standard for the procedures of pH measurement.
The original concept of pH was developed by Søren Peder Lauritz Sørensen, and involved the concentration rather than the activity of hydrogen ions. This was the result of earlier work by Svante Arrhenius whose 1884 definition of an acid was "something that dissociates in solution to produce hydrogen ions". In order to precisely measure the hydrogen ion concentration without resorting to colour-change tests, Sørensen devised an experiment in which the concentration gradient of ions could be related to the electric gradient between electrodes in an electrochemical cell.
Since Arrhenius started being taught in schools, and since most people started going to school, the concentration of hydrogen ions became a household term, synonymous with pH. Even as Sørensen revised his definition in terms of activity rather than concentration, people were taking up the notion that in every glass of water, some 107 protons and hydroxyl ions were lurking, free and naked, ready to tear molecules to shreds. Plainly, this is insane.
The IUPAC definition incorporates both the Brønsted and the Lewis models of acids and bases. Thus, an acid is "a molecular entity or chemical species capable of donating a hydron (proton) or capable of forming a covalent bond with an electron pair." The two models are complimentary, and coexist easily in the complex minds of chemists, as they are useful for different situations.
According to Svante Arrhenius, an acid is any substance which contributes hydrogen ions (H+) to the solution, and a base is any substance which contributes hydroxide ions (OH-) to the solution. This definition was the result of early research by Svante Arrhenius whose 1884 doctoral thesis concerned the dissociation of electrolytes. The research and analysis had ultimately earned him the Nobel Prize for chemistry in 1903. This century-old definition is actually the definition one will get when one walks around asking random medical staff to define what an acid is. Unfortunately, as a definition it has several crippling flaws.
The acidity of your precious bodily fluids is a carefully guarded parameter. To allow this parameter to deviate out of a very narrow range would massively impair your capacity to continue living. Basic molecular services would break down. Cellular anarchy would ensue. In order for the ICU physician to wrest a form of order from this chaos, a reasonable grasp of basic acid-base chemistry is expected. An excellent medically themed foundation for acid-base chemistry is laid by Kerry Brandis in a highly acclaimed series of online articles, to which I will constantly refer. It is not my intention to supercede this resource, as it remains canonical for all critical care trainees.
Lets face it, we don't really care about venous oxygenation (or arterial, for that matter). The real issue is how much oxygen is in the cells? How are those cells using it? The intracellular environment is a place of massively heterogenous oxygen demands. Some organelles are involved in enzymatic metabolism of drugs or maintenance of electrolyte gradients - these areas require a higher oxygen tension than, for example, mitochondrial ATP synthesis.
Central and mixed venous blood gases offer us a glimpse of whole-body oxygen extraction.
A mixed venous blood gas is a sample aspirated from the most distal port of the PA catheter, offering a mixture of inferior vena cava blood, superior vena cava blood, and the coronary sinuses. Thus, the result is an average of venous blood. But what if I don't have a PA catheter, you might ask? A central venous gas may be almost as good.
Dobutamine is a synthetic catecholamine. As well as a well-defined catechol group, it possesses a humongous amine substituent group, which confer upon it a high level of beta-1 selectivity. This is the result of "intelligent drug design". The first paper to describe its properties (1975) is an amazing piece of work. The authors systematically produced a whole bucketfull of catecholamines with different side chains, amine substituents, hydroxyl group arrangements, etc etc - and then tested them for cardiovascular effect. Indeed, much of what we know about the structure and function relationship of catecholamines comes from such experiments.
This chapter is a summary of the pharmacological properties of milrinone. My main focus will be the differences between milrinone and dobutamine. These are the two major old-style inotropes in our arsenal; and there are situations which favour the use of one over the other.