This tutorial looks at the problem of ketoacidosis and, in particular, focuses on diabetic ketoacidosis. Ketones are produced from free fatty acids in the liver, converted to acetyl coenzyme A and oxidatively metabolized for energy production or packaged in the form of acetoacetate or beta hydroxybutyrate and exported to the tissues. This occurs continuously in the body. Control over metabolism is provided by insulin. When insulin levels are high glucose is utilized primarily for energy production and fatty acid metabolism is curtailed. When insulin levels are low fatty acids become the primary source of energy. In situations of very low carbohydrate intake ketones may be measurable in the blood and we call this ketosis. When plasma ketones exceed 3 millimoles per liter this results in a strong ion effect and ketoacidosis. This is generally only seen in states of metabolic failure such as type 1 diabetes starvation and alcoholism.
The ketones acetoacetate and beta hydroxybutyrate are strong anions and cause metabolic acidosis when they accumulate. This manifests as a fall in the bicarbonate and an increase in the base deficit. Classically there is a widened anion gap metabolic acidosis with full respiratory compensation. Nevertheless the extent of the acidosis is rarely explained by ketones alone. Lactic acidosis is frequently present as is acidosis caused by the accumulation of metabolic junk products. Iatrogenic metabolic acidosis may ensue caused by the administration of hyperchloremic (0.9% NaCl + KCl) saline solutions.
Diabetic ketoacidosis is characterized by loss of control of blood glucose, loss of control of blood lipids and hypercatabolism of proteins. Failure to suppress gluconeogenesis within the liver depletes the tricarboxylic acid cycle reserves and results in uncontrolled ketone production. Patients become hyperglycemic glycosuric, keto acidotic, initially hyponatremic, later hypernatremic, and hyperkalemic. The treatment is to fluid resuscitate the patient, administer insulin by intravenous infusion, replenish glycogen stores and provide glucose for intracellular substrate and prevent further ketone production. Extra care must be taken to avoid hypoglycemia and hypokalemia. @ccmtutorials
Proportional assist ventilation has been around in various shapes and forms since the late 1990s. The most advanced current iteration – PAV+ – is unique to Puritan Bennett ventilators. It is a closed loop mode of ventilation. That means that the ventilator dynamically changes the level of assistance that the patient receives in response to patient effort. PAV+ is neither volume controlled nor pressure controlled but is patient (and operator) controlled. The operator adjusts the percentage support that the ventilator delivers to the patient. The patient breathes – triggering the ventilator – and the ventilator amplifies the patient’s breath. Consequently the more work that the patient does to generate muscular effort the more work the ventilator performs to match the patient’s workload.
It has been known for some time that the diaphragm becomes both atrophic and dysfunctional in acute critical illness, in particular due to disuse during control of mechanical ventilation. In most assisted modes, all the patient needs to do is trigger the ventilator. Patient workload may be inversely proportional to ventilator workload. Frequently the patient’s diaphragm and ventilator are out of synchrony.
PAV+ is patient triggered and flow cycled so it should be seen as a form of pressure support ventilation. PAV+ contrasts with standard pressure support in that the degree of support changes from breath to breath and indeed within breath depending on patient effort. Pressure support delivers a fixed airway pressure for every single breath irrespective of patient effort. Consequently if we map patient effort to ventilator workload there is only one point where the two will intersect. Conversely in proportional assist ventilation the workload of the ventilator and the workload of the patient increase and decrease linearly.
PAV+ works by utilizing very high quality flow and pressure sensors. The ventilator determines when the patient initiates the breath and when the breath is completed. Having instructed the ventilator what proportion of work of breathing that the ventilator should perform, one observes, using a work of breathing bar, if the patient is doing satisfactory work or whether they need to increase or decrease their workload. The work of breathing (WOB) is determined by the ventilator by measuring compliance, resistance and intrinsic peep dynamically every 9 to 12 breaths. As such a Green Zone between 0.3 and 0.7 joules per litre is indicative of ideal work of breathing for the patient; I call this the “sweet spot.” As long as the patient’s WOB resides within the sweet spot of the toolbar the bedside clinician can be satisfied that the patient is both comfortable and safe.
As the tidal volume relates to the patient’s neural activity that results in diaphragmatic power one should not be unduly concerned about high or low tidal volumes in this mode.
If one wishes to put a patient on proportional assist ventilation it is imperative that one determines if the patient is breathing spontaneously and taking an adequate minute ventilation prior to using this mode. The reason for this is that there is no backup rate in PAV+. Usually one starts with 70% support: that means 70% of the work of breathing is performed by the ventilator on 30% by the patient. After a couple of minutes, once one has observed the work of breathing bar, one can make adjustments either to increase the workload of the ventilator or to reduce it by keeping the patient within that Green Zone sweet spot. Generally failure of the patient to settle on this mode is manifest by a respiratory rate of more than 35. Once the patient has been on 20% support for an hour or more and is awake, obeying commands, protecting their airway, and not being suctioned frequently then the patient can be extubated.
Studies that have looked at PAV+ versus pressure support have indicated that weaning is more rapid with PAV+.
Lactic acidosis is one of the best biomarkers of acute critical illness, its presence should alert the clinician to a major stress response, where medical and surgical and iatrogenic sources should be considered.
The magnitude and duration of hyperlactatemia (in the acute phase) is predictive of patient prognosis in critical illness. A sustained high lactate reflects a prolonged stress response. The lactate is not the cause or the problem. It is merely a biomarker.
If I were to pick one topic over which I have sweated tear during the past 2 decades, it is lactic acidosis. The problem is that every time I try to explain lactic acidosis, many of those around me become hostile, as if I was committing some atrocity against their religion. And that is because, for the past 100 years, every high school, science, nursing and medical student has been taught that lactate is a waste product that is only made in anerobic conditions. This is 100% ABSOLUTELY completely verifiably WRONG. Lactate, or lactic acid is produced all the time, continuously, in all tissues and is likely the major endpoint of glycolysis. Once produced, it is then either used for oxidative phosphorylation, shuttled to other tissues as a partially metabolized energy source (e.g. the heart and the brain – they love lactate) or metabolized in the liver, principally (the “Cori Cylcle”) – where gluconeogenesis takes place leading to subsequent glycogen storage, fat production or oxidative phosphorylation. As such, glucose is a universal substrate and lactate is a universal fuel.
Lactic acidosis occurs when the production of lactate exceeds the capacity of the liver to clear it. As we produce at least 1250mmol of lactate per day and it is barely measurable in the blood, hepatic clearance capacity is vast. Hyperadrenergic states promote the production of lactate, increase blood glucose and reduce hepatosplanchnic blood flow. The consequence is sometimes called “stress hyperlactatemia” or “aerobic glycolysis.” This is the form of hyperlactatemic seen in sepsis, for example. As such it is an acute phase reactant biomarker – lactate concentration mirrors adrenaline/epinephrine, and should be seen in the same light as CRP, IL-6 and Procalcitonin.
Hyperlactatemia results in metabolic acidosis as a consequence of water dissociation. The strong ion difference (SID) falls. The surplus “hydrogen ions” are mopped up by bicarbonate resulting in a modest fall in pH, but a mEq/L for mEq/L fall in bicarbonate and base excess. Lacate, like Chloride and Ketones, always functions as an acid surrogate and chronic hyperlactatemia is compensated for, usually, by increasing urinary Chloride loss, manifest as hypochloremia.
The terms “Type A” and “Type B” lactic acidosis were introduced by Huckabee in 1961. I believe that these monikers are still useful today. “Type A” represents lactic acidosis associated with blood loss and hypovolemia, intense systemic and splanchnic vasoconstriction, high ejection fraction, low stroke volume and cardiac output and low mixed venous oxygen saturation. Production of lactate increases (and this is multifactorial – not just anerobic), and production falls – due to hepatic hypoperfusion. The treatment is resuscitation, preferably with blood products.
For lactic acidosis, what is not Type A must be Type B – and this represents medley causes (toxic – alcohols), metabolic (end stage liver disease), inflammatory (sepsis), drug induced (metformin and particularly intravenous or inhaled catecholamines).
The term “Clearance” has been used to describe the removal of lactate from the circulation. It is a pharmacological rather than biochemical term, and that has led to some abuse in clinical practice: the belief that “Clearance” can be hurried along with aggressive fluid resuscitation. However, like any particle that is metabolized by the liver, clearance of lactate is determined by the quantity delivered, hepatic blood flow and hepatic clearance capacity. If there is a sustained surge in lactate production, then it may take a while for the liver to clear the surplus from the system while simultaneously dealing with the continued production of lactate by the tissues. In critical illness, we like to see the plasma lactate level falling, but 10-20% is sufficient to be reassuring. A rising lactate is ominous and may indicated inadequate source control or a secondary problem, such as bowel ischemia.
Lactic acidosis may or may not be a marker of tissue perfusion. It is a poor endpoint of resuscitation – and if used as such (the “drive by saline assault”), the result is fluid overload, mutiiorgan dysfunction and prolonged ICU stay.
Sodium Lactate Solutions do not cause lactic acidosis, as they are fully balanced. Most formulations contain a racemic mixture of L-Lactate (which is what the body produces) and D-Lactate (produced by fermentation by bacteria). Blood gas machines do not measure D-Lactate.
This tutorial is about Volume Guaranteed Pressure Controlled (VG-PC) Ventilation – otherwise known as PC-VG, PRVC, VC+ etc. It is a modern mode of ventilation that aims to deliver a desired tidal volume (volume control) using the pressure controlled paradigm (unlimited flow). As such it is a mode that is often labelled “dual controlled” although, in some ways, it is neither volume controlled, pressure controlled nor both. Confused? Most are. I have labelled the mode VG-PC – because that is the best approximation – but volume is not necessarily guaranteed and it is certainly not limited. So why bother using this mode. Simply – it works! As a general use “unit default” mode of ventilation VG-PC has few peers: it is nimble enough to be used as the mode of ventilation of choice for patients admitted to ICU following intubation: postoperatively or with respiratory failure. If the lungs deteriorate – then the mode is versatile enough to deal with it. Being time cycled – mean airway pressure can be easily altered. If compliance or resistance of position changes – then the tidal volume “guarantee” changes the inspiratory pressure from breath to breath to ensure that things remain stable. If the patient breaths spontaneously, using the assist control or SIMV paradigm, flow is increased to meet patient demands. As such it is a very forgiving mode of ventilation, ideal for novices, reassuring to the ICU clinicians. This tutorial explains VG-PC, demonstrates how it is set up in three different ventilators – Puritan Bennetts, Dragers Evitas, Servo I and GE (Aisys) anesthetic machines. I explain the operation of this mode and its strengths and weaknesses. I guarantee you’ll learn something. @ccmtutorials http://www.ccmtutorials.com
This tutorial is about Automatic Tube Compensation (ATC). ATC is a setting that has been included in most modern ventilators. Its aim is to reduce the work of breathing associated with the drop in pressure across the endotracheal tube. The ventilator senses pressure, flow and resistance and changes the pressure during the breath to ensure that the patient has the sensation that they are breathing through their own airway. There are two configurations of ATC – one is as an alternative to pressure support in patients who are essentially weaned from mechanical ventilation: essentially a spontaneous breathing trial. The second configuration is as an accessory to all pressure limited modes – such that the pressure waveform is crafted in inspiration and expiration to reduce the workload of breathing during both phases of respiration. @ccmtutorials http://www.ccmtutorials.org
For most of us, the terms CPAP (continuous positive airway pressure) and PEEP (positive end expiratory pressure) have existed for all of our careers. But this was not always the case. Although mechanical ventilation, including the positive pressure variant, was a child of the 1950s – PEEP was not described until the late 1960s and even then was seen as a therapy for postoperative atelectasis in cardiac surgery patients. PEEP subsequently became the mainstay of therapy for hypoxic respiratory failure, but was always used in associated with positive pressure breaths. CPAP was developed in the early 1980s as a therapy for sleep disordered breathing. Over two decades the non invasive CPAP therapy and the invasive ventilation (pressure targeted breaths with PEEP) coalesced such that CPAP became a therapy for hypoxic respiratory failure and congestive heart failure, and pressure support (BiPAP or NIV) became a therapy for sleep apnea.
Strictly speaking PEEP and CPAP are different. It is possible to apply PEEP at end expiration and then commence the next breath from atmospheric pressure (try slapping your hand over your mouth mid expiration – then remove it and take a breath) – spontaneous PEEP. However this is almost never used in clinical practice. In CPAP the patients sinusoidal respiratory pattern persists – but starts and ends at an elevated baseline pressure. In PEEP the positive pressure breath starts and ends at that pressure (i.e. pre inspiration and end expiration). So, these days, in most scenarios PEEP and CPAP are indistinguishable. How they are delivered is, of course, different. Nevertheless they serve the same functions 1. To overcome airway resistance that causes disrupted or obstructed gas flow in expiration; 2. To reduce the work of breathing by reducing the magnitude of negative pleural pressure required to generate a tidal volume; 3. Most importantly – to restore functional residual capacity (FRC); 3. To prevent derecruitment of vulnerable lung units in the posterior dorsal segments of the lungs.
PEEP does not easily re-expand collapsed lung tissue – this is usually achieved by applying a recruitment maneuver (30cmH2O or more for 10 seconds during anesthesia, for 30 seconds in lung injury). The application of PEEP then prevents derecruitment. As such the majority of lung tissue may be re-expanded during anesthesia. This may not be the case in diseased lungs – the principle is to restore a functional residual capacity even if that effectively utilizes the inspiratory reserve volume.
This tutorial is best experience with a pencil and paper. Before I get into a discussion about high flow oxygen therapy you really need to understand flow. Conventional facemasks, Venturis and nasal cannula deliver modest flows of oxygen to the patient, but to ensure a correct FiO2, oxygen must be blended with air – in the airway or in the device. That air is drawn into the system by entrainment either from the room via the mask or mouth or injected in the case of Venturis into the breathing system. In any case – the inward flow of gas is determined, principally by the patient’s inspiratory effort and the concentration of oxygen during peak inspiratory flow is, hopefully, kept constant. In general, to keep FiO2 constant – a gas flow of at least 30L/min is required. Most devices deliver 40 liters or more, but only at lower FiO2 levels. It is essential to understand that, in this case, the 30 to 40L is NOT high flow – because it is “draw over” flow generated by the patient. High flow, as we will see in the next tutorial is delivered to the patient. For example – when delivering 24% and 28% oxygen to a patient – the total flow may be 44L but the fresh gas flow is only 2 to 4L. The remainder is entrained. This tutorial explains the concept of gas entrainment and how to calculate entrainment ratios and flow rates. If you have never encountered this concept before, I guarantee that you will learn something!
Equations Used In This Tutorial:
The FiO2 vs Flow Equation FiO2 = (Air Flow x 0.21) + (O2 Flow) / Total Flow
The Air:Oxygen Equation: Air/Oxygen = (100% -FiO2)/(FiO2 – 21%)
Oxygen Flow Equation: (Total Flow x (FiO2 -21))/79
This tutorial explains ventilation perfusion mismatch. It will provide you with a platform for understanding oxygen therapy – which I introduce towards the end. I also deal with the concept of oxygen induced hypercarbia. I guarantee you will learn something.
Contents of This Tutorials:
Ventilation-Perfusion Relationships
Gravity and Blood and Gas Distribution Through the Lungs
Gas and Blood Distribution Through Diseased Lungs
Simplistic Ventilation-Perfusion From Dead Space to Shunt
Stale Gas Within Alveoli
Ventilation Perfusion Relationships – Slimy, Soggy and Stick Alveolar Units
Supplemental Oxygen Therapy For Bronchopneumonia
“Targeted Oxygen Therapy”
When Does Oxygen Therapy Fail? [Shunt]
COPD Flair
Why Does Hyperoxia Cause Hypercarbia (VQ mismatch theory)
Clinicians who work in anesthesiology, intensive care or emergency medicine who are involved in the management of respiratory failure must understand the problem of failure to ventilate: “can’t breathe, won’t breathe.” This long tutorial covers a lot of ground and could be viewed in split sessions.
My principle goal is to give you the tools to work the problem of respiratory failure. Along the way I introduce the alveolar gas equation, ventilation perfusion matching and lung volumes; particularly functional residual capacity. In the second half (from 28:20 onwards), I discuss anatomical and physiological dead space, calculate out the dead space to tidal volume ratio and show how you can be inadvertently increasing physiologic dead space by applying PEEP or neglecting auto-PEEP.
Even if you think you know a lot about this subject, I guarantee that you will learn something.
As always, I welcome feedback.
Don’t Be Scared of Respiratory Physiology – it makes sense (well, most of it anyway!)
This is the second tutorial on Volume Controlled Ventilation. I discuss the evolution of ventilators from pure controlled mechanical ventilation, to intermittent mandatory ventilation – with spontaneous breathing to synchronized IMV with Pressure Support. This mode remains robustly popular around the world and critical care practitioners and anesthesiologists should be familiar with the mode, along with its advantages and disadvantages. I guarantee you will learn something. @ccmtutorials
ORtoICU 