In November 2024 six tourists died of suspected Methanol Poisoning in Laos, and several more were hospitalized. Methanol, or methyl alcohol, is an industrial chemical used to thin paints, as a precursor for medley chemicals and for fuel cells. It is passed off as “vodka” (odorless, tasteless, clear) to unsuspecting victims.
Methanol is metaboized by the same pathways as ethanol, but to formaldehyde and formate. Although small amounts of methanol may be found in the body, due to gut bacterial fermentation, methanol poisoning is a life threatening problem. Formate causes a widened anion gap metabolic acidosis, blindness, brain damage and interferes with mitochondrial function resulting in cytotoxic hypoxia.
The treatment for methanol poisoning is fomipazole given 12 hourly intravenously, folate, intravenous fluids and, if necessary, renal replacement therapy. Fomipazole competitively antagonizes the metabolism of methanol by the enzyme alcohol dehyrogenase. If fomipazole is unavailable, ethanol can be given as an emergency measure, intravenously or orally.
Hyperchloremic Acidosis is a common problem. It is usually an iatrogenic problem. Unfortunately, the majority of doctors who cause a patient to have Hyperchloremic Acidosis (HCA) are either unaware of the problem or ambivalent to it. For the most part, HCA is caused by the intravenous administration of isotonic saline solution (NS – “normal saline – NaCl 0.9%). This problem has been known about for more than 100 years and led Alexis Hartmann, a pediatrician from St Louis, to construct a balanced intravenous fluids, that he called “Lactated Ringers” solution. Ironically, in clinical practice, HCA is induced as part of the local hospital “protocol” for management of Diabetic Ketoacidosis. Inevitably, as the ketones fall, the Chloride rises, and the acidosis persists.
HCA is the only cause of “normal” anion gap metabolic acidosis and is almost always caused, . In the tutorial I explain that HCA is caused by a reduction in the Na-Cl strong ion difference (SID). The acidosis associated with NaCl 0.9% is more complex that merely a rise in plasma Chloride. Other serum electrolytes, Albumin and Hemoglobin are diluted – and this has an alkalinizing effect. Other resuscitation fluids have different impacts on acid base. Hyperchloremia is also a feature of Renal Tubular Acidosis (RTA), various other nephropathies, the administration of acetazolamide and other drugs, and following surgical transplantation of the ureters into the small bowel, If renal function is normal, and the Chloride level is lower than 125mmol/L, then the patient’s kidneys will resolve the problem over 36 to 48 hours. If the Chloride is very high, acidosis will persist, particularly in patients with poor renal function, and Sodium Bicarbonate infusions may be warranted.
This is an opinion piece – a rant if you like about the perceptions and understanding of most healthcare professionals regarding the status of Lactate and Lactic Acidosis. It seems to me that everyone has an opinion on Lactic Acidosis, in my own opinion – they are often misinformed. The bottom line is that the body manufactures and processes vast quantities of Lactate each day and that accumulation of Lactate in the blood – Lactic Acidosis – is a sign of acute illness and multifactorial in origin. The Lactate is not the problem. The Lactate will eventually be processed by the liver and kidneys. You need to identify the underlying problem and control the source. Moreover, as Lactate is a signalling molecule and part of a multi-system process for energy transmission (the “Lactate Shuttle”), particularly when there is a lot of white blood cell activity, a raised lactate late in critical illness is frequently a sign of tissue healing, rather than acute inflammation. The biggest problem that I encounter, on a daily basis is the binary belief that hyperlactatemia means global oxygen debt. Certainly it is associated with hypovolemia (which can be identified by capillary refill time and mixed venous oxygen saturation) but more often it is associated with increased catecholamines associated with the stress response. If you are playing lactate-fluid “whack a mole” – each blood sample leads to a fluid bolus, your patient will become fluid overloaded very quickly. The latter is strongly associated with worse outcomes in critical illness.
I make the following points in this tutorial.
Most clinicians overestimate their knowledge of lactate and consider it a waste product of aerobic metabolism. Lactate is likely the end product of glycolysis and a major fuel source for the body. Lactate is always an Arrhenius acid in the body. Lactate is not a good endpoint of resuscitation (“clearance”). Using Lactate “clearance” as an endpoint usually results in excessive fluid resuscitation. High Lactate and Low Glucose is an Ominous Sign. Nobody can be really sure what is in a bag of Hartmann’s Solution (Ringers Lactate). D-Lactate is likely more harmful than you think. There is no specific treatment for Lactic Acidosis.
This is the first tutorial in a new series on acid base balance. This is not a beginners course – although I will attempt to cover everything the bedside clinician should know, particularly in the ICU. I have been teaching and writing about acid base for more than 25 years and I find it disappointing how many clinicians fail to understand even the basics of physical chemistry that underpin this topic.
This course is built on the foundation of physical and electrochemistry (all acid base reactions occur in water, all ionizing processes must be accounted for electrical neutrality must always hold.
The first tutorial is titled “The Power of Hydrogen” and it looks at the chemistry of water, the tendency for water to dissociate into moieties that display hydrogen ions and hydroxyl ions, and how temperature impacts that dissociation equilibrium. It is imperative that you understand that there are effectively no free protons (hydrogen ions) in the extracellular fluid. When we measure [H+] or its corollary, pH, we are measuring hydrogen ion ACTIVITY not hydrogen ion concentration. I explain the origin of pH and how pH varies with temperature despite the aqueous solution remaining chemically neutral. I explain the history of acid base, starting with O’Shaughnessy and then moving on to Arrhenius and Bronsted and Lowry. It is easier to understand acid base if one utilizes the Arrhenius theory, but the concepts are fully consistent with the BL approach, because water is amphiprotic (it can act as a “proton donor” or “proton acceptor.”
I explain how blood gas machines measure pH and why pH (and PCO2) should almost always be measured at 37 degrees Celsius. At the end of the tutorial I explain the terms acidosis and alkalosis, respiratory and metabolic. @ccmtutorials http://www.ccmtutorials.org
Intravenous fluid, fluid management, the physiology of body fluids – all relentlessly controversial and complicated issues. I decided a couple of years ago to put together a course that covers the whole spectrum of fluids – from basic chemistry to basic and advanced physiology, applied physiology, fluid and electrolyte disorders and therapy and acid base chemistry. I will also cover diseases and disorders associated with fluids – either as therapies for, or iatrogenic causes of, disease.
Introduction to the Course
This is a quick introduction to the course, explaining what I am proposing to cover over four parts.
Preliminary Material
This is some really basic chemistry that will allow you to understand the content of subsequent tutorials.
Tutorial 1 Water and Concentrations
This tutorial convers the physical properties of water, what a mole and mmol is and what is g%. I use dextrose as my major example and look at the different ways that glucose concentration is measured in the USA (mg/dl) versus the rest of the world (mmol/L). The end of the tutorial covers the alcohol and calorie content of drinks and drink driving limits.
PART 1 MODULE 1
1 Supplement
I rather like caffeinated drinks and am frequently the subject of sanctimonious comments about my caffeine habit. This tutorial covers caffeine content. Subsequently I look at the issue of 1% versus 2% lidocaine and explain exactly what 1:200,000 epinephrine (adrenaline) is.
Tutorial 2 Salts
This tutorial explains how to calculate out the quantity of electrolytes released from salts as they are dissolved in intravenous fluids. I also take an early look at hypertonic saline solutions.
Tutorial 2 Supplement 1 – More Salt
This tutorial goes through a couple of conundrums where I look at intravenous fluid products and show you how to calculate out the electrolyte contents when you are only given the salts in g/L
Tutorial 2 Supplement 2
This is an early look at calcium supplement products that we typically use in critical care. What exactly is the difference between Calcium Chloride and Calcium Gluconate?
Tutorial 3 Osmosis
Fundamental to understanding how water behaves in body fluids is the concept of osmosis. It is also very important when we visit renal replacement therapies in Part 4 of the course. In this tutorial I use traumatic brain injury and mannitol as my main example.
Tutorial 4 Osmolality and Tonicity
What is the difference between osmolality and osmolarity? What are mOsm? How do you calculate Osmolarity? This tutorial looks at the concept of Osmolality and the Tonicity of intravenous fluids, and why understanding this concept is essential for practitioners of hospital medicine. The clinical scenario is of a patient with hypotonic hyponatremia. I will revisit hypertonic saline solutions and look at the concept of the Osmotic Co-efficient.
Tutorial 5 Electrolyte Distribution
This tutorial looks at the distribution of electrolytes in the body – between the intracellular and extracellular compartments. I look at the needs of a patient who is unable to take oral fluids and electrolytes. I emphasize the importance of maintenance fluids in this situation rather than resuscitation fluids. This tutorial also looks at the interstitial matrix and how it is vulnerable to hydraulic fracturing (“fracking”) caused by intravenous fluids.
This is the end of Module 1.
PART 1 MODULE 2
Tutorial 6 The Adaptive Perioperative Stress Response
Whether we are injured, assaulted or undergo surgery, our bodies respond with an inflammatory response that involves endocrine, metabolic and immune components. The “adaptive” stress response is predictable and its magnitude mirrors the degree of injury. To understand emergency and perioperative medicine and critical illness you must understand the stress response. Having explained the basic physiology, I then go on to discuss fluids and fluid balance and describe the conventional approach (that I do not necessarily subscribe to) to perioperative fluid therapy.
Tutorial 7 Critical Illness and Resuscitation
A patient presents with an “acute abdomen.” His bowel is obstructed and he is losing fluid and becoming both dehydrated and electrolyte depleted. This tutorial looks at the different types of body fluids that may be lost – how they all resemble extracellular fluid and suggests a type of fluid that can be used for resuscitation. I then progress to describing the maladaptive stress response of critical illness, and why it is associated with capillary leak syndrome. There follows a discussion of fluid overload and the need for de-resuscitation. Finally I introduce the topic of chronic critical illness and death.
Tutorial 8 The Macro Circulation
What happens to the body when there is major blood loss? This tutorial looks at the different components of the circulation and how blood flow is redistributed in shocked states. I also look at the assessment of hypovolemic shock, oxygen consumption versus delivery and the mixed venous oxygen saturation. Finally I address resuscitation strategies in acute blood loss.
This ends Part 1 Module 2.
PART 1 MODULE 3 ADVANCES
Tutorial 9 Venous Return
Since the 1970s the venous (and lymphatic) side of the circulation and the right side of the heart seem to have been ignored by doctors. At worst is the widely held belief that central venous pressure represents an appropriate measure of blood volume and resuscitation status. This tutorial looks at the concept of cardiac output versus venous return. I discuss the Guyton concept of mean systemic pressure, the stressed and unstressed blood volume and vascular compliance. I then go on to look at venous return during anesthesia, the impact of low and high dose vasopressors and the impact of fluid overload.
Tutorial 10 The Microcirculation & Capillaries
For the past 125 years or so, the vast majority of clinicians have based their understanding about transendothelial fluid flux on the work of Ernest Starling. Problem is that his hypothesis – the Starling Principle – is wrong. The presence of the capillary glycocalyx and enhanced understanding of fluid kinetics has changed our view of fluid therapy, in particular the role of colloids in treating critically ill patients. This tutorial looks at the capillary network, the traditional Starling method, the “Revised” Starling method, the glycocalyx, oncotic pressure gradients, the impact of fluid extravascation and the lymphatic system.
Tutorial 11 Albumin & Colloids
Colloids, whether they are hydroxyethyl starches, dextrans, gelatins or even albumin, were popular resuscitation fluids until the 2010s. Multiple studies failed to demonstrate the effectiveness of these agents. However, the use of hyperoncotic human albumin solution has gained popularity, based on no real evidence, in recent years. Given our knowledge of the microcirculation, is there any compelling reason to be treating a patient with human albumin solution in the 2020s?
Tutorial 12 Fluid Kinetics
In this last tutorial in Part 1 of this course, we are returning to the operating room. What happens to intravenous fluid once it is injected into the veins a) in normal volunteers, b) during anesthesia, c) during the stress response? This tutorial is all about fluid or volume kinetics and is based on the work of Robert Hahn, from Sweden. I discuss fast versus slow boluses, resuscitation with crystalloid in hypovolemic states, the urinary output during surgery and what happens during hypervolemia.
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ORtoICU 