Autumn 2006 Articles:
What’s Normal About 0.9% Saline?Author: Dr Karen Stuart-Smith, Consultant Anaesthetist, Glan Clwyd Hospital, Denbighshire, Wales.
Intravenous fluid therapy for resuscitation has a long and mainly disastrous history1. In fact, from the earliest times, taking fluid out was thought to me more beneficial than putting fluid in. Blood-letting may have been thought to be curative on the unlikely grounds that pre-menstrual ‘pains’ were relieved by menstruation, i.e. the uterine letting of blood1. Only a man would think that. Whatever the rationale, blood-letting continued enthusiastically until the late 18th Century, when someone finally had the common-sense to review the literature and show that the practice was worse than useless – an early example of evidence-based medicine1.
By this time the principle that the heart pumps life-giving blood around the body had been well established (courtesy of William Harvey). However, it was the cholera epidemics that swept Europe in the early 19th Century that finally demonstrated the life-saving properties of fluid resuscitation. An Edinburgh physician, William O’Shaughnessy, gave the first grim description of the extreme dehydration associated with advanced cholera:
“…on the floor, extended on a palaise… lay a girl of slender make and juvenile height, but with the face of a superannuated hag… the colour of her countenance was that of lead-a silver blue, ghastly tint; her eyes were sunk deep into sockets, as though they had been driven an inch behind their natural position; her mouth was squared; her eyelids black; her fingers shrunk…All pulse was gone at the wrist…”1.
During the course of this epidemic several attempts were made to save lives by the intravenous infusion of fluids. Unfortunately none of these fluid therapies included appropriate ions in the correct concentrations for the simple reason that the physiological significance of extracellular and intracellular salt balance was not appreciated. This would await the studies of Claude Bernard, the father of modern physiology, later in the 19th Century. All of the solutions tried were profoundly hypotonic. The straightforward result of these infusions was that the patients died literally on the end of the needle. As an aside, while researching this article I frequently came across the assertion that Thomas Latta, an assistant of O’Shaughnessy, was the instigator of successful intravenous saline therapy. This assertion does not tie in with the facts. Latta’s fluid contained 58mEq Na, 49mEq Cl, and 9mEq HCO3. The first unfortunate patient to receive this solution died immediately. I hope I don’t have to explain why! Some subsequent patients did survive but were infused with small amounts over several hours. It is likely they survived because the kidney had time to compensate for this ludicrous ‘salinated’ fluid. Eventually the cholera epidemic subsided, and this, combined with the disastrous results obtained with intravenous infusion, caused the subject to be dropped for some time.
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| Sidney Ringer |
Fast-forward to the late 19th Century, and the seminal work of Sidney Ringer, the real father of modern intravenous fluid therapy. Ringer’s papers are classics of their time. Although they read like a gentleman’s guide to scientific experiments rather than a modern research paper, they are of such fundamental importance that they are still relevant today. They have been scanned from the Journal of Physiology and are available free of charge on the internet, so there is no excuse for not reading them2, 3.
Ringer was Professor of Medicine at University College London, but he was also a clinical pharmacologist whose interest was the ionic composition of the blood and the role of these ions in the maintenance of physiological function. He observed the effect of various organic salts on the rate and strength of contraction of the isolated frog heart. His experiments focused on sodium, potassium, calcium and magnesium salts of various types. Ringer’s intention was to create ‘pure’ solutions of individual salts dissolved in distilled water to test on the frog heart preparation, and he was under the impression that the water his lab assistant was using really was distilled. However, it transpired that his assistant was a little dilatory and had been using tap water instead, presumably to avoid the tedious bind of having to distil the water4. In a landmark paper that is the foundation of ‘Ringer’s solution’, Sidney Ringer begins by making a public confession of the error:
“After the publication of a paper (of his)……I discovered, that the saline solution which I had used had not been prepared with distilled water, but with pipe water provided by the New River Water Company. As this water contains minute traces of various inorganic substances, I at once tested the action of saline made with distilled water and I found that did not get the effects described in the paper referred to. It is obvious therefore that the effects I had obtained are due to some of the inorganic constituents of the pipe water.”2.
Ringer immediately analysed the tap water and noted that it contained calcium, sodium, potassium, magnesium chlorine and carbonate, in relative proportion to each other that is not dissimilar to extracellular fluid (although he didn’t realise this immediately). It was also ‘faintly alkaline’, so presumably was close to pH 7.4 (speculation on my part, although other Ringer papers focus on the effect of different concentrations of lime salts on cardiac contraction). The rest of the paper is a meticulous dissection of the effect of different concentrations of these organic salts on cardiac function. The discovery of the cardiac action potential did not occur until the 20th Century, but physiology geeks can see from his results how altering the ionic composition of Ringer’s solutions affected heart rate and force (OK I thought it was fun – your opinion is unimportant). Ringer ultimately defined the ionic composition of a fluid necessary to maintain the healthy regular contraction of an isolated frog’s heart – Ringer’s solution. If you want to know what this was, look at that bag of Hartmann’s hanging above you while you’re reading this.
If it’s Ringer’s solution, how come Hartmann gets the credit? Alexis Hartmann was an American paediatrician whose interest was in the management of severe metabolic acidosis associated with dehydration and sepsis in children5. Hartmann’s papers are also classics and are free to download from the web. Initial experiments (on real patients) demonstrated that the direct infusion of sodium bicarbonate was impractical and dangerous5. Infusion of bicarbonate rapidly resulted in metabolic alkalosis because the only way the body could balance the sudden rise in bicarbonate was through a rise in plasma carbon dioxide via pulmonary hypoventilation and tissue hypoxia – hardly a desirable circumstance. Furthermore, sodium bicarbonate cannot be added to Ringer’s solution as calcium and magnesium carbonates form (i.e. chalk). Sodium lactate is not only stable in Ringer’s solution, but generates bicarbonate at a physiologically tolerable rate, as the bicarbonate is derived indirectly via metabolism of lactate in the liver and kidney. (for the terminally confused, lactic acid is an acid that creates metabolic acidosis. Sodium lactate is the conjugate base and cannot possibly cause an acidosis).
Hartmann wrote a series of case studies on the effect of his ‘lactated’ Ringer’s solution on normal patients and also those with acidosis related to various conditions such as sepsis, diabetic ketoacidosis and renal failure. Many of these patients were gravely ill and died of their primary conditions, which were essentially untreatable in the 1920s and 30s when these experiments were conducted. Further, Hartmann acknowledged that as the generation of bicarbonate from lactate takes place in the liver, patients with hepatic impairment cannot produce useful quantities of lactate from this source. Nevertheless, in several patients metabolic acidosis was corrected and a significant number of lives were saved. As an aside, Hartmann notes in one of his papers that the infusion of lactated Ringers improved acidosis independently of the effect of lactate – an early pre-Schumaker demonstration on the importance of adequate fluid resuscitation in sepsis6. The modern Hartmann’s solution was born.
In complete contrast to the meticulous experimentation and detailed understanding of physiological chemistry that led to the development of lactated Ringer’s/Hartmann’s solution, two currently available fluids intended for intravenous therapy have no evidence base and have been repeatedly shown to be harmful in resuscitation. Of course I refer to 0.9% (normal?) saline and 5% dextrose. In researching this article I have conducted extensive literature searches to try to get to the bottom of why these solutions were made commercially available or why they would be thought to be useful in the face of a complete lack of positive evidence. It has been suggested to me that as house doctors originally made intravenous solutions up themselves in the lab at the end of the ward, these were the simplest solutions to make. As I usually get a small blizzard of e-mails in response to my articles, perhaps someone out there could enlighten me.
To dismiss 5% dextrose first of all, experiments performed more than 40 years ago in dogs with induced metabolic acidosis undergoing sham operation showed that resuscitation with 5% glucose in water resulted in hyponatraemia, hyperkalaemia, worsening acidosis and decreased glomerular filtration rate. Dogs resuscitated with Ringer’s lactate had a normal biochemistry, corrected acidosis and improved glomerular filtration rate7. I’m sure you can work out the physiology for yourself, but the bottom line is that these experiments show that 5% dextrose shouldn’t be given to a dog, let alone a human. ’Nuff said.
So what about normal saline? 0.9% saline has none of the other organic ions (potassium, calcium, etc) that Ringer demonstrated were so necessary in an artificially produced fluid to sustain life. Remember what happened when he said when he looked at the effects of saline alone in distilled (not tap) water: ‘…I found that I did not get the effects described (on cardiac function)…’ (vide supra). Ringer must be spinning in his grave that this defective solution is commercially available and widely used. What does the modern evidence say? Even in healthy volunteers, infusion of 2 litres of 0.9% saline leads to an extremely unphysiological hyperchloraemic acidosis8. How does this happen? It all depends on a guy called SID (the Strong Ion Difference). SID may be defined as a balance between the strong positive (Na+ and K+) and strong negative (Cl-) ions in the body. If a large invasion of Cl- arrives, SID gets upset and starts to produce extra positive ions (H+) to redress the balance. Acidosis results. Saline has a sodium:chloride ratio of 1:1, compared with a ratio of 1.18:1 in Hartmann’s solution. Although this difference may appear small, the result is that volume for volume, infusion of saline presents the body with a much greater chloride load than does Hartmann’s solution, causing a major SID upset.
Saline is retained in the extracellular fluid for much longer than Hartmann’s solution and is excreted more slowly. Diuresis is much slower in saline-infused patients leading to a relative fluid overload. In addition, hyperchloraemia itself seems to have a direct vasoconstricting effect specific to renal vessels, and the glomerular filtration rate is reduced. The upshot of all this is that the kidneys cannot easily excrete the excess chloride, compounding the situation and making SID even more upset. It is worth stressing that these effects are obvious in fit patients having a modest saline infusion. The effects in an already acidotic patient acute renal impairment can be imagined without me having to spell it out. There is nothing ‘normal’ about 0.9% saline.
So why is this stuff commercially available? If it was presented as a new product today, it would not survive a clinical trial, and NICE would certainly never approve it. My view is it should be available in much smaller quantities only useful in clinically justifiable situations. Only then would Ringer be able to rest easy.
But what about Hartmann’s solution? In ionic terms it is far from perfect. The sodium is too high and the potassium is too low. We are relying on a 120-year-old recipe. It needs revising. A good quality crystalloid with favourable physiological chemistry is vital to modern resuscitation, yet no-one out there is doing any research to produce one. The industry (that’s you lot) seem more interested in grossly expensive oxygen-rich fluids for mice in jam-jars. Let’s sort out the basics. Devise a new solution. Pun intended.
References
- Barsoum N and Kleeman C. Now and then, the history of parenteral fluid administration. Am J Nephrol 2002;22:284-9
- Ringer S. A further contribution regarding the influence of the different constituents of the blood on the contraction of the heart. J Physiol 1883;4:29-42
- Ringer S. A third contribution regarding the influence of the inorganic constituents of the blood on the ventricular contraction. J Physiol 1883;4:222-5
- Miller DJ. Sydney Ringer; physiological saline, calcium and the contraction of the heart. J Physiol 2004;555;585-7
- Hartmann AF and Senn MJE. Studies in the metabolism of sodium r-lactate. I. Response of normal human subjects to the intravenous injection of sodium r-lactate. J Clin Invest 1932;11:327-35
- Hartmann AF and Senn MJE. Studies in the metabolism of r-lactate. II. Response of human subjects with acidosis to the intravenous injection of sodium r-lactate. J Clin Invest 1932;11:337-44
- Hutchin P et al. Renal response to acidosis during anaesthesia and surgery. II. The effect of operative trauma on hydrogen ion and free water excretion during metabolic acidosis. Ann Surg 1961;154:145-60
- Reid F et al. (Ab)normal saline and physiological Hartmann’s solution: a randomized double-blind crossover study. Clin Sci 2003;104:17-24
Hitting The Spot First Time With Hand-carried UltrasoundAuthor: Sarah Withington, kdm communications
The advice about ultrasound guidance in the 2002 NICE guidelines on the placement of central venous catheters has led to the increasing popularity of hand-carried ultrasound systems and the more robust systems with better image quality are swiftly becoming invaluable tools for anaesthetists worldwide.
A prime example of this can be seen at the South Tees NHS Trust, in Middlesborough, UK, where several hand-carried ultrasound systems (from SonoSite UK Ltd.) have been purchased for use in theatres and intensive therapy units as guidance systems for vascular access.
Dr Mike Tremlett, Consultant Anaesthetist at the Trust, explained: “Historically, we anaesthetists have relied on anatomical landmarks for central line placement in adults and, for nine patients out of ten of course, the needle goes in first time without any problem. For those one in ten patients where you may have to make multiple attempts to find the vein, ultrasound is excellent. The use of ultrasound imaging has made us increasingly aware of the proportion of patients whose internal jugular veins are abnormal, whether that’s because they lie on top of or behind the carotid artery, whether they have been sclerosed by a previous operation, or are simply congenitally absent.”
In terms of line placement, Mike personally finds ultrasound especially useful for paediatric work and this is certainly a common link with another potential use of ultrasound for anaesthesia, that of regional blocks. “Intuitively, it makes sense to use ultrasound, to be able to physically see the nerve and see clearly where you are putting local anaesthetic and know if you are actually surrounding the nerve with local anaesthetic or not. Undoubtedly the people with the most experience of this are the group in Vienna who have used these techniques in adults, but also increasingly in children for a decade now.”
Mike visited the team at the Neue Allgemeine Krankenhaus (AKH) in Vienna, led by Professors Stefan Kapral and Peter Marhofer, to see their expertise first hand.
Peter Marhofer, who specialises in paediatric and trauma anaesthesia, explained more about the department’s history in this area: “We have been performing ultrasound-guided regional anaesthetics at our hospital for about ten years and are therefore considered to be among the pioneers in this field. Applying blocking techniques to paediatric patients is much more difficult than it is with adults, because the anatomical structures are much smaller, closer together and are, relatively speaking, more vulnerable. Most of the techniques we traditionally used on children were performed ‘blind’, using anatomical landmarks as a guide. The success rates lay between 50 and 80 per cent and, in our opinion, this was completely unacceptable. Using ultrasound, we have the one great advantage of being able to visualise everything we do.”
“To begin with, we made use of larger cart-based systems, but, over time, our research encouraged us to switch to hand-carried ultrasound systems. Their reliability and robust design really impressed us; we now use them on a daily basis and have on occasion used them in foreign countries for research projects, frequently under what might be considered third world conditions, without ever experiencing technical difficulties.”
“Our most up-to-date instruments (SonoSite MicroMaxx® systems) have substantially better image quality and using the newly developed 13 MHz transducers, we are able to examine the nerves that lie close to the surface far better than ever before. The image quality is so good that we have no difficulty whatsoever in imaging nerves that were previously extremely hard to see, to the point that these portable devices are now the only systems that we work with. They also have very good hockey stick transducers with a very small surface footprint of only 25mm, which is so much easier to use when working with children. Having devices like this that are so easy to carry is a great benefit in a hospital as large as the AKH in Vienna. Today, we perform a significant number of central venous procedures directly at a patient’s bedside using ultrasound, moving around constantly, and so a system that weighs only 3.7kg is extremely convenient,” he added.
Mike too has found real advantages in the hand-carried systems he uses: “These systems are simply a joy to use! Everything is so beautifully visible that it doesn’t take long to learn the technique with respect to line placement.” Mike is, however, more cautious when it comes to ultrasound guided regional blocks: “Nerves and regional anaesthesia are a very different business to simple line placement. I recognise that there is a very significant learning curve and I’m looking forward to exploring these techniques more, with the help of my radiologist colleagues. To put things into perspective, you wouldn’t use an anaesthetic machine without knowing the ins and outs and I see no reason why ultrasound should be any different!”
© 2006 kdm communications limited
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Issue: June 2008
