From Professor Andrew Davidson MBBS MD FANZCA FAHMS, Medical Director, Melbourne Children's Trials Centre, Senior Staff Anaesthetist, Department of Anaesthesia, Royal Children's Hospital, Professor, Department of Paediatrics & Department of Critical Care, University of Melbourne, Head of Anaesthesia Research, Murdoch Children's Research Institute, Editor in chief, Pediatric Anesthesia, Deputy Editor in Chief, Anesthesiology on the 4-2-1 rule
"Poisonous for children!". That was the label, in large red letters, that started appearing next to bags of "half normal saline" on some Australian children's wards 10 years ago. Since then hypotonic fluids have disappeared from our wards. It has been a slow journey since the 1950's Halliday paper mentioned by Myron. The journey has been controversial and tragic for those children that died due to well-meaning staff prescribing a "poisonous fluid". From the beginning there was doubt that 0.2% saline was the right fluid for children. Some suggested isotonic fluid would be better. Others feared this would lead to hypernatremia. A compromise was reached. We feared going all the way, so we went half-way and half normal saline was born. Alas, children still died from iatrogenic hyponatremia. The medical community couldn't agree on isotonic fluid. The evidence was not quite there yet.
As a researcher we start thinking we will make great discoveries and change the way we care for children; spectacularly improving outcomes. Alas you soon realize that you are lucky if you make one discovery in your lifetime that has any impact - let alone spectacular impact. If you're really lucky you may make two. For me it was the PIMS trial published in the Lancet in 2015 (McNab S, Duke T, South M, et al. 140 mmol/L of sodium versus 77 mmol/L of sodium in maintenance intravenous fluid therapy for children in hospital (PIMS): a randomized controlled double-blind trial. Lancet. 2015;385(9974):1190–1197), though even then "discovery" may be an overstatement. We randomized hundreds of children across the hospital to maintenance with isotonic or half normal saline. The hospital was full of fluid bags wrapped in black plastic. Every ward, every nurse and every junior staff member was involved in the trial. In those days such trials were actually feasible! Sure enough, those with isotonic fluid got less hyponatremia and perhaps fewer nasty complications. Doh... Virtually overnight practice changed across Australia. Trials change practice when we are at the cusp of evidence; just enough to flip things. This was such a trial. We alone didn't change practice, we just gave the final nudge. A couple of years afterwards the American Academy of Pediatrics published the guideline recommending isotonic fluid. (Feld et al Pediatrics (2018) 142 (6): e20183083. https://doi.org/10.1542/peds.2018-3083). Hopefully the "poison" labels are no longer needed anywhere and half saline has gone for good.
One last part of the story. Switching to isotonic fluid didn't completely eliminate iatrogenic hyponatremia. Sick children have elevated levels of ADH, and are at risk of hyponatremia, more so than adults. The 4:2:1 rule is fine for well children but too much water for sick children. We may have got rid of half normal saline but the 4:2:1 error persists; and is still harming children.
From Robert (Bob) Spear MD retired on the 4-2-1 rule
I was fascinated by all things “fluid and electrolytes” in my peds residency in St Louis where I had the pleasure (usually) of learning from one of my best teachers (besides Myron a few years later), Dr. Jim Keating. I appreciate Anne Bailey’s (my med school classmate) advice to only use isotonic fluids in the operating room. There are so many ways to go wrong with hypotonic fluids in sick/anesthetized/mechanically ventilated children.
Here is a list of sodium or fluid & electrolyte lessons that stuck with me.
1. To your chart, you might add “Sodium Concentration of Breast Milk” if you want to stymie 99% of peds residents, PICU fellows or anesthesia folks. The answer is 6-8 meq/L. Yes, 20-fold more dilute than “normal” saline. I know, look it up, that seems too low. Enfamil and baby formulas are similar with 8-10 meq/L of sodium. Here’s a twist, it is not uncommon for newborn infants to become hypernatremic when having difficulty w breast feeding. Why? They simply are not getting much breast milk, so the dilute nature of the milk doesn’t matter…it is remaining in the breast.
2. In the 1970s, the chloride ion was largely ignored because it generally “followed sodium”, whatever that meant. In the category of “The Enemy of Good is Better”, many pediatricians prescribed a new, trendy formula…Neo-Mulsoy in the 1970s rather than breast milk. Fortunately, an astute pediatrician in KC, Stanley Hellerstein, noticed a local cadre of infants who had metabolic alkalosis and failure to thrive despite seemingly taking adequate amounts of this formula. They found that this new formula lacked “chloride”. Much like Myron noting that too much “ab-normal” saline can cause metabolic acidosis, Hellerstein showed that the absence of chloride can cause metabolic alkalosis.
3. Making formula from powder is not without risk. In 1962 in Binghamton, NY, the local newborn nursery had a catastrophic outbreak of seizures and coma. Ultimately, 6 of the 14 infants died. What happened? The formula required the addition of sugar as a final step in formula preparation. Unfortunately, the jar labelled “Sugar” was really Salt. The serum sodiums were as high as 200 meq/L. There is a documentary (“Salt Babies”) which describes these tragic events.
4. Dr. Keating was an astute clinician. Like most children’s hospitals, StL Children’s experienced the somewhat random (to everyone else) admissions of infants with water intoxication that were not all that random. Oddly, they occurred at month’s end…why?…the inner-city mom had run out of money and began to add water to the formula to make it last another day or two until the welfare check arrived the following month. The WIC Program in StL began because of this, circa 1980 and “water intoxication” became much less common.
5. Hypernatremic dehydration occurs in some children with gastroenteritis and the clinical signs often include marked lethargy and always include mild to moderate metabolic acidosis. In the mid 1980s, we had a child present w dehydration, lethargy and metabolic ALKALOSIS. The history from the mother and grandmother did not give us any insight. The following discussion went like this:
Me: “Dr. Keating, we have an otherwise normal formula fed 6-month-old who presents w dehydration, lethargy, poor feeding and has serum sodium of 165 meq/L and bicarb of 40 meq/L.
Dr. Keating: “They must be giving the baby sodium bicarbonate or baking soda”
Me: “I’ll ask again, but I don’t think they are”.
Short story, the baby was colicky, and they were indeed dipping the bottle’s nipple repeatedly into the box of baking soda to soothe the colicky baby.
Breast feeding (even though it is only 1/20 saline) helps avoid iatrogeny.
From Stephan Malherbe, MB ChB, M.Med, FCA(SA), FRCPC, Clinical Associate Professor UBC Department of Anesthesiology, Pharmacology, & Therapeutics, Department Anesthesiology BC Children's Hospital
I must admit I’ve never used D5 0.225% saline, but looking at the table below, the Na+ and Cl- content seem incorrect. The content should be 38.5 mEq/L each for Na+ and Cl- (and not 34 mEq/L each as in the table). Equally, the Osmolarity of D5.0.225% Saline should be 355mOsm/L. 0.2% NaCl will have a Na+ and Cl- content each of 34 mEq/L.
From Alexander Rodarte MD retired
In 2009, I had a handout that compared the solutions for use in the OR. I had to fight the Pharmacy and Therapeutics Committee to allow me to use Plasmalyte outside the heart room because it was a few cents more expensive than NS. Of note was that fact that at the time, it was the common misconception that only NS was compatible with blood or blood products. So at the bottom of my excel spreadsheet that was very similar to yours, I noted the following. "Package insert for Plasmalyte-A injection pH 7.4: The indications and usage section of the package insert of Plasmalyte-A injection pH 7.4 states that the solution is equally compatible to normal saline with blood and components. Plasmalyte-A injection pH 7.4 can be used as a priming solution for blood components, and may be added to or used with blood components through the same line, and may be used as a diluent for blood components."
PS from Myron I received several other emails from readers on this topic/PAAD. I’ve asked our education team to take another look, particularly the articles cited by Dr. Davidson and we will revisit in the near future.
From Ravpreet Singh Gill, M.D. Baptist Memorial Hospital on ACL and regional nerve blocks-To Do or Not To Do?
This is a topic of great interest to me. I have not found a magic recipe yet that results in no opiate use in the post-op period, but my patients do tend to do well now compared to before. In my opinion, the key difference is when I learned how to do IPACK blocks and we started using them for our patients getting ACL repairs. Adductor canal block alone is insufficient in terms of both intra-op and post-op (up to POD 1) opiate use.
It confuses me why some of the people used femoral blocks with their relatively high incidence of persistent quadriceps weakness. I rarely do femoral blocks, and never for an ACL repairs. It also confuses me, based on a conversation that I had with a surgeon, about the use of popliteal blocks. His concern was inadvertent injury to the peroneal nerve during the surgical procedure. He said that is the most common injury reported in their literature and he checks for it in PACU.
I work a lot in a relatively high volume orthopedic surgery center and we have standardized a lot to help facilitate the flow. All of our pediatric patients getting ACL repairs there are 14 and older. I think part of post-op pain control is pre-op preparation for the patient in terms of setting realistic expectations. I make sure to have a conversation with my patients before I do any block. All of our patients get pre-op PO Tylenol. If the surgeon is planning a quadriceps autograft I give them pre-op PO pregabalin and methocarbamol. All of our ACL repair patients get adductor canal and IPACK blocks with bupivacaine 0.5% plain. Intra-op maintenance is inhaled GA via LMA. I think part of the post-op pain may be tourniquet pain in the longer cases, so if the surgeon is OK with it, we tend to give ketorolac towards the end of the case. Our patients rarely need more narcotic than 100 mcg of fentanyl intra-op. In PACU when they are awake the nurses will give them all a 5 mg oxycodone pill. As a general rule of thumb all our patients tend to do great intra-op. A good number go home having only taken one pill in PACU. The mystery is in the patients that are hurting more than expected. But they all seem to be doing well by the time the PACU nurses do the post-op day 1 phone calls. At our pediatric hospital, for the rare orthopedic cases we do there, I have placed the calls myself with the same result.
I know that is a lengthy reply — please trim it as you see fit if you decide to publish it. For the background you asked about last time: I am an anesthesiologist who works in Memphis, Tennessee. I work both in a hospital setting and surgery center setting. I learned blocks in residency but didn’t do them for a long time. Then a colleague, at my previous job in a trauma center, saw my interest and retrained me on ultrasound guided blocks. I am fortunate to work with colleagues who are as passionate about blocks as I am.
PS from Myron: The iPACK (infiltration between the popliteal artery and capsule of the knee) block is an innovative, motor-sparing block that is gaining attention for its ability to target posterior knee pain while preserving motor function, an essential factor for early rehabilitation. Because many of you may be unfamiliar with this block I’ll have our pain team review some of the literature on it and post it in a future PAAD.
From Dr Richard Newton, Consultant Paediatric Anaesthetist, Anaesthetic Sustainability lead, QI Lead APA Survey Lead, University Hospitals Sussex
I was part of the team in 2017 that published using QI methodology to reduce clear fluid fasting times in children ( DOI: 10.1111/pan.13174 ). I then went on to help write the european consensus statement on clear fluid fasting.
The ASA has stated there is not enough evidence to suggest it is safe despite several societies now declaring it so. Our work stems from original data which shows water empties from the stomach in an exponential fashion and is often back to baseline around 30minutes in healthy individuals. When trying to change practice from something which had become dogmatic practice, with little evidence, we had to air on the side of caution and safety. Hence, we felt 1 hour gave us that extra safety margin. It is also been shown that if children do aspirate the sequelae seem to be less severe than adults, with 100% survival quoted1,2. In our study we had 2 aspiration events in 4,828 patients to give an incidence of 4.14:10,000. Whilst we did not have 10,000 patients in our study at the time of publishing there have since been multiple studies all showing the same, no increased risk of aspiration.
As your editorial highlights nicely about the effect of long starvation times on children and the potential harm, how much more evidence does the ASA require? Lets hope the EUROFAST study will put this argument to bed once and for all.
ref;
Kelly C, Walker R. Perioperative pulmonary aspiration is infrequent and low risk in pediatric anesthetic practice. Paediatr Anaesth.2015;25:36-43.18.
Warner MA, Warner ME, Warner DO, et al. Perioperative pulmonary aspiration in infants and children. Anesthes. 1999;90:66-71.