So hello everyone and thank you very much for joining me while I discuss the very thankfully rare acute tumour lysis syndrome. So in the 10 years that I've been working in the oncology service at Northwest Veterinary Specialists, I have only seen this happen twice out of the hundreds of cases, possibly thousands of cases that I've actually, dealt with and administered chemotherapy to. So thankfully it is quite rare, but when it does happen, it, it can be catastrophic.
So what is acute tumour lysis syndrome? So this is just a little bit of a brief overview initially before I go into the full detail a little bit later on. So this is a spontaneous or radiation or chemotherapy induced rapid lysis of malignant cells.
So as these malignant cells are destroyed, the intracellular contents then spill into the systemic circulation. And this exceeds the renal and hepatic excretory mechanisms. So this leads to a life threatening metabolic and electrolyte disturbances and then a renal renal dysfunction or an acute kidney injury.
And this is a true oncological emergency. So I just want to add that this is actually, this is different to mast cell degranulation, which is the release of heparin, histamine and enzymes following the manipulation, chemotherapy or radiation treatment of a mast cell tumour. So it is different to that.
I just wanted to add that in. Hm So who's likely to be affected with this, this awful syndrome? It has been well recognised, .
In human cancer patients, and it does tend to be patients that have a haematological malignancy that are at higher risk compared to patients that have a most, well, most solid tumours. So these are the cases such as lymphoma and leukaemia as they are super sensitive to the effects of chemotherapy and radiation. So who's who is at risk?
So it is patients as we've discussed, with a haematological, neoplasia and these guys that have got advanced disease and a large tumour burden. So these high grade lymphomas, these acute lymphoblastic leukemas, there was 11 report that he found that it was a dog that had a thymoma that had radiation treatment. These dogs that these tumours that have a high proliferation fraction, and so this just shows that this tumour is active, actively dividing and that it is a more aggressive tumour.
So patients that have abdominal involvement, so these lymphomas, these multicentric lymphomas that have hepatic and splenic involvement, and if there is a pre-existing renal disease and dehydration as well. So for the pre-existing renal disease, this can increase the risk factor. Renal clearance is a primary mechanism for excretion of phosphate, potassium and uric acid.
So if these guys have got a pre-existing renal insufficiency or dehydration, they're not able to cope with the excretion of, of those above components. So a 2006 paper had identified and listed . Kind of a four components that could be.
That that increased the risk factor for developing acute tumour lysis syndrome and this was, the first one was body weight loss. So over a 10% body weight loss prior to the start of treatments, prior to the chemotherapy being administered. This is because it's indicative of an advanced disease, an increased tumour burden, or that this patient, patient is also, is already Struggling with cancer cachexia.
As I mentioned, just if this patient has already got some renal disease or a chronic kidney disease, this is because there is an impaired ability to excrete the phosphate and potassium. If this patient is then initially treated with with L asparaginase for these lymphomas and leukemias, this is because this treatment is highly effective against lymphoma and it does actually cause a rapid cell lysis. So one of the cases that I dealt with did have L as L aspar administered and I'll just mention her in the next slide.
So yeah, this is an increased risk factor. And then the presence of a meta metabolic acidosis prior to administration of chemotherapy, as this emphasises it's systemic impact of meta metabolic abnormalities. So findings suggest that dogs that have got one or more of these risk factors require an increased monitoring during chemotherapy and definitely in them hours, 1224 hours or so after chemotherapy, we should be keeping a good close eye on these.
So when can it happen? So what I've done, I've I've just kind of put a little table together and after I'd went through a couple of papers that I'd found, and then two of the cases that I'd actually dealt with in hospital, so this first study, which was from 1998, showed that there were three dogs that had lymphoma. Two of these patients, two of these three patients had half body radiation.
And the onset of signs, clinical signs for acute tumour lysis syndrome actually started within 18 hours to 8 days after treatment. And then death occurred for the 3 of these guys within 6 to 18 hours after the onset of signs. A 2007 case report of a Scottish terrier with lymphoma who had had disease progression initially after she'd responded well to chemotherapy.
She had whole body radiation therapy and her signs, Started 4 hours after her first treatment and thankfully she survived . I've survived all of that. There was a tooth and then there was another case which was a 2 year old female neutered cat, which had lymphoma, and she was FELV positive as well.
So she had L asparaginase, intraperitoneal and prednisolone, and there was actually a really poor response to that, so, She then had adjunctive radiation therapy as well, and she developed her clinical signs 7 hours after the radiation therapy, which was about 55 hours after the initial L. Sparaginase treatment had been administered. And she actually survived her event as well.
So these two are our cases that we dealt with in hospital and Charlie, I'm going to go into a little bit more detail later on. He had a partial response to CHO and he had 8 treatments but was kind of like a partial response and then started to progress. So we gave him some Espar and then 3 days later we gave him the rabbitrosidine, which is the Tanovia.
And his sign started at home probably about 6 hours later, but the owner opted to monitor him at home just because he was, they were quite a ways away from us. And yeah, they just, he, they've given him some more serenia and some paracetamol and they said he, he actually seemed a little bit better. And unfortunately he actually crashed, within the hospital about 41 hours after we had administered his chemo.
Then we have little strawberry who was a Tibetan mastiff with a multicentric lymphoma, and she did have hepatic and splenic involvement with her lymphoma. So she was administered L asparaginase subcut about 6 o'clock one day, and her clinical signs started approximately 12 hours later. She was, she was quite a quiet dog anyway, and she was quite a large dog and was kind of feeling a bit a little bit rubbishy anyway.
So her blood's about 13 hours after the LSPAR administration showed that she was hypokalemic, hypocalcemic, and had hypophosphatemia as well, and she crashed about 14 hours after the administration. So the signs can start most commonly within about 48 hours of administration. So what happens, we administer the treatment, either the chemotherapy or radiation treatment, and this causes a rapid lysis of these malignant cells.
So these release the intracellular contents into the systemic circulation and these contents are the phosphorus, potassium and purines. So once they've all been released, this can actually then overwhelm that renal excretion mechanism. So with the phosphate, I said these malignant lymphocytes contain about 4 times the amount of phosphorus compared to normal lymphocytes.
So then we come along, we give them some chemotherapy and all of these malignant lymphocytes with the 4 times the amount of phosphorus lies, so it does actually then lead to a profound hyperphosphatemia. This then leads to a subsequent hypokalemia due and then this due to the precipitation of calcium phosphate in the tissues including the renal tubules, so this can actually then lead to an oliguric or aneuric acute renal failure and also a subsequent hypokalemia as well. There's hypokalemia, .
Can lead to some neurological complications, so of the total circulating calcium, about 40 to 50% is protein bound, so and then 40 to 50% is ionised, and then another 10%, Is complex with other substances, so it's only the ionised calcium that is actually available to tissue for tissues to use. So when this calcium starts to become low, it can start to cause a disruption of the stability of the neuronal membranes, making these neurons hyperexcitable and prone to spontaneous depolarization which can start to trigger seizures. So this low calcium also affects the calcium channels in the brain, further destabilising the electrical signalling.
And then tetany is a medical condition characterised by involuntary muscle muscle contractions and spasms also caused by the hypocalcemia. So as we've mentioned these, as these tumour cells start to break apart, the major intracellular cation is potassium. This actually then moves again into the systemic circulation, leading to a hyperkalemia which is then progressive.
So you know the hyperkalemia can cause a lethargy, weakness, bradycardia, syncope, and then some life threatening cardiac arrhythmias as well. So they So this hyperkalemia can cause a prolonged PR interval, a decreased R wave amplitude and increased T wave amplitude. This then progresses to atrial standstill with a widened QRS complex and bradycardia.
This sine wave can sometimes be seen shortly before asystole, and any patient that has a potassium over 7.5 millimoles per litre is a concern. And severe hypoglycemia also can cause some ECD ECG changes and a prolonged QT interval and hypertension as well.
So with the purines, so haematological neoplasms have a high nucleic acid turnover because of this increased DNA synthesis requirements. So lysis of these cells leads to a hugely high concentrations of purines leaking out into the peripheral blood. So in humans, purines are metabolised by the liver through oxidation of hypoxanthine and xanthines into the end product, uric acid.
So that as this serum uric acid concentrations increase, this uric acid becomes less soluble, enabling the formation of crystals in the renal tubules, and this can actually then lead to an acute renal failure. So with dogs what actually happens with the like I said with the exception of Dalmatians and English bulldogs, er these oxidise the uric acid to alatonin in the liver via the enzyme uricase. So this is this, this difference is what actually then prevents most dogs developing this hyperuricemia, but in theory, Dalmatians and these English bulldogs are more susceptible to er the acute tumour lysis syndrome associated hyperuricemia because of these dogs lack that uricase enzyme.
So there is mention of the possible use of allopurinol to decrease the formation of uric acid by blocking the conversion of hypoxanthine to xanthine and then the xanthine to uric acid and then therefore no crystallisation, but I think I kind of seen this mentioned, but it's not something that we, I think actually did for our patients as it's it's something that's probably not really expected to happen in dogs. I just wanted to mention it. So OK, a quick recap, I'll do this a couple of times throughout, so we are, we are gonna lead to a hyperphosphateemia and hypocalcemia, and these, that can then lead to an acute renal injury.
The hypocalcemia can start to lead to some cardiac arrhythmias, neurological symptoms and seizures. The hypokalemia can lead to the lethargy, weakness, bradycardia, syncope and some life threatening cardiac arrhythmias. So in one of the papers, there was an increase in total bilirubin.
And this was a patient that I had, whole body radiation therapy, and they wonder whether or not this, this elevated total bilirubin was due to an inflammation induced choliostasis, possibly due to the effect of this inflammatory mediators on bind salt bile binding to the hepatocyte. So these patients can sometimes are likely to end up with an acute kidney injury and this is like due to potentially hypovolemia. The uric acid precipitation in the ureters and distal renal tubules, unlikely due to this, but I wanted to mention it again.
And then most likely due to the hyperphosphatemia leading to hypercalcemia due to this precipitation of calcium phosphate in tissues, including the renal tubules. Metabolic acidosis is also a complication, so there is a high rate of tumour glycolysis so the high rates of tumour glycolysis produces lactate as a byproduct, and this impaired hepatic uptake and or renal excretion of lactate is what can then cause a meta metabolic acidosis. Oh, obviously, DIC wants to get involved as well because why not?
So yeah, we, as we know, it triggers for DIC, shock, neoplasia and systemic inflammation. And we've just caused also all manner of carnage to this poor body system. So then this, we know that it is going to lead to prolonged clotting times, thrombocytopenia, hypoalbuminemia, and this is likely secondary to capillary leakage and hemodilution.
And we're looking for these visual signs of kind of petechia or bleeding from like any blood sampling sites or IV sites as well. The the dog in the paper that the 2007 paper that had whole body radiation therapy for his lymphoma actually did develop and survive DIC. All these papers are all very interesting to read.
So death can occur, a lot of our, the two of the two of our patients that we dealt with both did end up crashing, and we elected to, well obviously there was, there was no CPR for them, but euthanasia should be discussed with the owners. And death does tend to occur because of the cardiac complications, the severe hypocalcemia and hyperkalemia and the acid-based status as well leading to this multi-organ failure. So to diagnose the acute tumour tumour lysis syndrome, the Cairo Bishop definition of acute tumour lysis syndrome is an assessment of laboratory results and clinical signs.
So for the lab lab diagnosis, they need to meet two of the four criteria. And this is an elevated potassium, hyperkalemia, hyperphosphatemia, and hypocalcemia. And then for the clinical signs, so what I've highlighted in blue is part of is the is what they are looking for for the criteria.
And this is reached by confirming that the the lab criteria already plus one or more of the clinical signs, so the creatinine, which is 1.5 times the upper limit of normal or the patient's baseline. And for that we're gonna be seeing an AKI and then an aura or oligura as well.
We're gonna be seeing some seizures which has come from that hypocalcemia and then cardiac arrhythmia or sudden death because of that hypocalcemia or hyperkalemia. As well. So once we've started to get more than one of 3 of these plus the lab sam, the lab results, this is when we can then diagnose an acute tumour lysis syndrome.
We will also be seeing weakness, lethargy, pyrexia, GI signs, shock, and then the petechia and as I mentioned before, DIC2. So if we do have a suspicion of acute tumour lysis syndrome, we are gonna want to examine this patient and do a full clinical examination. So patient's demeanour, we're probably gonna be seeing these guys are are quite flat, they're dull, lethargic, .
Very different to what we would have expected that patient to be, the patient that I'll discuss later on, actually when he had his chemo was as really, really happy, really as bright as a button, then when we saw him the following day he was completely different. Are likely to be pyrexic, we're gonna be looking for heart rate and pulse quality, respirating effort, thoracic auscultation, and the mucous membrane cola, and refill time. We want the body weight and we want to assess them for any petechiae or bruising as well, so kind of like on the, as you know, on the gums or on the abdomen or pretty much anywhere that we could see, or if there's any evidence of any leak blood leaking from any previous IV or blood sampling sites.
So if we're starting to get a little bit suspicious for this guy, we're gonna want to start running some bloods. So we would want some blood gases cos we want to assess the bicarbonate concentration, and the patient's blood pH. We're gonna go straight for biochemistry and electrolytes.
We want the urea, creatinine, the potassium, calcium, phosphate and albumin. So if the urea and creatinine are within normal limits, this will support that the hyperphosphatemia and hyperkalemia is acute tumour lysis syndrome rather than secondary to an acute ura or an acute kidney injury. So we will also be looking for a haematology as well to assess the platelets and neutrophils to see whether or not DIC is in fact starting to set in yet.
And then we'll look for coagulation as well, again for the DIC factor as well. We have an epoch machine, so this is something that we will repeat regularly for our what we repeated regularly for our patients, because that kind of covers our bicarb, PH, urea, creatinine, the ionised calcium and the potassium as well, and then we could add in anything else that, else that we wanted to monitor as well, but the epoch was kind of like a, One covers all and only a small amount of blood was needed. So to treat these guys we're gonna want some fluid therapy, we're gonna any correction of hypovolemia so that and also then to maintain hydration.
So we want a diuresis ideally with sodium chloride, usually about 2 to 3 times maintenance. This is so we can actually then maintain adequate tissue perfusion, therefore alleviating vascular status, stasis, tissue hypoxia and acidosis as well. We're gonna monitor that urine output and if we can place an indwelling urinary catheter so we can monitor er what that patient actually is starting to produce because as that hyperphosphatemia and hypocalcemia starts to progress, and then they start to er start with that acute kidney injury and then urine or output production will actually start to form.
So we monitor the fluids that are going in, so any water or fluid therapy and any fluids coming out as well. We're gonna want to correct any biochemistry and electrolyte abnormalities, so there's hyperkalemia. We can use dextrose alone within the fluids as this stimulates insulin secretion to promote the intracellular shift of glucose and potassium, therefore reducing, reducing the potassium.
We could potentially add in some neutral insulin and then alongside some glucose as well as this promotes a glucose shift without having to rely on the endogenous secretion of insulin. And that 2007 case report showed that that patient's hyperkalemia just resolved on its own when they were on quite a high fluid rate of 5.4 mL per kilo per hour.
Hypercalcemia can be corrected using IV calcium, and this is to reduce the patho can also help to reduce the pathologic effects of hyperkalemia by antagonising the effects of potassium on the cardiac and other cell membranes as well, and it will help to correct that hypocalcemia and hopefully then correct any neurological signs that are occurring as well. And then hyperphosphatemia we would use er that dextrose and this facilitates the intracellular movement of the phosphorus, therefore reducing the phosphorus. So if this patient is meta has a metabolic acidosis, we can use a sodium bicarb to correct this and this can help to correct the hyperkalemia as well as it can cause movement of the potassium back into the cells.
So for treatment of DIC we're hope if this patient does end up with a DIC hopefully we can we. The treatment for DIC is fourfold, so hopefully we can, we're gonna, we're gonna start, we're gonna be doing the 1st 2 or 3 anyway, by correction of the underlying cause so we know what's already going on with this patient, so hopefully we're already starting to control what's going on. We're gonna optimise perfusion so this patient's gonna have appropriate fluid therapy and this is then to prevent any further renal and GI ischemia and prevention of any secondary sepsis as well.
We're gonna prevent any secondary complications, so hopefully this is what we're already doing by correcting the acid base and electrolyte abnormalities and then potentially give some oxygen supplementation if needed. And if there's any hemostatic defects starting to happen as well, we can administer any fresh frozen plasma because that can provide any antithrombin and replace any depleted coagulation factors. If that patient is actively bleeding, we're gonna be looking at using some whole blood or packed red blood cells, coagulation factors and platelet as it sorry as the whole blood because it contains the red blood cells, coagulation factors and platelets.
And the use of antithrombotics is rational, but we should, we should be closely monitoring these patients if we do stop to use these. We are going to want to be looking at . Symptomatic treatment for these guys as well, so any vomiting and nausea, these guys are gonna be feeling pretty rubbish, and we're going to be needing to use, meropotent, metoclopramide and Dondansetron, and quite commonly we will use all three together, and we'll administer these IV because their oral administration is, it's not going to be readily taken, and we want to make sure that they're actually able to, to utilise what we're giving them.
Diarrhoea as well, we, I said, we use a smectite clay now if there's a chemotherapy induced diarrhoea, but whether or not, we can add in probiotics and if required, we can use some rescue an antibiotics if there is any haemorrhage in there as well, but probably the main one that we need to be controlling is the vomiting and nausea for these guys. If they're kind of getting through the original crisis and we start needing to look at nutrition for them, obviously we're going to be looking at aiming for the RER when I read through some of the papers, the guys that were surviving actually started eating well on their own after they got through that crisis. Or eating well on their own, so hopefully they would start to eat on their own, but you could actually consider placing a nasoesophageal feeding tube, and the, make sure that you are controlling any vomiting and nausea as well.
We could add in appetite stimulants as needed, er, but again, making sure that we've controlled any other factors that might put that patient off wanting to eat, mainly the nausea and vomiting. And we can use the mirtazapine or capammorelin which we can get now with an SIC. So for the, looking at some nursing care for these guys as well, these, a lot of these guys are gonna be quite flat, probably.
Yeah, not, not, we're gonna need quite a lot of intense nursing care or will need a lot of intensive nursing care, so we look after these guys' eyes because these critical patients have a reduced tear production and blink, so it's an increased risk for corneal ulcers and infection. We're gonna be looking at keeping their mouth nice and healthy by keeping their tongue in their mouth to prevent it becoming dry and swollen. And you can use a damp swab over the tongue and gums as well just to prevent them becoming dry.
Recumbency for these patients should, they should be turned every 4 hours and we can place a pad in between the thoracic and pelvic limbs as well just to avoid any extra strain on the joints. If these guys have got any long hair, we're gonna clip away at that and clean away any urine and faeces to avoid any soiling and place a urinary or faecal catheter and collection bag if we can. So we're an ident we need to identify our high risk patients and kind of put some preventative measures in place so.
With, with this is with close monitoring and hospitalisation and scheduling some bloods and monitoring . As they are hospitalised, so we need to, so we'd identify these patients that do have a highly treatment responsive tumour, with a high tumour burden and if they have got abdominal disease as well. Is there any pre-existing dehydration, renal insufficiency, hepatic dysfunction, hypercalcemia of malignancy.
So we should be correcting all of this before we've administered the treatment ideally. So we could get some fluid therapy going before they've started the treatment or even start at the time that they have that first chemotherapy, and we'll correct, any dehydration, electrolyte, and, changes before we've actually administered that chemotherapy. And then we want to be monitoring their electrolytes, renal values, hydration and demeanour quite closely as well.
So the last patient that we were pretty concerned about was a gorgeous little patient called Jet who had a, has a multicentric lymphoma with splenic involvement. So his renal values and everything were pretty were fine prior to administration of Vincristine. We opted to hospitalise him because he did have quite a large tumour burden with abdominal disease.
We administered his Vincristine, gave him fluid therapy post chemotherapy. So we were going to hospitalise him overnight on some fluids. We opted not to start his steroids at that point, with the chemotherapy.
We wanted to kind of make sure we didn't cause him any complications immediately after the Vincristine. So we, as we hospitalised him overnight, scheduled him for a blood epoch blood test the following morning so we could assess for his potassium, urea, creatinine, ionised calcium, pH and acid base status, that following morning just to make sure everything was OK. But the overnight team had instruction to run an epoch, sooner if there were any concerns.
And the following morning, his epoch was absolutely within normal limits and he was as bright as a button, thankfully. And then we were able to then go ahead and start his steroids that day. As I mentioned before, it's important to get a CPR status from the owner and make sure that it's clear on that patient's hospital sheet and that everyone knows what the plan for that patient actually is.
If the owners are actually wanting CPR, make sure that you've got the drugs and doses all ready, make sure you've got an airway kit and oxygen and monitoring all ready to go. This patient's, if it's kind of getting to that point, he's likely already on your monitoring, so you're kind of keeping an eye on that ECG and providing some oxygen. And if they are, they've requested no CPR can we assist that patient if they do start to crash, er, can we administer some euthatal or something if they are crashing?
And euthanasia is, unfortunately one of the definitely one of the outcomes as I've just, just discussed for this, . For this terrible syndrome, both of the patients that we dealt with er. Did end up crashing .
But we're reading through some of the other papers that a couple of the patients did actually survive through all of this, so I think again it is just patient dependent and how they are actually responding to treatment and the severity of the original signs. So I just wanted to run through one of the cases that we dealt with at Northwest Veterinary Specialists. And this was a gorgeous little beagle called Charlie, he was 5 years old and male neutered.
So he'd been diagnosed on. The 3rd of November 2023 with stage 5 B cell lymphoma. We initiated treat with the multi-agent protocol CHOP.
So he had his first cycle over 4 weeks. So we had the Vincristine, cyclophosphamide, Vincristine, and then epirubicin. And at the end of the cycle one, his lymph nodes are still enlarged and firm.
They weren't as big as they had been initially, but they were still giving us a little bit of concern. We opted to continue with cycle 2, but to increase the doses as he tolerated the initial lot of doses, initial 4 weeks really well, so we opted to increase them. And give him the benefit of the doubt, see how he responded with, over cycle two.
But by the time we got to 7 days post eppirubicin, so we're kind of like week 9, 10 now into chemotherapy, all of his lymph nodes were actually larger, so indicating, a failure of the protocol with the disease progression. So he was seen by his primary care clinician for lameness on the in the early January, and he was given meloxicam. And on the 12th of January, he was seen by us because he had hemorrhagic diarrhoea following the meloxicam, and so that we discontinued this and started gabapentin and paracetamol.
He had also progressed again with his lymphoma, so his lymph nodes were actually larger again. So we, what we needed to do was kind of we needed to, I think we were just giving him letting him get over the hemorrhagic diarrhoea before we then went ahead and wear any further chemotherapy and steroids for him. So on the 13th of January, he was seen out of hours because he, his lymph nodes were enlarged again.
And he had some L asparaginase administered, It was noted that when he came back a few days later, there was actually no response and possibly some progression following the ESA administration. So he came on on that 16th of January and we administered Tanovia to him and we started his steroids as well. So yeah, on that 16th of January, the Tonovia was administered probably mid-afternoon.
He was really bright and happy on that day. He was generally really well otherwise. He was like he, his lameness was kind of under control.
He was feeling pretty good and he was generally a 5 year old beagle, a male male beagle, he was actually just quite a happy little, happy little soul. So the owners called us out of hours and spoke to one of our part of the night's team about 10:30 as they've noticed that Charlie was a little bit, was a lot quieter than was quieter than usual. He wasn't really eating given he was a beagle.
It was completely out of character for him. And he was trembling a little bit. They've given him his Cerenia at 9:30 and his gabapentin and paracetamol.
So by the time they called us at 10:30, there had been some improvement in him. So they opted just to monitor him at home and as they lived probably about an hour, a good hour or so away from us, so they wanted just to kind of see how he was. They just touched base with us, they wanted to just to kind of let us know.
They're going to see how he was and then they would come, call us or come to see us if they were concerned. We did advise that it was potentially a tumour lysis syndrome, but actually, but actually let's see how we advise regarding the tumour lysis syndrome, but being that he'd actually started to feel a little bit better, and we opted just to kind of let him carry on, let them see what, how he was over the next couple of hours. He was seen then the following morning by his primary care clinician or I think it was kind of like maybe morning, early afternoon-ish by the time he was seen there.
So he was PUPD, he was vomiting, he was very lethargic. His temperature was 38.8, heart rate was 140, and he had a ventral edoema.
In-house bloods, we were, so we spoke to his primary care vets, and we asked them to kind of check everything for us. So his biochemistry revealed that he was azoemic. His total calcium was, low, low, just, just below the low end of normal.
So he was hypocalcemic. He was also hyperphosphatemia hyperphosphatemic. And here we we asked them to do a pancreatic lipase snap test as well.
And this was normal and we asked them to do this because he'd had L asparagidase a couple of days before and L-spar has been shown to cause pancreatitis in some patients. So we wanted to make sure that it wasn't just, Not just pancreatitis, that it wasn't pancreatitis, before we, commenced with everything else. His one, but that actually was that normal.
And so his potassium was 5.4. So this was at the high end of the reference range.
So it was just about still within normal limits. But it was, sneaking up there. So the primary care vets placed an IV, gave him some ondansetron because he was vomiting.
And then he was sent straight on over to us as an emergency. So he arrived with us probably about 6:30 and we did all of his bloods. His clotting times were within normal limits.
His ECG was unremarkable. We did an A fast on him. There was no abdominal free fluid and we checked his bladder size, and it was 3 by 5 centimetres.
And this was just allowed us to monitor his bladder size and urine production during due just because of that risk of the oliguric auric AKI. His blood pressure, his mean was 66.5, so it's kind of sneaking down there.
We wanted to place a urinary catheter so we could monitor his urinary output. We weren't, but they struggled to actually place one because of this ventral edoema, so we weren't actually able to place one in him. So we administered dex so by the time he got to us, so yeah 7 o'clock we'd run some bloods and his phosphate was 5.2.
His ionised calcium was 0.78, so this was low. His potassium had then snuck up to 5.7.
His lactate was elevated, and he was azotemic and acidotic as well. So we administered dextrose alongside his Hartman's solution, and we did that, as I mentioned before, this is to facilitate the intracellular movement of phosphorus, . Therefore reducing the phosphorus and it also stimulates insulin secretion to promote the intracellular shift of glucose and potassium, so therefore reducing the potassium.
Calcium wasn't administered as he was not showing signs, any clinical signs. He had a continuous ECG placed to monitor for any early stages of a cardiotoxicity due to this hyperkalemia. We gave him metoclopramide as a CRI IV.
We gave him ondansetron again, IV. He had Neopetin IV and we continued his paracetamol IV as well, all IV meds, just because he was, he was pretty flat. So we repeated an epoch again then at 11:30, so his calcium had come down a little bit further.
His potassium had increased slightly. His lactate bizarrely was then back within its normal limits, whether because this was we'd managed to, we'd hydrated him somewhat. But his urea and creatinine were higher still.
So the following morning, he had an epoch then performed again at 7 o'clock. His phosphate was flipped back. So it was, it had, had remained the same as it had, The following, sorry, his 7:30, his phosphate was the same as it had been the previous day.
They've done an epoch again at 4:00 a.m. And his calcium had snuck down again and continued to go down by again by 7:30 and his potassium was still continuously creeping up despite the glucose treatment and his lactate had again increased.
He was further He was, he was still esoteric, and he was still acidotic as well. So his ECG had remained unremarkable. This phosphate and potassium was still elevated.
And unfortunately, Charlie then went into a cardiopulmonary arrest. So we, CPR was initiated because What he, they had wanted resuscitation initially, but once we contacted them to say that Charlie had gone into cardiopulmonary arrest and that we were performing CPR, they instructed us to stop. So we did stop on our CPR.
So unfortunately, Charlie didn't make it through his crisis and, which is a very sad considering we'd seen him a couple of days before he again, he had a massive tumour burden and His chemotherapy had done its thing, had done its job, had worked very, very well, just worked too well for him and, and caused this syndrome for him. And unfortunately, once it kind of starts, it's usually very, very difficult to actually stop, any progression. And as I've shown, I've listed a bunch of papers, and you can see that dogs can survive this.
Unfortunately, it wasn't the case for dear Charlie. So this is just a little note on health and safety er when you are dealing with these patients that come in for a a tumour lysis event that this patient is cytotoxic, remember this patient has just had some chemotherapy so make sure that this patient is easily identifiable as cytotoxic within the in the hospital. Because there is still a risk of exposure to the clinical team of, cytotoxic residue, so this can be in the vomit, diarrhoea, saliva, and blood, and just to make sure that everyone is wearing proper PPE while they are handling him, and any waste from them, and that makes sure that they, disposing of any waste correctly as well.
So just a final recap for you guys to take away, so who is likely to be affected, these are cases with large tumour burden and haematological neoplasias such as lymphomas. Patients that are at an increased risk, so it's patients that have a weight loss prior to treatment, evidence of kidney disease already, patients treated with L asparaginase plus the presence of meta metabolic acidosis. It is likely to occur hours but possibly days after the administration of treatment, either chemotherapy or radiation, but it is usually within about 48 hours.
One of the talks I went to ACvim a couple of years ago. It was one of the texts that mentioned that it, it started within hours. I think by the time this dog had got home, they'd done the chemo, sent the dog on its way home, and by the time that dog got home, it was actually already starting to show signs, so it is just, completely, I'll say they use the word random as to when it's actually going to start.
So what happens is that they, there is rapid lysis of these malignant cells releasing all of the intracellular products into the systemic circulation. So lab and clinic clinical signs will be hyperphosphatemia, hyperkalemia, hypocalcemia, azotemia, metabolic acidosis. These guys are likely to be vomiting, lethargic, potentially bradycardic with that hyperkalemia, seizuring, showing some neurological signs.
And with the potential for an AKI and a reduced or. No, you're an output. So what we need to do is to correct any biochemistry, biochemical and electrolyte abnormalities, correction of metabolic acidosis and to restore restore perfusion as well.
So just again just to finish up, if you do need any oncology help contact us or your local friendly oncologist we are very happy to do advice calls or for referral as well. Just remember, remember to look after yourself and your team, especially dealing with oncology patients, sometimes I find, especially in a, for us in a referral setting as nurses and clinicians, we, I see our patients all the time. I get to know our patients and I get to know our owners very, very well.
I've been in oncology there now for 10 of the 19 years I've been at Northwestern. We get to really know these guys, so to lose a patient, the way that we, we can sometimes lose a patients like Charlie and the other case that I mentioned before, Strawberry. Charlie I've known for probably by this 0.3 months.
It, it's difficult, so we have to remember to look after ourselves and our team as well, especially when, we go through a, well, we go through a case like Charlie. I'd gone in on that morning to check on, check on him. And ended up kind of helping with his inpatient care because he was part of the inwards and he crashed while I was actually with him as well.
So I ended up part of the team that was performing CPR on him and it was incredibly difficult because he was a patient that I've known for for a while now and I got to know his owners. So yeah, we have to remember to look after ourselves. So I've listed all of the papers that I used for writing this presentation for you guys and they're all in the handouts as well and I've put lots of information in the handouts as well.
And then some more information as well if you want to read all things cancer. And if you do have any questions, please drop me a drop me an email, er there's my email address and the enquiries email for Northwest Veterinary Specialist. I'm happy to help as I can, er, but if you do want to discuss anything with any of the oncologists, please do give us a call, but I said I am very happy to answer any questions that you might have.
So thank you very much for listening to me talk about acute tumour lysis syndrome and hopefully it is something that you guys won't have to ever deal with in practise, but hopefully it just means you've got a few a little bit a bit of extra knowledge now to, Think about if you end up dealing with any oncology patients following treatment. Thank you.
