class: birds-title <div id="vantajs"></div> <div id="birds-writing"> <h1>Hyponatraemia</h1> <h3>SpR teaching | 30th Oct 2025</h3> </div> <script> VANTA.BIRDS({ //use this to comment out el: "#vantajs", backgroundColor: 0x7192f, backgroundAlpha: 0, color1: 0xff0000, color2: 0xd1ff, birdSize: 1.00, wingSpan: 12.00, speedLimit: 8.00, separation: 32.00, alignment: 10.00, cohesion: 10.00, quantity: 2.00 }); </script> ??? Other cases to consider including: - refractory hypoNa from Chyle leak - hypoNa from ileostomy - hypoNa from SiADH / reset osmostat --- # Assumed knowledge - hyponatraemia is (usually) a water problem - the difference between tonicity & osmolarity - the definition of effective & ineffective osmoles - why we check these tests in hyponatraemia: - P<sub>Osm</sub> - U<sub>Osm</sub> - U<sub>Na</sub> - indications for hypertonic saline - common causes of hyponatraemia - risk factors for osmotic demyelination --- # Basic concepts - hyponatraemia is a water problem - tonicity *vs.* osmolarity - effective *vs.* ineffective osmoles - interpreting lab data: - P<sub>Osm</sub> = is this hypotonic? - U<sub>Osm</sub> = is ADH acting appropriately / is solute intake limiting? - U<sub>Na</sub> = index of volume status - indications for hypertonic saline - common causes of hyponatraemia - risk factors for osmotic demyelination ---  ---  --- # Advanced concepts - not just a water problem (Edelman equation) - free water clearance / "Furst ratio" - use of ddAVP - therapy beyond fluid restriction: - solute supplementation - furosemide - vaptans - SGLT2i --- # Learning objectives Four cases of hyponatraemia to: - revise `basic concepts`: - hypertonic NaCl - RFs for ODS - introduce `advanced concepts`: - Edelman equation - Furst ratio - role for ddAVP - therapy for SiADH beyond fluid restriction .RWH_footnote_right[.RWH_footer_style[slides at: https://www.kidneyfish.net/talks/]] --- class: center, middle, inverse # .white[Case 1] --- # Case 1 **71M referred by GP with incidental hyponatraemia.** Routine bloods showed Na 124 (previously 132), Cr 127, eGFR 48 (>60). Patient was asymptomatic; said he drinks 4 pints of water plus tea every day. EtOH 24 units per week; non-smoker. <br> **PMHx:** HTN on candesartan 32 mg **o/e:** ABP 150/88; euvolaemic; blood +++ and protein +++ on dip Asked to drink less; candesartan halved; bloods repeated. --- # Case 1 <table style="width:75%; color: black; margin-left: auto; margin-right: auto;"> <thead> <tr> <th style="text-align:left;"> test </th> <th style="text-align:left;"> blood </th> <th style="text-align:left;"> urine </th> <th style="text-align:left;"> units </th> </tr> </thead> <tbody> <tr> <td style="text-align:left;width: 20em; "> Na </td> <td style="text-align:left;width: 10em; "> 132 </td> <td style="text-align:left;width: 10em; "> <20 </td> <td style="text-align:left;width: 10em; font-style: italic;"> mM </td> </tr> <tr> <td style="text-align:left;width: 20em; "> K </td> <td style="text-align:left;width: 10em; "> 4.7 </td> <td style="text-align:left;width: 10em; "> - </td> <td style="text-align:left;width: 10em; font-style: italic;"> mM </td> </tr> <tr> <td style="text-align:left;width: 20em; "> Cr </td> <td style="text-align:left;width: 10em; "> 168 </td> <td style="text-align:left;width: 10em; "> - </td> <td style="text-align:left;width: 10em; font-style: italic;"> mcM </td> </tr> <tr> <td style="text-align:left;width: 20em; "> Osm </td> <td style="text-align:left;width: 10em; "> 287 </td> <td style="text-align:left;width: 10em; "> 311 </td> <td style="text-align:left;width: 10em; font-style: italic;"> mOsm </td> </tr> </tbody> </table> <br> <br> <table style="width:75%; color: black; margin-left: auto; margin-right: auto;"> <thead> <tr> <th style="text-align:left;"> other results </th> </tr> </thead> <tbody> <tr> <td style="text-align:left;width: 50em; "> glucose 5.6 mM </td> </tr> <tr> <td style="text-align:left;width: 50em; "> FBC, TFTs, random cortisol, cholesterol, TRIGs all normal </td> </tr> <tr> <td style="text-align:left;width: 50em; "> gGT 341; other LFTs normal </td> </tr> <tr> <td style="text-align:left;width: 50em; "> IgG 18, IgA 13; no paraprotein </td> </tr> </tbody> </table> Bloods repeated again (x2) with similar results (Na 125 - 127 mM; plasma Osm 294 - 298); urea 6.6; Cr 143. ??? ### Further notes on case MCV was normal. Quizzed about EtOH - said 24 units per week. --- # Case 1 What would you advise the GP? .red[ - Who should advise on his hypoNa: renal or endocrine? - What could be causing the hyponatraemia? - What extra tests could help? - Is the hyponatraemia dangerous - i.e. is there a risk of cerebral oedema if it gets worse? - What management would you suggest? ] --- # Case 1 - learning points .red[What extra tests should we do?] -- <br> - paired lab (127) and gas (131) Na -- <br> `$$cOsm = 2 \times Na + urea + glucose$$` -- <br> `$$cOsm = 2 \times 127 + 7 + 6 = 267$$` -- <br> `$$OG = mOsm - cOsm = 294 - 267 = 27$$` -- <br> `$$EtOH = 87 g/dL \approx 87 /4 = 22$$` ??? ### Osmolar gaps - cOsm = 2*Na + urea + glucose = 276 vs. 287 (first bloods = gap 11) or 262 vs. 298 (second = gap 36) - cOsm = 266 vs. 294 (gap 28) or 266 + 87/3.8 = 266 + 23 = 289 (gap 5) - EtOH = 87 g/dL = 23 mOsm To convert mg/dL to mOsm for EtOH: divide by 3.8 (according to JM) - but this should be 4.6 - see below. Driving limit is 50 mg/dL. Normal OG < 10 mOsm. - paired lab (127) and gas (131) Na - lab EtOH level = 87 g/dL = 23 mOsm --- # Case 1 - learning points ### Causes of hypoNa with normal POsm i) pseudohyponatraemia = ISOtonic: <br>.orange[*hyperlipidaemia, paraproteinaemia, IVIg*] ii) additional effective osmole = HYPERtonic ('translocational'): <br>.orange[*glucose, mannitol, glycine*] iii) additional ineffective osmole = HYPOtonic: <br>.orange[*EtOH, urea, ethylene glycol*] <br> **i) and ii)** provide an explanation for the hypoNa; no risk of cerebral oedema **iii)** hypoNa not explained; risk of cerebral oedema ??? ### Clinical notes Pseudohyponatraemia caused because serum is diluted prior to analysis - so still seen with contemporary ISE methods (although was even worse in era of flame photometry). Can detect this by running a sample through ABG machine (as this uses an undiluted sample, so Na will be normal if pseudohypoNa) - see [European guidelines](https://pubmed.ncbi.nlm.nih.gov/24569125/). Glycine encountered in gynaecological / urological irrigation fluids - e.g. TURP syndrome. The risk of cerebral oedema is not elevated in i) and ii). The risk of cerebral oedema is high in iii) because serum tonicity is LOW - even when osmolality is high. <br> ### Basic concepts See [European guidelines](https://pubmed.ncbi.nlm.nih.gov/24569125/), [KI quiz](https://doi.org/10.1016/j.kint.2020.03.006) and [JAMA review](https://pubmed.ncbi.nlm.nih.gov/10030305/). Remember [basic definitions](https://derangedphysiology.com/main/cicm-primary-exam/required-reading/body-fluids-and-electrolytes/Chapter%20012/osmolarity-osmolality-tonicity-and-reflection-coefficient): - osmolality (or better "osmotic concentration") = number of solute particles per unit volume - tonicity = osmotic pressure between two compartments (a function of the effective osmoles - i.e. the osmolar concentration and the properties of the semi-permeable membrane) - reflection coefficient = a measure of how well a solute passes through a membrane (1 = impermeable; 0 = completely permeable) - effective osmole = unable to penetrate the membrane - ineffective osmole = able to freely cross the membrane Na, K etc. are effective osmoles. EtOH is an ineffective osmole (reflection coefficient for EtOH ~ 0). Urea is intermediate. Is hydrophobic and so doesn't cross lipid bilayers; reflection coefficient depends on expression of urea transporters. Reflection coefficient for urea ~ 0 for skeletal muscle and ~0.5 for the cerebral capillaries. Therefore rapid changes in urea can cause cerebral oedema (e.g. in dialysis equilibrium) - but for the purposes of evaluating hypoNa, can consider urea as an ineffective osmole (as will have equilibrated when not changing rapidly). See [Sterns](https://doi.org/10.1038/ki.2014.320) and [Halperin](https://pubmed.ncbi.nlm.nih.gov/8712203/) reviews. NB Urea is [an effective osmole in the distal nephron](https://doi.org/10.1159/000503773) - hence its utility in treating SiADH. --- # Case 1 - learning points `Clinical pearls:` - check a sample on gas machine to pick up pseudo-hypoNa - check EtOH levels (and divide by \~4 to convert mg/dL to mOsm) <br> `Causes of hypoNa in EtOH:` - hypovolaemia (50 %) - pseudohypoNa from hyperTRIGs (25 %) - beer potomania (10 %) - other (15 %) ??? At one point, was thought that the contribution of EtOH to Osm may be higher than its molar concentration - so conversion factors of 3.7 -- 4.0 used. However, this was based on flawed reasoning, so [it is in fact correct to convert based on its molar concentration](https://doi.org/10.3389/fmed.2019.00306) (i.e. divide by 4.6 as MW is 46 g/mol). In practice, easiest to remember by dividing by 4 to approximate. Figures from small [Greek case-series](https://pubmed.ncbi.nlm.nih.gov/11093969/). --- class: center, middle, inverse # .white[Case 2] --- # Case 2 `79F, two weeks post-op after CABG`: - Na 112 mM (from 135 mM four days ago) - confused for 2 - 3 days - **PMH**: MI, HTN - **Rx**: dalteparin, aspirin, amlodipine, paracetamol, ranitidine, co-amilofruse, sertraline - complaining of headache; cannot recall heart surgery - warm peripheries, no oedema, JVP + 4 --- # Case 2 How do you manage her initial treatment? .red[ - What initial therapy would you prescribe? - Would treatment with IV 0.9% NaCl likely to cause the serum sodium to rise or to fall further? - Is the risk of over-correction low / medium / high? ] --- # Case 2 - learning points .red[What if we give normal (0.9%) saline?] -- <br> `$$U_{Osm} = \frac{OL}{V}$$` -- <br> `$$V = \frac{OL}{U_{Osm} \text{ fixed?!}}$$` -- <br> `$$0.5 = \frac{300}{600}$$` ??? At this point we don't know what UOsm is! So let's assume 600 for sake of argument. Actually turned out to be 400 mOsmM - so V = 0.75. --- # Hypertonic saline For acute hypoNa with any symptoms or chronic hypoNa with moderate or severe symptoms (nausea, vomiting, confusion, headache, seizures, coma...) `Local practice:` - 300 ml 1.8% over 30 mins - safe to give peripherally (but unlicensed) - target increase of 5 mM -- <br> `European guidelines:` - 150 ml 3% over 20 mins (2 ml/kg in extremes of BW); repeat up to 3x - then 1 ml/kg/hr to target 1 mM rise per hr until symptoms stop - stop at 10 mM rise (or 130 mM - whichever is lower) .RWH_footnote_right[.RWH_footer_style[Verbalis (Am J Med, 2013); Spasovski (NDT, 2014)]] ??? [SALSA RCT](https://doi:10.1001/jamainternmed.2020.5519): suggests bolus infusions preferable to continous ones (more rapid initial control and less need for therapeutic re-lowering). --- # Case 2 - closure `79F, two weeks post-op after CABG`: - Na 112 mM (from 135 mM four days ago) - BM 8 - POsm 240 mOsm - UOsm 395 mOsm - UNa 72 mM - UK 47 mM - TFTs and 9 am cortisol normal ??? Furst ratio ~ 1: fluid restriction should cut it. ---  ??? Adapted from Spasovski et al. (NDT, 2014). Reasons why kidneys may be unable or unwilling to excrete free water: - no water delivery to kidney (low GFR) - impaired free water generation = thiazides (NB also PG effect on AQP2) - impaired free water generation = loops (NB but also impaired medullary gradient = protective) - water reabsorption on CDs = ADH = volume / nausea / stress / drugs / paraneoplastic --- class: center, middle, inverse # .white[Case 3] --- # Case 3 **62M presents to medicine after several days of non-stop vomiting**. No diarrhoea. Recent diagnosis of lymphoma; awaiting chemotherapy. Not on any medications. No EtOH use. **o/e:** looks volume deplete; HR 106; ABP 109/59 mmHg. <table style="width:75%; color: black; margin-left: auto; margin-right: auto;"> <thead> <tr> <th style="text-align:left;"> test </th> <th style="text-align:left;"> blood </th> <th style="text-align:left;"> urine </th> <th style="text-align:left;"> units </th> </tr> </thead> <tbody> <tr> <td style="text-align:left;width: 20em; "> Urea </td> <td style="text-align:left;width: 10em; "> 24.7 </td> <td style="text-align:left;width: 10em; "> - </td> <td style="text-align:left;width: 10em; font-style: italic;"> mM </td> </tr> <tr> <td style="text-align:left;width: 20em; "> Cr </td> <td style="text-align:left;width: 10em; "> 146 </td> <td style="text-align:left;width: 10em; "> - </td> <td style="text-align:left;width: 10em; font-style: italic;"> mcM </td> </tr> <tr> <td style="text-align:left;width: 20em; "> Na </td> <td style="text-align:left;width: 10em; "> 121 </td> <td style="text-align:left;width: 10em; "> 14 </td> <td style="text-align:left;width: 10em; font-style: italic;"> mM </td> </tr> <tr> <td style="text-align:left;width: 20em; "> K </td> <td style="text-align:left;width: 10em; "> 2.1 </td> <td style="text-align:left;width: 10em; "> 40 </td> <td style="text-align:left;width: 10em; font-style: italic;"> mM </td> </tr> <tr> <td style="text-align:left;width: 20em; "> HCO3 (TCO2) </td> <td style="text-align:left;width: 10em; "> 51 </td> <td style="text-align:left;width: 10em; "> - </td> <td style="text-align:left;width: 10em; font-style: italic;"> mM </td> </tr> <tr> <td style="text-align:left;width: 20em; "> Cl </td> <td style="text-align:left;width: 10em; "> 54 </td> <td style="text-align:left;width: 10em; "> <10 </td> <td style="text-align:left;width: 10em; font-style: italic;"> mM </td> </tr> <tr> <td style="text-align:left;width: 20em; "> Osm </td> <td style="text-align:left;width: 10em; "> 273 </td> <td style="text-align:left;width: 10em; "> 424 </td> <td style="text-align:left;width: 10em; font-style: italic;"> mOsm </td> </tr> </tbody> </table> --- # Case 3 How do you manage his initial treatment? .red[ - What initial therapy would you prescribe? - Is the risk of over-correction low / medium / high? - What monitoring would you suggest? - How will you prevent or treat over-correction? - What effect will K<sup>+</sup> replacement have on the hyponatraemia? ] --- # Case 3 - learning points .red[What is risk of ODS?] -- <br> <table style="width:100%; color: black; margin-left: auto; margin-right: auto;"> <thead> <tr> <th style="text-align:left;"> RFs for over-correction </th> <th style="text-align:left;"> RFs for ODS </th> </tr> </thead> <tbody> <tr> <td style="text-align:left;width: 25em; "> volume depletion </td> <td style="text-align:left;width: 25em; "> Na < 105 mM </td> </tr> <tr> <td style="text-align:left;width: 25em; "> water restriction in polydipsia </td> <td style="text-align:left;width: 25em; "> EtOH </td> </tr> <tr> <td style="text-align:left;width: 25em; "> GCs in adrenal insufficiency </td> <td style="text-align:left;width: 25em; "> malnutrition </td> </tr> <tr> <td style="text-align:left;width: 25em; "> vaptans </td> <td style="text-align:left;width: 25em; "> liver disease </td> </tr> <tr> <td style="text-align:left;width: 25em; "> </td> <td style="text-align:left;width: 25em; "> hypoK </td> </tr> <tr> <td style="text-align:left;width: 25em; "> </td> <td style="text-align:left;width: 25em; "> hypoPO4? </td> </tr> </tbody> </table> --- # Case 3 - learning points  .RWH_footnote_right[.RWH_footer_style[Dunn (JCI, 1973)]] ??? Male rats. --- # Case 3 - learning points .red[Options to prevent over-correction?] -- i) `ddAVP clamp`: continuous 3% NaCl IVI plus ddAVP every 6 - 8 hrs ii) `pro-active`: ddAVP before PNa starts to rise iii) `re-active`: ddAVP (+/- 5%G) in response to urine output (or early rises in PNa) iv) `rescue`: ddAVP (+/- 5%G) to re-lower PNa once you have over-shot <br> -- `One straightforward (re-active) approach:` - monitor urine output; threshold = 1 ml per kg per hr (maximum 100 ml per hr) - give ddAVP 2 - 4 mcg (IV / SC) +/- 6 ml/kg 5%G bolus - consider repeat at 12 - 24 hrs ??? ### ddAVP clamp Technique developed by [Richard Sterns](http://dx.doi.org/10.1053/j.ajkd.2012.11.032) group at Rochester (NY). They calculate dose of 3% NaCl required to induce 6 mM rise in PNa over 24 hrs using Adrogue & Madias formula. They then give this as continuous IVI along with ddAVP 1 - 2 mcg IV or SC every 6 - 8 hrs. End up delivering average 6 ml/kg 3% NaCl and 2 mcg ddAVP in first 24 hrs. Contraindicated in psychogenic polydipsia (risk of ongoing water ingestion plus ddAVP) and in massive fluid overload. ### Re-active and resuce ddAVP Case series from [Sterns group](https://journals.lww.com/cjasn/Fulltext/2008/03000/DDAVP_Is_Effective_in_Preventing_and_Reversing.10.aspx) and [Parisienne ITU](https://journals.lww.com/cjasn/Fulltext/2014/02000/Use_of_Desmopressin_Acetate_in_Severe_Hyponatremia.5.aspx) demonstrate safety and efficacy of reactive / rescue ddAVP strategy. Typically 1 - 2 mcg DDAVP IV; typically repeated at 24 hrs. Urine output falls from c. 400 - 1200 ml/hr to under 100 ml/hr. ### Which strategy is best? This was the topic of a small systematic review](https://pubmed.ncbi.nlm.nih.gov/26031887/), a [large observational study from Toronto](https://pubmed.ncbi.nlm.nih.gov/29061503/) and [NephJC discussion](http://www.nephjc.com/news/ddavpclamp). The bottom line is that there is no informative RCT and the observational data are all hard to extrapolate. I think quite a strong argument for keeping things as simple as possible and using a strategy that local practitioners are familiar with. In the observational series, ddAVP use was paradoxically associated with more patients having unsafe (rapid) rises in PNa - mainly driven by rises prior to ddAVP use in "rescue" therapy. It was also associated with longer hospital stay and lower mortality (3.9 vs. 9.4%). ### Urine output thresholds Patients with hypovolaemic hyponatraemia are at particular risk of "over-correction" - i.e. a rapid rise in PNa that might precipitate osmotic demyelination. This is because after the initial phases of volume resuscitation, the volume stimulus to ADH secretion is removed and there is then a profound osmotic stimulus suppressing ADH production. The first clinical sign that over-correction is imminent is a rise in urine output. But how much urine is too much urine? Using some complicated mathematics and reasonable assumptions, [Buchkremer et al.](https://pubmed.ncbi.nlm.nih.gov/30122547/) used the Edelman equation to derive an estimate for this. ### ddAVP doses ddAVP = desmopressin acetate. Typically 1 - 2 mcg IV (or SC) for this indication. For comparison, in vWD is 300 ng/kg (= 20 mcg for 67 kg adult). --- # Case 3 - learning points .red[What effect will K supplementation have on PNa?] -- <br> .pull-left[  ] .pull-right[ `$$P_{Na} \propto \frac{Na_{e} + K_{e}}{TBW}$$` ] .RWH_footnote_right[.RWH_footer_style[Edelman (JCI, 1958); Rose (Am J Med, 1986)]] --- # Derivation of Edelman `$$ECF_{Osm} \approx 2 \times P_{Na}$$` .RWH_footnote_right[.RWH_footer_style[Verbalis (Am J Med, 2013); Rose (Am J Med, 1986)]] -- <br> `$$ECF_{Osm} = ICF_{Osm} = \frac{\text{total body solutes}}{\text{total body water}} \approx \frac{(2 \times Na_{e}) + (2 \times K_{e})}{TBW}$$` -- <br> `$$ECF_{Osm} \approx \frac{2 \times (Na_{e} + K_{e})}{TBW} \approx 2 \times P_{Na}$$` -- <br> .red[ `$$P_{Na} \approx \frac{Na_{e} + K_{e}}{TBW}$$` ] --- class: center, middle, inverse # .white[Case 4] --- # Case 4 **77M with fluid-electrolyte problems after cancer chemotherapy.** Oncology team asking for advice with managing oedema and hypoNa. **Background:** neoadjuvant chemo for oesophageal cancer: capcitabine, epirubicin and cisplatin. PMHx: HTN, prostatic hyperplasia. **Current problems:** poor oral intake; low albumin; oedema. Hyponatraemia despite stopping his usual bendroflumethiazide / omeprazole. Current meds: ranitidine, tamsulosin. **o/e:** oedema to knees; fluid intake (and urine output) of 1.5 - 2.0L per day charted. --- # Case 4 <table style="width:75%; color: black; margin-left: auto; margin-right: auto;"> <thead> <tr> <th style="text-align:left;"> test </th> <th style="text-align:left;"> blood </th> <th style="text-align:left;"> urine </th> <th style="text-align:left;"> units </th> </tr> </thead> <tbody> <tr> <td style="text-align:left;width: 20em; "> Urea </td> <td style="text-align:left;width: 10em; "> 5.4 </td> <td style="text-align:left;width: 10em; "> - </td> <td style="text-align:left;width: 10em; font-style: italic;"> mM </td> </tr> <tr> <td style="text-align:left;width: 20em; "> Cr </td> <td style="text-align:left;width: 10em; "> 60 </td> <td style="text-align:left;width: 10em; "> - </td> <td style="text-align:left;width: 10em; font-style: italic;"> mcM </td> </tr> <tr> <td style="text-align:left;width: 20em; "> Alb </td> <td style="text-align:left;width: 10em; "> 18 </td> <td style="text-align:left;width: 10em; "> - </td> <td style="text-align:left;width: 10em; font-style: italic;"> g/L </td> </tr> <tr> <td style="text-align:left;width: 20em; "> Na </td> <td style="text-align:left;width: 10em; "> 127 </td> <td style="text-align:left;width: 10em; "> 78 </td> <td style="text-align:left;width: 10em; font-style: italic;"> mM </td> </tr> <tr> <td style="text-align:left;width: 20em; "> K </td> <td style="text-align:left;width: 10em; "> 3.7 </td> <td style="text-align:left;width: 10em; "> 60 </td> <td style="text-align:left;width: 10em; font-style: italic;"> mM </td> </tr> <tr> <td style="text-align:left;width: 20em; "> HCO3 (TCO2) </td> <td style="text-align:left;width: 10em; "> 26 </td> <td style="text-align:left;width: 10em; "> - </td> <td style="text-align:left;width: 10em; font-style: italic;"> mM </td> </tr> <tr> <td style="text-align:left;width: 20em; "> Mg </td> <td style="text-align:left;width: 10em; "> 0.63 </td> <td style="text-align:left;width: 10em; "> - </td> <td style="text-align:left;width: 10em; font-style: italic;"> mM </td> </tr> <tr> <td style="text-align:left;width: 20em; "> Osm </td> <td style="text-align:left;width: 10em; "> 252 </td> <td style="text-align:left;width: 10em; "> 322 </td> <td style="text-align:left;width: 10em; font-style: italic;"> mOsm </td> </tr> </tbody> </table> <br> <table style="width:75%; color: black; margin-left: auto; margin-right: auto;"> <thead> <tr> <th style="text-align:left;"> other results </th> </tr> </thead> <tbody> <tr> <td style="text-align:left;width: 50em; "> uACR 18 mg/mmol </td> </tr> <tr> <td style="text-align:left;width: 50em; "> FBC, TFTs, random cortisol all normal </td> </tr> </tbody> </table> --- # Case 4 What would you advise the oncology team? .red[ - What is the cause of his hyponatraemia? - Should we suggest furosemide? - How much of a fluid restriction would you suggest (e.g. in L per day)? - What other management would you suggest? ] --- # Case 4 - learning points .red[How much of a fluid restriction does he need and should we give furosemide?] `$$EFWC \approx{V}\times(1-\frac{U_{Na}+U_{K}}{P_{Na}})$$` -- `$$EFWC \approx{2}\times(1-\frac{78 + 60}{127}) = 2\times(1-1.1) = -0.2$$` -- `$$\text{urine:plasma electrolyte ratio, U:P(e)} = \frac{U_{Na}+U_{K}}{P_{Na}}$$` <table style="width:100%; color: black; margin-left: auto; margin-right: auto;"> <thead> <tr> <th style="text-align:left;"> U:P electrolytes </th> <th style="text-align:left;"> urine FWC </th> <th style="text-align:left;"> suggested daily fluid restriction </th> </tr> </thead> <tbody> <tr> <td style="text-align:left;width: 25em; "> UNa + UK > PNa </td> <td style="text-align:left;width: 25em; "> negative </td> <td style="text-align:left;width: 50em; "> 500 ml (+ furosemide + NaCl) </td> </tr> <tr> <td style="text-align:left;width: 25em; "> UNa + UK ~ PNa </td> <td style="text-align:left;width: 25em; "> zero </td> <td style="text-align:left;width: 50em; "> 500 - 800 ml </td> </tr> <tr> <td style="text-align:left;width: 25em; "> UNa + UK < PNa </td> <td style="text-align:left;width: 25em; "> positive </td> <td style="text-align:left;width: 50em; "> > 1000 ml </td> </tr> </tbody> </table> *(assumes: standard insensible FW losses, normal diet, Na/K losses replaced)* ??? Furst et. al (Am J Med Sci, 2000). Main assumptions (some acknowledged by Furst but better articulated by [Shah & Bhave, 2018](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5925609/)): - 300 ml metabolic free water generation - 600 ml water in food - 800 ml (500 ml per m2 = 10 ml per kg) insensible losses, of which 60% from skin and 40% from alveoli - 300 ml water loss in stool (but isotonic so no effect on EFWC) Overall, in most patients there is an insensible EFW balance of ~zero (as metabolic water plus food = 0.9L and insensible losses through skin and lung = 0.9L; sweat and stool are negligible). So urinary free water clearance matches intake. (Furst et al. seem to ignore water content of food, so presumably this would be included in their calculation of any fluid allowance - which is a bit confusing.) Revise insensible FW losses... - downward by 40% if on humidifed O2 - upwards if excessive sweating (sweat is hypotonic) - upwards if osmotic (but not secretory) diarrhoea... - ...NB osmotic diarrhoea due to CHO malabsorption (lactose intolerance), Mg, PO4, SO4 (e.g. laxatives / antacids)... - ...NB secretory diarrhoea due to bile acid malabsorption, non-osmotic laxatives, IBD, autonomic neuropathy... --- # Case 4 - learning points .red[What other management would you suggest?] <br> `$$EFWC \approx{V}\times(1-\frac{U_{Na}+U_{K}}{P_{Na}})$$` -- `$$EFWC \approx\frac{OL}{U_{Osm}}\times(1-\frac{U_{Na}+U_{K}}{P_{Na}})$$` -- <br> `Options for tricky hyponatraemia:` - furosemide - NaCl supplements - urea supplements (or better dietician / protein supplements) - SGLT2i? - almost never vaptans ??? Remember carbohydrates metabolised to CO<sub>2</sub> and H<sub>2</sub>O (no solute); proteins metabolised to urea (and CO<sub>2</sub> and H<sub>2</sub>O). --- class: center, middle, inverse # .white[Take-home messages] --- # Take-home learning points - causes of hypoNa without low POsm - check VBG and EtOH - `\(V = \frac{OL}{U_{Osm}}\)` ...so normal saline can exacerbate hypoNa - 1 ml per kg per hr (up to 100 ml/hr) as threshold for over-correction - ddAVP 1 - 2 mcg IV every 12 - 24 hrs - `\(P_{Na} \propto \frac{Na_{e} + K_{e}}{TBW}\)` ...so potassium supplementation will correct hypoNa - `\(\text{U:P(e)} = \frac{U_{Na}+U_{K}}{P_{Na}}\)` ...much easier than formal EFWC - loop diuretics likely to help if UOsm > 300 or UNa + UK > PNa (otherwise should exacerbate hypoNa) - `\(EFWC \approx\frac{OL}{U_{Osm}}\times(1-\frac{U_{Na}+U_{K}}{P_{Na}})\)` ...so solute supplementation can help --- 