Draft

195  Locke On Salt PGR

195.1 Summary

  • Episode 2: The Salt Strikes Back
  • On Diuresis
  • Review: Natriuresis based decongestion
  • The future is now?
  • A case, familiar to all:
  • A Case, continued
  • Bad ARDS Circle of Life
  • Goal: Explore H2O Balance vs Sodium Balance
  • Molar mass of sodium: 22.99 g/mol 22.99 g/mEq
  • Does someone who eats 2g of Na/d drink the same H2O as someone who eats 4g of Na/d?
  • Physiology Review
  • The nephron doesn’t have a dedicated method to excrete sodium.

195.2 Slide outline

195.2.1 Slide 1

  • Episode 2: The Salt Strikes Back
  • Brian Locke, MD
  • PGR 5/27/21 ### Slide 2
  • On Diuresis
  • PGR 3/4/21
  • Brian Locke, MD
  • Review from last time
  • Net fluid change and Net Sodium change don’t always go in the same direction
  • Na Balance, rather than fluid balance, is the most important metric of decongestion.
  • Fluid restrictions are not generally helpful in decongesting patients
  • ‘We’ (inpatient providers) frequently dose Lasix too low, wait too long to increase the dose, and stop diuresing too soon. ### Slide 3
  • Review: Natriuresis based decongestion
  • Simple: Spot urine Na > 100 2h after dose was probably effective (will lead to net 2g+ natriuresis in BID dosing)
  • Complex: ### Slide 4
  • The future is now? ### Slide 5
  • A case, familiar to all:
  • 68M with DM who is admitted to the ICU after a diagnosis of COVID.
  • His DM is mild (A1c 6.5%), with no nephropathy
  • He is admitted to the ICU after intubation for respiratory failure.
  • His initial ventilator oxygenation settings: 50% fiO2 and 12 cmh2o of PEEP but he subsequently worsens to 70% / 14.
  • Neuromuscular blockade and proning are initiated.
  • He is receives a 5d course of CTX/azithro. He is euvolemic on admission ### Slide 6
  • A Case, continued
  • He is difficult to sedate, and thus requires high dose propofol. He develops hyperTG. Switched to lorazepam 2mg q4, Fent 150 mcg/hr and ketamine at 0.4 mg/kg/hr to allow neuromuscular blockade. He is started on a cisatricurium drip 3-4 mcg/kg/min, which he is continued on for 18h per day.
  • Over the next 3 days, he develops a positive fluid balance. He also worsens to requiring 100% fio2 and 20 PEEP when supine.
  • I/O: Day 1 proning: 1L positive (mostly NS), Day 2 proning 1L positive (mostly NS), Day 3: 3L positive (enteral free water added) ### Slide 7
  • Bad ARDS Circle of Life
  • Many Drips
  • (in NS)
  • Lasix & no
  • free H2O
  • Fluid Overload
  • Hypernatremia ### Slide 8
  • Goal: Explore H2O Balance vs Sodium Balance
  • Review renal physiology that explains why sodium loading might be problematic
  • Review data regarding sodium loading and “fluid creep” in the ICU
  • Discuss clinical implications and strategies to avoid excess sodium
  • Water
  • Salt ### Slide 9
  • Molar mass of sodium: 22.99 g/mol 22.99 g/mEq
  • Na load in a normal diet (recommended 2.3g 100 mmol; actual 3.4g 148 mmol)
  • Average total osmolar load 10 mOsm/kg/day > 898 osm (men) and 774 osm (women)
  • Total water intake 3.46L (men) and 2.75L (women): 3.1L average – roughly 30% from water, 70% from soft drinks and food.
  • Average [Na] and [osm] of intake: 47 mEq/L of Na, 270 mOsm ### Slide 10
  • Does someone who eats 2g of Na/d drink the same H2O as someone who eats 4g of Na/d?
  • Yes – at steady state – in out.
  • Over a large range of sodium intake, urine production and thus fluid intake will be constant
  • More natriuresis occurs in people who eat more salt. ### Slide 11
  • Physiology Review
  • Large bolus of free water?
  • ADH shuts off. Kidneys produce dilute urine. Electrolytes and volume status unchanged.
  • For avg (10 mOsm/kg/day) diet, ADH fully off 50 mmol/L (maximally dilute) 70 kg person > 700 mmol load > 50 mmol/L excretion > 14L of free water can be excreted per day without perturbing sodium balance.
  • Large bolus of sodium?
  • Maximal natriuresis ~280 mmol/L (2x serum, roughly).
  • Why? There is NO active sodium excretion along the nephron ### Slide 12
  • The nephron doesn’t have a dedicated method to excrete sodium.
  • Instead, the kidneys concentrate urine by increasing urea concentration in the medulla.
  • Counter-intuitively, to maintain osmolality the major mechanism after an ingestion of salt is not thirst, but free water re-absorption in the kidney (ie. concentration of urine)
  • It takes time to generate this gradient
  • Kidneys retain water (with ADH) to maintain [Na] in serum in the interim
  • Glucocorticoid driven catabolism to generate urea
  • Increase urea in the renal medullary interstitium
  • Increase osmotic gradient to reabsorb free water ### Slide 13
  • If someone who normally eats low Na diet eats high Na diet, do they drink more water?
  • Healthy people randomized to either low sodium (0.5 g) to regular (3.2g) diet, then swap
  • After increased Na load: takes ~3-5 days to reach a new steady state with kidney able to match Na load
  • On the first day: only half of excess Na load excreted
  • The positive sodium balance caused fluid retention andan increase in body weight of over 1 kg.
  • No difference in fluid intake (free-water reabsorption makes up difference) ### Slide 14
  • Na and fluid load in this patient
  • 1L of NaCl 3.5gm (154 mmol Na) ~7 gm NaCl
  • Our case:
  • ~750 cc/d NS from Ketamine, 350 cc/d from Fentanyl 100 cc/d ciastricurium, 200 from CTX
  • ~4g of sodium just from sedation and NMB ### Slide 15
  • ADH is also a weak Anti-natriuretic Hormone
  • Healthy volunteers drank either:
  • Low hydration: free water 0.25 mL/kg q30m (35 mL/hr for 70kg) or
  • High hydration: water 2.0 mL/kg q30m ( 288 mL/h for 70kg).
  • Then received 250cc 2% NaCl
  • High hydration: excrete the extra sodium immediately.
  • Low hydration cannot (ADH crosstalk, maximal concentration ability of kidneys)
  • Meaning: the kidneys CANNOT create low free water, high Na urine ### Slide 16
  • Physiology in Health Volunteers vs ICU:
  • Patient characteristics:
  • Impaired handling of Na in low GFR states, the elderly
  • Disease characteristics
  • ATN (less concentration ability)
  • catabolism (need to excrete solutes)
  • hyperglycemia (osmotic diuresis) ### Slide 17
  • Physiology Review:
  • The kidneys have mechanisms to quickly adjust free water clearance.
  • The kidney does not have a fast mechanism to increase natriuresis – it takes several days and catabolism to achieve this.
  • Limitation in free water hampers natriuresis due to ADH crosstalk.
  • While the kidney is adapting to a new baseline sodium intake, fluid retention occurs.
  • Therefore, it is very hard to achieve balanced I/O during salt loading ### Slide 18
  • Na loading in the ICU
  • Fluid creep: fluids administered as vehicle for medication, TKO
  • Antwerp hospital Belgium 2007-2016, mixed ICU (45 bed)
  • 14650 patients, 103098 patient days ### Slide 19
  • Single-day, point prevalence survey: 46 Australian and New Zealand ICUs on 21 September 2011
  • Median sodium admin: 224.5 mmol (IQR, 144.9-367.6 mmol). 2.8 mmol/kg (IQR, 1.6-4.7 mmol/kg).
  • Patients Day 2-10 of ICU admission:
  • maintenance or replacement intravenous (IV) infusions, 69.3mmol; 30.9% of all sodium sources;
  • IV fluid boluses, 36.5 mmol; 16.3%;
  • IV drug boluses, 27.6 mmol; 12.3%;
  • enteral nutrition, 26.5 mmol; 11.8%;
  • IV drug infusions, 19.3 mmol; 8.6%;
  • IV flushes, 16.6mmol; 7.4%;
  • blood products, 13.5 mmol; 6%;
  • IV antimicrobials, 11.2mmol; 5%;
  • parenteral nutrition, 4.3 mmol; 1.9%.
  • Median 5 grams of Na per day
  • Double the usual intake ### Slide 20
  • TODO: No text extracted from this slide. ### Slide 21
  • What is the composition of insensible losses?
  • Estimated: 600—900 mL per day
  • Respiration: [Na] 0
  • Perspiration: [Na] 40.1 mEq per L
  • Stool? 250 mL per day, but huge variation in composition and volume of losses depending on pathology. ### Slide 22
  • Clinical impact
  • Malbrain 2014 meta-analysis: “A restrictive fluid management was associated with a lower mortality compared to patients treated with a more liberal fluid management strategy (24.7% vs 33.2%; OR, 0.42; 95% CI 0.32-0.55; P < 0.0001)” ### Slide 23
  • To be considered for additional fluids, you generally are not improving
  • The group who receives large volumes of fluid has been doing bad enough (despite other interventions) at each time point when fluids are considered and is thus not comparable to the group that did not receive fluids (who could either be doing badly and not received fluids – the intended comparator – or have responded to other treatment
  • Analogous to immortal time bias: patients who are responding to current therapy are generally not considered for additional fluid boluses. ### Slide 24
  • Clinical impact - FACTT / FACTT Lite
  • RCT comparison of fluid management strategy to target CVP 10-14 (liberal) vs CVP < 4 (conservative) in ARDS
  • Improved oxygenation, decreased days on ventilator, decreased time in ICU
  • Takeaway: avoiding congestion is important in these patients ### Slide 25
  • Clinical impact - TOPMAST trial
  • Blind randomization of 70 patients undergoing major thoracic surgery to [Na] 154 mmol/L vs [Na] 54 mmol/L fluid
  • Primary: Net fluid balance: Na154 +4.5L vs Na54 3.12L despite identical fluid infused
  • Secondary:
  • Pulmonary Edema: Na154 17%, Na54 3%
  • Electrolyte abnormalities:
  • Na154 – n3 had Na above 145.
  • N24 had Cl- above ULN
  • Na54 – n4 patients had Na
  • below 135. ### Slide 26
  • Prospective, observational study of N50 ventilated patients
  • Tracked net fluid (mean +2.6L) and net sodium balance (mean 717 mmol)
  • Positive cumulative sodium balance: correlated ro -0.36, p0.0001 with worsening next sodium P:F
  • Positive fluid balance: no correlation ro 0.1, p0.23 with worsening next day P:F ### Slide 27
  • What to do to avoid this? Na Stewardship
  • Don’t use maintenance fluids (duh).
  • Avoid sodium in fluid creep
  • Keep track of Na in
  • Maybe someday we’ll track Na output?
  • Give some free water
  • Diurese (Natriurese) your patients? (Maybe add a thiazide) ### Slide 28
  • Why do we dissolve medications in NaCl?
  • ICUs have pre-mixed versions of medications to deliver quickly (ie. antibiotics, fentanyl)
  • Some meds are sodium salts ( any negative ion paired with a sodium cation) – generally more soluble in water than the acid form
  • A few medications must be given in NS
  • It’s the default ### Slide 29
  • TODO: No text extracted from this slide. ### Slide 30
  • Before-after Australian ICU: D5W as default ### Slide 31
  • Can’t we just add furosemide ### Slide 32
  • Is this a problem? ### Slide 33
  • Case Resolution
  • Diuresed, got hypernatremic, slowly improved over the following week with decreased Na inputs. Extubated this morning. Developed pseudomonas VAP and remains intubated. ### Slide 34
  • Summary Points
  • Ease up on free water, clamp down on Na load
  • I/Os (any mL in is equivalent to any other mL in) mislead us – because the kidneys are very good at handling changes in free water intake, not good at handling boluses of sodium
  • Using D5w instead of NaCl should probably be our default on patients who have large medication intakes (e.g. on cis, fentanyl, ketamine, antibiotics) ### Slide 35
  • Bad ARDS Circle of Life
  • Many Drips
  • (in NS)
  • Lasix & no
  • free H2O
  • Fluid Overload
  • Hypernatremia
  • Use D5W instead
  • Driven By Na Overload
  • Liberal free water can allow natriuresis ### Slide 36
  • Take this all with… a grain of salt:
  • Van Regenmortel, N., Moers, L., Langer, T., Roelant, E., De Weerdt, T., Caironi, P., Malbrain, M.L., Elbers, P., Van den Wyngaert, T. and Jorens, P.G., 2021. Fluid-induced harm in the hospital: look beyond volume and start considering sodium. From physiology towards recommendations for daily practice in hospitalized adults. Annals of Intensive Care, 11(1), pp.1-12.
  • Bankir L, Perucca J, Norsk P, Bouby N, Damgaard M. Relationship between sodium intake and water intake: the false and the true. Ann Nutr Metab. 2017;70(Suppl 1):51–61.
  • Van Regenmortel N, Verbrugghe W, Roelant E, Van den Wyngaert T, Jorens PG. Maintenance fluid therapy and fluid creep impose more significant fluid, sodium, and chloride burdens than resuscitation fluids in critically ill patients: a retrospective study in a tertiary mixed ICU population. Intensive Care Med. 2018;44(4):409–17
  • George Institute for Global H, Bihari S, Peake SL, Seppelt I, Williams P, Bersten A, et al. Sodium administration in critically ill patients in Australia and New Zealand: a multicentre point prevalence study. Crit Care Resusc. 2013;15(4):294–300.
  • Van Regenmortel, N., Hendrickx, S., Roelant, E., Baar, I., Dams, K., Van Vlimmeren, K., Embrecht, B., Wittock, A., Hendriks, J.M., Lauwers, P. and Van Schil, P.E., 2019. 154 compared to 54 mmol per liter of sodium in intravenous maintenance fluid therapy for adult patients undergoing major thoracic surgery (TOPMAST): a single-center randomized controlled double-blind trial. Intensive care medicine, 45(10), pp.1422-1432.
  • Bihari S, Peake SL, Prakash S, Saxena M, Campbell V, Bersten A. Sodium balance, not fluid balance, is associated with respiratory dysfunction in mechanically ventilated patients: a prospective, multicentre study. Crit Care Resusc. 2015;17(1):23–8.
  • Lansink-Hartgring, A.O., Hessels, L., Weigel, J., de Smet, A.M.G., Gommers, D., Panday, P.V.N., Hoorn, E.J. and Nijsten, M.W., 2016. Long-term changes in dysnatremia incidence in the ICU: a shift from hyponatremia to hypernatremia. Annals of intensive care, 6(1), pp.1-8.
  • Bihari, S., Prakash, S., Potts, S., Matheson, E. and Bersten, A.D., 2018. Addressing the inadvertent sodium and chloride burden in critically ill patients: a prospective before-and-after study in a tertiary mixed intensive care unit population. Critical Care and Resuscitation, 20(4), p.285.

195.3 Learning objectives

  • Episode 2: The Salt Strikes Back
  • On Diuresis
  • Review: Natriuresis based decongestion
  • The future is now?
  • A case, familiar to all:

195.4 Bottom line / summary

  • Episode 2: The Salt Strikes Back
  • On Diuresis
  • Review: Natriuresis based decongestion
  • The future is now?
  • A case, familiar to all:

195.5 Approach

  1. TODO: Outline the initial assessment or decision point.
  2. TODO: Outline the next diagnostic or management step.
  3. TODO: Outline follow-up or escalation criteria.

195.6 Red flags / when to escalate

  • TODO: List red flags that require urgent escalation.

195.7 Common pitfalls

  • TODO: Capture common errors or missed steps.

195.8 References

TODO: Add landmark references or guideline citations.

195.9 Slides and assets

195.10 Source materials