Balanced Crystalloids Webinar February 2023[2207].pptx

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1. Balanced Crystalloids in clinical settings 1

2. Points to be discussed What is Balanced Crystalloid? A brief history Balanced Crystalloids Vs NS? Global Clinical Evidence: Balanced Crystalloid Clinical Guidelines Balanced Crystalloid: Unmet needs of Indian patients- A clinician’s opinion Clinician’s perspective (case studies) Closing remarks 2

3. BALANCED CRYSTALLOIDS A crystalloid solution with chemical composition as close as possible to that of plasma Produces a predictable and sustainable increase in intravascular volume without changing electrolytes concentration in plasma This is important for maintaining fluid and electrolyte balance during IV infusion in hospitalized patients So called “Normal” saline is neither “Normal” or “Balanced”! 50% higher chloride Vs Plasma No electrolytes except Na + and Cl - Leads to hyperchloremic metabolic acidosis in some patients 3

4. History: BALANCED CRYSTALLOIDS 4

5. History of IV fluid Infusion

6. Human Plasma Vs IV infusion Solutions Osmolality mOsm /kg Tonicity Na + Cl - K + Mg + Ca 2+ Buffer Plasma 288 Reference 140 103 4.5 2 2.5 4 2 0.9% NaCl 308 So Called Isotonic 154 154 Balanced Crystalloids 294 Isotonic 140 98 5.0 3 50 Balanced Crystalloids have more similar electrolytes and osmolarity with human plasma than so called “Normal Saline”.

7. SID (Strong I on Difference) & Buffering Capacity of IV fluids Weak anions are responsible for buffering capacity of IV fluids. Plasma proteins are major buffers in blood A buffer pair is a week acid, which enters equilibrium with its corresponding week base at the given pH Strong cations predominate in the plasma at physiologic pH leading to a net positive plasma charge of approximately +40 to 45. SID can be estimated as follows: SID = [strong cations] – [strong anions] = [Na + + K + + Ca 2+ + Mg 2+ ] – [Cl - + lactate - ]

8. Strong ion difference Lower SID: Acidosis- As Normal Saline has SID of 0, its infusion to plasma will reduce SID of plasma (which is around 40) and will lead to acidosis Balanced Crystalloids have SID of 50, similar to plasma. Infusion of Balanced Crystalloids will not lead to any major change in pH, No acidosis

9. Balanced Crystalloids Vs NS? 9

10. 52 serving packets One liter NS salt = salt in 53 serving of Lays chips

11. Limitations of So called “Normal” Saline

12. Global Clinical Evidence: Balanced Crystalloids 12

13. Conditions where Balanced Crystalloids are preferred NS: Normal Saline, RL: Ringer Lactate

14. 1. Balanced Crystalloids in Critically Ill Adults: A Systematic Review and Meta-analysis 13 studies (n = 30 950) were included. Balanced crystalloids demonstrated lower hospital or 28-/30-day mortality (risk ratio [RR] = 0.86; 95% CI = 0.75-0.99;  I 2  = 82%) in observational studies (RR = 0.64; 95% CI = 0.41-0.99;  I 2  = 63%) New acute kidney injury occurred less frequently with balanced crystalloids (RR = 0.91; 95% CI = 0.85-0.98;  I 2  = 0%), though progression to renal replacement therapy was similar (RR = 0.91; 95% CI = 0.79-1.04;  I 2  = 38%). Annals of Pharmacotherapy 2020, Vol. 54(1) 5–13 Conclusion and Relevance:   Resuscitation with balanced crystalloids demonstrated lower hospital or 28-/30-day mortality compared with saline in critically ill adults. Balanced crystalloids should be provided preferentially to saline in most critically ill adult patients .

15. I. Chloride rich Vs chloride restricted IV Fluid infusion and kidney injury in critically ill patients * a lactated solution (Hartmann solution), a balanced solution (Plasma- Lyte 148), and chloride-poor 20% albumin was used during intervention period JAMA.  2012;308(15):1566–1572. doi:10.1001/jama.2012.13356

16. I. Chloride rich Vs chloride restricted IV Fluid infusion and kidney injury in critically ill patients Comparing the control period with the intervention period: The mean serum creatinine level was increased in control period [22.6 µ mol /L (95% CI, 17.5-27.7 µ mol /L) vs 14.8 µ mol /L (95% CI, 9.8- 19.9 µ mol /L) (P=.03)] The incidence of AKI* was 14% (95% CI, 11%-16%; n=105) vs 8.4% (95% CI, 6.4%-10%; n=65) (P.001) The use of RRT was 10% (95% CI, 8.1%-12%; n=78) vs 6.3% (95% CI, 4.6%- 8.1%; n=49) (P=.005). *Incidence of AKI according to the risk, injury, failure, loss, end-stage (RIFLE) system definitions. Results: JAMA.  2012;308(15):1566–1572. doi:10.1001/jama.2012.13356

17. Incidence of Acute Kidney Injury Stratified by Risk, Injury, Failure, Loss, and End-Stage (RIFLE) Serum Creatinine Criteria The implementation of a chloride-restrictive strategy in a tertiary ICU was associated with a significant decrease in the incidence of AKI and use of RRT. I. Chloride rich Vs chloride restricted IV Fluid infusion and kidney injury in critically ill patients

18. 2. Balanced Crystalloids in Sepsis: SMART study Sub-analysis Total 1641 patients with sepsis admitted in Medical ICU were treated with either balanced crystalloids (n=824) or normal saline (n=817) Benefits observed with Balanced crystalloids Vs NS Lower 30 days in-hospital mortality Lower incidence of MAKE30 (major adverse kidney events) within 30 days aOR: adjusted odds ratio, CI: Confidence Interval, Am J Respir Crit Care Med 2019; 200(12): 1487–1495 MAKE30: D eath, new receipt of renal replacement therapy, or persistent renal dysfunction at the first of hospital discharge at 30 days Conclusions In ICU patients with sepsis, use of balanced crystalloids was associated with a lower 30-day in-hospital mortality and better renal outcomes Vs use of saline

19. 3. Balanced Crystalloids in DKA A recent (2022) meta-analysis compared use of Balanced crystalloids* and NS for DKA management Total 482 patients were included from 8 randomized controlled trials in the analysis. Use of Balanced crystalloids had following advantages over NS 1. Faster resolution of DKA by 3.51 hours (p=0.008) 2. Reduced hospital stay by 0.89 days (p=0.001) No difference in mortality between two groups, A trend toward lower serum chloride and higher serum bicarbonate in Balanced crystalloids group Diabetic Ketoacidosis (DKA) NS: Normal Saline, DKA: Diabetic Ketoacidosis, * including PlasmaLyte, Ringer’s lactate, Ringerfundin, and Hartmann’s solution Crit Care Explor 2022 Jan 6;4(1):e0613).

20. 4. Balanced Crystalloids in postoperative patients A. Liver Surgery A clinical study compared use of Balanced Crystalloids vs RL in 104 donors undergoing liver surgery (right hepatectomy) Benefits of Balanced Crystalloids Vs RL group. Lower lactate concentration (3.3 Vs 4.2 mmol/L, p=0.005) Lower Prothrombin time and total bilirubin (Liver function) Higher albumin levels Conclusion :  No n-lactated balanced crystalloids may have important advantages Vs RL, concerning lactate and liver function profiles, in living donors undergoing right hepatectomy. Acta Anaesthesiol Scand 2011 May;55(5):558-64

21. 4. Balanced Crystalloids in postoperative patients B. Open Laparotomy In a retrospective observational study, u se of Balanced Crystalloids in postoperative (open abdominal surgery) patients had following benefits over NS Lower rates of in-hospital mortality (2.9% Vs 5.6% P < 0.001) Lower risk of major complications (23% Vs 33.7% P < 0.001), Post-operative infection (P < 0.006), Blood transfusions (P < 0.001), Electrolyte disturbance (P < 0.046) and Acidosis investigation (P < 0.001) and intervention (P = 0.02) Ann Surg 2012; 255: 821-829)

22. 2019 ERAS/ESTS Guidelines: Lung Surgery Recommendation statement Evidence Level Recommendation grade For Perioperative fluid management, Balanced crystalloids are the intravenous fluid of choice and are preferred to 0.9% saline High Strong European Journal of Cardio-Thoracic Surgery 55 (2019) 91–115 ERAS: Enhanced Recovery After Surgery ESTS: European Society of Thoracic Surgeons 2019 guidelines for lung surgery by ESTS strongly recommend balanced crystalloids over normal saline for perioperative fluid management

23. 2021 Surviving Sepsis Campaign: Guidelines for Management of Sepsis and Septic Shock Recommendation statement Evidence Level Recommendation For adults with sepsis or septic shock, we suggest using balanced crystalloids instead of normal saline for resuscitation. low quality of evidence Weak Evans L et al. Critical Care Medicine 2021;49(11):e1063-e1143 This recommendation is based on the pre-specified subgroup analysis of SMART trial with patients admitted with sepsis in all participating ICUs, 30-day mortality was lower in those receiving balanced solutions, compared to normal saline (OR, 0.80; 95% CI, 0.67−0.94)

24. Balanced Crystalloid: Unmet needs of Indian patients- A clinician’s opinion there is no major emphasis on the chloride as electrolyte in day to day clinical practice. Hyperchloremic acidosis is not seen as iotrogenic Since the childhood NORMAL SALINE is considered as the synonimaus of the crystaloids no major challenge has posted against the supremacy of the title No trial’s so far has given outright advantages Always acidosis/alkalosis refered in reference to the hydrogen ions and bicarbonates Cost of the newer balanced saline were more than five times higher. 24

25. Case Studies Case no 1 a case of the acute appendicitis, perforation and septicaemia got operated for same Required fluid resuscitation , had acute renal failure recovered 25 Day 1 Fluid resuscitation {2 litre ns with in 10 hr} Serum sodium 134 Serum chloride 98 PH 7.23 Creat 1.4 Day 2 Fluid resuscitation {3.4 litre ns plus 1 litre in ot } Sodium 144 Chloride 107 PH 7.3 Creat 1.8 Day 3 Fluid resuscitation{ 2 litre in 24 hrs} Sodium 151 Chloride 117 PH 7.2 Creat 2.2

26. SID SID 40 30 26 K, MG CA NA 140 lactate Cl 104 K, MG CA NA 144 lactate Cl 114 Chloride rich resuscitation (0.9%)

27. Case study case no. 2 A case 50 yrs old female with diabetes ketosis,HBA1c 13 ,acetone 75 with severe respiratory distress admiited to hospital 27 On admission NA 136 K 5.5 CL 99 Creat 0.93 PH 6.9 Fluid 3lit/6hrs Crystaloids 0.9% After 12 hrs 146 3.4[replacement] 110 1.3 7.08 200ml/hrs 0.9% After 24 hrs 153 3.6 118 1.7 7.2 150ml/hr 0.45% After 48 hrs 153 3.7 118 2.0 7.18 100ml/hr Alternate 0.45% and dextrose 5%

28. Take Home Message