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Fluids In Sepsis-Evidence And Cost PowerPoint Presentation

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Description : Check out this medical PowerPoint presentation titled "Fluids in Sepsis - Evidence and Cost" by Albert Farrugia PhD and Megha Bansal M Econ.

This medical PowerPoint presentation talks about sepsis, a life-threatening condition that occurs when the bodys response to infection causes tissue damage and organ dysfunction. Fluid resuscitation is a key component of the management of sepsis, as it helps to maintain blood pressure, improve organ perfusion, and prevent organ failure.

There is a considerable body of evidence supporting the use of fluids in the management of sepsis. The Surviving Sepsis Campaign (SSC) guidelines recommend an initial fluid bolus of 30 mL/kg of crystalloid for patients with sepsis-induced hypotension or elevated lactate levels. Subsequent fluid management should be guided by frequent reassessment of clinical response, as well as monitoring of hemodynamic parameters such as blood pressure, heart rate, and urine output.

However, there is also evidence to suggest that excessive fluid resuscitation can be harmful in some patients with sepsis. A recent multicenter trial (the PROCESS trial) found that a conservative fluid management strategy, with a lower volume of fluids administered during the first 72 hours of sepsis management, was associated with a lower incidence of acute respiratory distress syndrome (ARDS) and improved survival, compared to a liberal fluid management strategy.

In terms of cost, fluid resuscitation is generally considered to be a relatively low-cost intervention. However, the cost of fluid management can vary depending on the type of fluid used, the volume administered, and the duration of treatment. In addition, there may be indirect costs associated with fluid management, such as increased length of hospital stay and the need for more intensive monitoring and support.

Overall, fluid resuscitation remains a key component of the management of sepsis, but the optimal volume and duration of fluid therapy may vary depending on the individual patients clinical response and underlying condition. Clinicians should carefully balance the potential benefits of fluid resuscitation against the risk of fluid overload and other potential adverse effects, and use evidence-based guidelines and protocols to guide their management decisions.

Tags : sepsis, infection causes tissue damage, organ dysfunction, Fluid resuscitation, critical care medicine, critical care medicine PowerPoint presentation

Published on : Mar 28, 2023 | Views : 601 | Downloads : 2

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Slide 1-

Fluids in SepsisEvidence and Cost Albert Farrugia PhD Megha Bansal M Econ Faculty of medicine, dentistry and health sciences The Seventh Annual Southeastern Critical Care Summit
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Disclosures I provide services to the pharmaceutical and biotechnology industry, including the manufacturers of therapies described in this presentation, who are also major sponsors of this Summit
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Current concepts of fluid exchange J Physiol 557.3 (3004) p704 Annu. Rev. Biomed. Eng. 2007. 9:121–67
Slide 4-

Shock Circulatory failure leading to inadequate perfusion and delivery of oxygen to vital organs Blood Pressure is often used as an indirect estimator of tissue perfusion Oxygen delivery is an interaction of Cardiac Output, Blood Volume, Systemic Vascular Resistance
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Shock States
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Severe Sepsis Major cause of morbidity and mortality worldwide. Leading cause of death in non-coronary ICU. 11th leading cause of death overall. More than 750,000 cases/Y of severe sepsis in US. In the US, > 500 patients die of severe sepsis daily. Consumes significant healthcare resources: Survivors of sepsis : ICU stay prolonged an additional 8 days. Additional costs incurred were $40,890/ patient. Estimated annual healthcare costs due to severe sepsis in U.S. exceed $16 billion.
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Definitions (ACCP/SCCM, 1991) Systemic Inflamatory Response Syndrome (SIRS): The systemic inflammatory response to a variety of severe clinical insults (For example, infection). Sepsis: The systemic inflammatory response to infection. Known or suspected infection, plus >2 SIRS Criteria. Severe Sepsis: Sepsis plus >1 organ dysfunction. MODS. Septic Shock. Sepsis induced with hypotension despite adequate resuscitation Perfusion abnormalities which may include, but are not limited to lactic acidosis, oliguria, or an acute alteration in mental status.
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Organ Ischemia in Sepsis Vasodilation leads to slow and sluggish organ perfusion pressure Some capillary beds perfuse normally Others are badly damaged and this leads to capillary leak, resulting in edematous tissues, tissue compression and prevention of oxygen exchange Due to venous stasis and activation of coagulation, small vessels become obstructed and blood flow stops
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Goals of Resuscitation Rivers Study- Early Goal Directed Therapy in Sepsis and Septic Shock Emergency department with severe sepsis or septic shock, randomized to goal directed protocol vs standard therapy prior to admission to ICU Early goal directed therapy conferred lower APACHE scores, indicating less severe organ dysfunction Rivers et al NEJM 2001
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Fluid Resuscitation of Shock Crystalloid Solutions “Normal” saline “Balanced” solutions Ringers Lactate solution Plasmalyte Colloid Solutions Hydroxyethyl Starch(es) Blood products (albumin, RBC, plasma)
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Choices and decision making in medical care Evidence RCTs Systematic reviews Cost effectiveness Total medical costs Role of Decision Analysis
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Which Fluids? An ideal resuscitative fluid would maintain intravascular volume without expanding the interstitial space. Crystalloid solutions are universally used for initial volume resuscitation in sepsis and septic shock…... Colloid solutions achieve hemodynamic goals more quickly than crystalloids with significantly less volume. As sepsis proceeds,…..significant tissue accumulation of resuscitation fluid occurs, and this may result in adverse effects.. Elsevier 2010
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Selected StatementsI Isotonic saline, when administered in large volumes, is associated with hyperchloremic acidosis; this may …be toxic.
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The Origins of 0.9% Saline Not a physiological fluid – based on a mistake by a physiologist called Hamburger in 1830s He thought concentration of salt in blood was 0.9% but it is nearer 0.6% 0.9% NaCl is not a maintenance fluid It has certain specific uses “One cannot fail to be impressed with the danger of the utter recklessness with which salt solution is frequently prescribed, particularly in the postoperative period…the disastrous role played by the salt solution is often lost in light of the serious conditions that call forth its use.” George H. Evans, JAMA 1911
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Gunnerson KJ, Saul M, He S, Kellum JA: Crit Care 2006, 10:R22 Hospital mortality associated with type of metabolic acidosis
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A & A October 2001 vol. 93 no. 4 811-816 Balanced Versus Saline-Based Solutions on Acid-Base and Electrolyte Status in Elderly Surgical Patients A & A October 2001 vol. 93 no. 4 811-816
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But……. The administration of buffered fluids to adult patients during surgery is equally safe and effective as the administration of non-buffered saline-based fluids. The use of buffered fluids is associated with less metabolic derangement, in particular hyperchloraemia and metabolic acidosis. Larger studies are needed to assess robust outcomes such as mortality.
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Fluids used : 2008 Cl- = 120 – 150 mmol/l 2009 Cl- = 19 – 109 mmol/l But……. Association of a chloride-restrictive (vs chloride-liberal) intravenous fluid strategy with AKI in critically ill patients JAMA. 308(15):1566-1572, October 17, 2012. DOI: 10.1001/jama.2012.13356
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Selected StatementsII Albumin is safe, although its cost-effectiveness has not been established, nor is there evidence of efficacy in sepsis.
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The role of albumin as a resuscitation fluid for patients with sepsis: A systematic review and meta-analysis Crit Care Med 2011 Vol. 39, No. 2, 386-91
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Albumin can ameliorate the disturbed microcirculatory effects of sepsis Albumin decreases neutrophil activation induced by fluid infusion, crystalloinds and synthetic colloids increase it. Rhee P, et al. Crit Care Med 2000; 28(1): 74-78. Albumin reduces TNF induced endothelial activation. Nohe et al Intensive Care Med 1999; 25: 1381-1385; Zhang et al Cardiovasc Res. 2002 Sep;55(4):820-9 Albumin solution reverses the LPS induced albumin leakage across vessel walls. Powers KA, et al. Crit Care Med 2003; 31: 2355-63 ;Anning PB et Intensive Care Med. 2004 Oct;30(10):1944-9 Albumin infusion results in sustained thiol levels in septic patients. Quinlan G, et al. Clin Sci 1998; 95: 459-65.
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Microcirculatory perfusion in sepsisPotentially impairing factors Spronk et al Critical Care 2004, 8:462-468
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Fluid Therapy in Septic Patients Ernest et al Critical Care Medicine:Volume 27(1)January 1999 pp 46-50 Albumin is retained intravascularly… …and expands plasma volume SAFE investigators Int Care Med 2011, 37 (1), 86-96
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RCTs - Albumin versus saline Sepsis and Septic Shock
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The power and the glory Theoretical Effect of a Drug for Septic Shock on All-Cause Mortality at 28 Days, According to Revised Estimates of Residual Attributable Mortality. Wenzel RP, Edmond MB N Engl J Med. 2012 May 31; 366(22):2122-4
Slide 26-

Albumin vs saline Sepsis and Septic ShockMortality All 0.83 p=0.011
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Systematic review of resuscitation of children with severe infection and shock Akech et al BMJ. 2010; 341: c4416 ] Trials of albumin in malaria
Slide 28-

N Engl J Med. 2011 Jun 30;364(26):2483-95 Mortality after fluid bolus in African children with severe infection - The FEAST Trial
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Selected StatementsIII HES formulations are widely used for fluid resuscitation in sepsis. Older, high molecular weight compounds should be avoided because of problems with coagulation and accumulation, particularly with renal failure.
Slide 30-

HES in sepsis – MA and RCTs
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HES and renal probleamsEarly MAs “Studies including sepsis patients revealed that HES treated individuals had a 55% increased risk of developing kidney failure and a 59% increased risk of requiring dialysis.” “There is insufficient clinical evidence to suggest that 6%130/0.4’s favourable pharmacokinetics compared to older HES products result in improved kidney outcomes.” Dart et al Cochrane Reports 2009 “The use of HES for acute volume resuscitation of critically ill patients, and in particular those with severe sepsis and septic shock, appeared to be associated with increased use of renal replacement therapy. “ “We do not recommend the routine use of starches for acute volume resuscitation in critically ill patients, particularly patients with severe sepsis or septic shock.” Zarychanski et al Open Medicine 2009
Slide 32-

Mortality following HES resuscitation Zarychanski et al Open Medicine 2009;3(4):e196–209
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Renal outcomes (RRT) following HES resuscitation Zarychanski et al Open Medicine 2009;3(4):e196–209
Slide 34-

Crystalloids Morbidity Associated with severe Sepsis CRYSTMAS study Adult patients with severe sepsis Crit Care. 2012 May 24;16(3):R94.
Slide 35-

Following the CRYSTMAS study (Crit Care. 2012 May 24;16(3):R94.) Approved Product Information for VoluvenTime to Renal Replacement Therapy “The number of subjects undergoing RRT was 21 vs 11 for the 90 day observation period and 17 vs 8 for the first 7 days of treatment. Mean Duration of RRT was 9.1 days in the Voluven arm vs 4.3 days in the saline arm. Kaplan-Meir curves for time to RRT showed a trend against Voluven.” Voluven PI included by FDA
Slide 36-

“6S” study N Engl J Med. 2012 Jul 12;367(2):124-34.
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“6S” study N Engl J Med. 2012 Jul 12;367(2):124-34. “….patients with severe sepsis who received fluid resuscitation with HES 130/0.4, as compared with those who received Ringer’s acetate, had a higher risk of death at 90 days, were more likely to receive renal-replacement therapy, and had fewer days alive without renal-replacement therapy and fewer days alive out of the hospital.”
Slide 38-

CHEST STUDY N Engl J Med. 2012 Nov 15;367(20):1901-11.
Slide 39-

CHEST STUDY N Engl J Med. 2012 Nov 15;367(20):1901-11. “…does not provide evidence that resuscitation with 6% HES (130/0.4), as compared with saline, in the ICU provides any clinical benefit to the patient. Indeed, the use of HES resulted in an increased rate of renal replacement therapy. Thus, the selection of resuscitation fluid in critically ill patients requires careful consideration of its safety, its potential effect on patient-centered outcomes, and its cost.”
Slide 40-

The FIRST trial - Distribution of renal outcomes in blunt and penetrating trauma by fluid group Br. J. Anaesth. (2011) 107 (5): 693-702.
Slide 41-

Hot off the press Three new meta analyses published on HES in the week beginning 18 February 2013 Intensive Care Med. 2013 Feb 14. [Epub ahead of print], Gattas DJ, Dan A, Myburgh J, Billot L, Lo S, Finfer S; CHEST Management Committee. BMJ. 2013 Feb 15;346:f839. doi: 10.1136/bmj.f839. Haase N, Perner A, Hennings LI, Siegemund M, Lauridsen B, Wetterslev M, Wetterslev J. JAMA. 2013 Feb 20;309(7):678-88. doi: 10.1001/jama.2013.430. Zarychanski R, Abou-Setta AM, Turgeon AF, Houston BL, McIntyre L, Marshall JC, Fergusson DA. All HES products increase mortality and the need for RRT Previous favorable risk/efficacy profile totally dependent on Boldt studies (retracted) “
Slide 42-

JAMA Editorial February 20, 2013 “….the harms of hydroxyethyl starch most likely outweigh the benefits and suggest that these products should not be used for acute volume resuscitation of critically ill patients.”
Slide 43-

Evidence from head to head comparison trials is often limited or unavailable Using evidence from A vs B and A vs C trials to draw conclusions about the effect of B relative to C It allows all evidence to be combined in a single analysis Inference based on more evidence can (usually) provide more precision Treatments can be ranked Better informed decisions 43 Indirect comparisons Networkmeta-analysis / mixed treatment comparisons Treatment A (crystalloid) Treatment B (albumin) Treatment C (HES) 43
Slide 44-

Network MA for studies in sepsisSearch strategy 6 5 1 1 Bansal et al 2013
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Network MA for studies in sepsisRanking probabilities of competing fluid treatments Bansal et al 2013
Slide 46-

No Money…… “Dear Chief Secretary, I'm afraid to tell you there's no money left” Outgoing Labour Chief Secretary to the UK Treasury Liam Byrne note to his successor in the incoming Coalition government 2010
Slide 47-

Decision tree to assess cost-effectiveness Fluids in sepsis
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Results of cost-effectiveness analysis * Years saved/lost compared to crystalloid.
Slide 49-

Summary/Conclusions Sepsis results in lowered tissue perfusion and can manifest shock requiring volume replenishment A variety of fluids for the treatment of sepsis have been proposed Evidence continues to accrue that colloids are required after initial crystalloid infusion Physiological indications that balanced crystalloids are preferable have not been confirmed in clinical trials in patients Albumin has been shown to improve outcomes in septic patients HES has been shown to increase mortality an cause renal damage Employing network meta-analysis and decision modeling allows direct comparison between fluid therapies In decision-making, a focus on total, long term costs needs to supersede short term considerations of individual interventions
Slide 50-

“and you pays your money, and you makes your choice” Mark Twain in Huckleberry Finn Money again
Slide 51-

“….choose wisely, for while the true Grail will bring you life, the false Grail will take it from you” The Knight in Indian Jones and the Last Crusade Choosing Fluids