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袈禧皇甫
5 years ago
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1 Journal Reading: 本檔僅供內部教學使用檔案內所使用之照片之版權仍屬於原期刊公開使用時, 須獲得原期刊之同意授權 presenter: R 陳俊愷

2 INTRODUCTION Recent large trials have shown that colloids may not be the best fluid choice for critically ill patients. disease severity and hemodynamic goals should be discuss Acute respiratory distress syndrome (ARDS) Recent research: endothelial dysfunction in ARDS, associated with sepsis. This review: discuss about the association of endothelial function and changes in endothelial cell structure in sepsis-induced ARDS. whether or not to use fluids presence/ absence of sepsis

3 Endothelial cells under normal conditions: a new model Since the study by Leathes and Starling on the absorption of fluids from the connective tissue spaces, filtration rate per unit area has been governed essentially by the following formula: P: hydrostatic pressure; π: oncotic pressures c: capillary lumen; t: tissue Jv/A: the filtration rate per unit area δ: the reflection coefficient to plasma proteins Lp: the conductivity of the vessel wall.

4 However, recent evidence has shown that the effective oncotic pressure is developed across the endothelial glycocalyx layer (EGL), minimizing the contribution of interstitial fluid oncotic pressure to filtration rate. Furthermore, most of the filtered fluid returns to the circulation as lymph The EGL is a matrix of glycoproteins and proteoglycans on the luminal side of endothelial cells degraded during inflammation by a tumor necrosis fator adependent mechanism and can be damaged during hyperglycemia. Therefore, EGL appears to be closely related to endothelial cell dysfunction.

6 Pulmonary endothelial cell damage in ARDS Damage to the alveolar-capillary membrane increased permeability and extravascular accumulation of protein-rich edema fluid. Vascular endothelial-cadherin is closely involved in the maintenance of endothelial cell integrity. Herwig et al. showed reduced expression of vascular endothelial-cadherin in lung specimens of patients with ARDS due to gram-negative sepsis. ARDS caused by septic insult.

7 An experimental study has shown that when vascular endothelial-cadherin is previously stabilized, for example by Slit protein through Robo4 receptor, endothelial integrity can be achieved even under conditions of ongoing inflammation. In other words, there is a general relaxation of cell cell and cell matrix forces, leading to high permeability.

8 So far, no clinical study evaluating the role of vascular endothelial-cadherin stabilization in endothelial permeability in ARDS patients. Several issues the influence of ARDS cause septic or nonseptic vascular endothelialadherin stabilization the role of type and volume of fluid administration in the endothelium

9 Epithelial cell injury in ARDS Epithelial cells injured owing to pneumonia, gastric broncho-aspiration and smoke inhalation Moriondo et al. showed an increase in glycosaminoglycan (GAG) extraction when mechanical ventilation and/or PEEP was associated with mild fluid load. ventilator-induced lung injury. Glycosaminoglycan (GAG) degradation/ remodeling not reflect an inflammatory process direct damaging impact attributable to the stress associated with positive pressure ventilation.

10 DIFFERENT FLUIDS Debate between fluids:

11 Fluids: pros and cons In order to restore a normovolemic status, the infusion of fluids is required. Regardless of the fluid choice, whether it is a crystalloid or colloid, the physiological electrolyte pattern of plasma should be mimicked as closely as possible. correct electrolyte imbalances and metabolic acidosis.

12 FLUIDS: PROS The following is a comparison between septic and non-septic patients.

13 Fluids in septic patients RBC are less deformable during severe sepsis and septic shock RBC diameter is four-fold higher than that of capillaries. Some studies have reported a decrease in blood viscosity secondary to improved erythrocyte deformability after colloid infusion improvement in microcirculatory flow In the 6S trial, the 6% HES 130/0.42 may lead to tissue storage and hemodilution due to overinfusion of starch molecules.

14 Fluids in septic patients The fluid status assessed by measuring CVP inaccurate and may lead to overinfusion. Acute kidney injury (AKI) defined as high levels of creatinine (>1.9 mg/dl) or urinary output < 500 ml/day. However, the creatinine levels decreased because of sepsis limitation as a reliable marker of AKI. increased Cr levels and oliguria during sepsis often occur after a window of opportunity for effective therapy.

15 Fluids in septic patients Evidence suggests that transfusion of RBCs is associated with higher mortality among patients in ICU. With respect to the Crystalloid versus Hydroxyethyl Starch Trial (CHEST) trial, there was an unmatched mortality of 17.5%, a rate relatively lower than the expected 26%. Low disease severity in the population. high chloride load was in the CHEST trial (154mmol/l), lead to AKI. Nevertheless, in the 6S trial, the authors used a balanced solution (127mmol/l in Ringer s acetate and 118 mmol/l in the HES solution) and detected a difference in 90-day mortality.

16 Fluids in septic patients In a prospective sequential comparison An increase in mean arterial pressure was observed in the HES group from the second to the 14th day, suggesting unnecessary fluid intake. The crystalloid group received higher amounts of norepinephrine than the colloid group on the fourth day until the eighth day. Crystalloid solutions led to instability? Whether the use of low volumes of colloid solutions may cause organ dysfunction (e.g. lung and kidney) and affect patient outcome?

17 Fluids in septic patients A randomized controlled trial conducted in the ICUs of 16 hospitals in Australia and New Zealand, albumin compared with saline showed that did not impair renal or other organ function may have decreased the risk of death Ongoing clinical trials (Volume Replacement with Albumin in Severe Sepsis) focusing on whether volume replacement with albumin (treated group) and its maintenance within the plasma physiological range (> 30 g/l) improves survival of patients with severe sepsis or septic shock. Preliminary data have shown that the use of albumin in the subgroup of patients with septic shock was associated with a reduction in mortality.

18 Fluids in nonseptic patients Patients who suffered major trauma, burns, head injuries and surgery benefit from fluid therapy. Non-septic scenario, endothelial adherens junctions are unlikely to be disturbed by inflammation, coagulation, fibrinolysis and regulation of vasomotor tone. Studies have shown that plasma expanders (dextran and HES) stabilize vascularized microfluidic scaffolds against endothelial delamination or denuding, enhancing vascular barrier function. Colloids [4% Gelofusine and 6% Voluven (HES 130/0.4)] were more effective blood volume expanders than a crystalloid No difference between the colloids.

19 Fluids in nonseptic patients At the end of the 1-h infusion, 68%, 21% and 16% of the infused volumes of 0.9% saline, Gelofusine and Voluven, respectively, had escaped from the intravascular to the extravascular space. In addition to intravascular resuscitation, single-center studies have reported similar results concerning the coagulation profile after infusion of HES 130/0.4 in trauma patients. A meta-analysis which pooled data from 17 studies showed that HES 130/0.40 was not associated with a greater risk of renal damage compared with control fluids tested in those studies in a general surgical population. The same result was noticed in a prospective trial in blunt and penetrating trauma patients.

20 Fluids in nonseptic patients A recent study analyzing randomized clinical trials regarding the use of tetrastarches during surgery showed kidney protection. In addition, 5% albumin solution and lactated Ringer s solution restored the hourly resuscitation ratio (I/O ratio) of fluid infusion to urine output.

21 FLUIDS: CONS The following is a comparison between septic and non-septic patients.

22 Fluids in septic patients Basel. Studies: 6% HES (130/0.4) V.S. crystalloids (0.9% NaCl) HES increases the risk of undergoing renal replacement therapy, RBC transfusion and severe adverse reactions in patients with sepsis. No difference in the primary endpoints, that is death from all causes at 90 days, It should be noted that the risk of death across subgroups was low, Expected a mortality around 26%, but the overall mortality in the trial was 17.5%, which, even with 7000 patients, raises the possibility that the study may be underpowered.

23 Fluids in septic patients The Scandinavian trial involved 798 patients with severe sepsis; among these, 1/3 had AKI. 6% HES (130/0.42) significantly increased the risk of death or dependence on dialysis at day 90, as compared with Ringer s acetate. Both groups of Scandinavian trial showed high mortality rates V.S. CHEST trial. Based on these results, the Surviving Sepsis Campaign was updated, and the previous recommendation for either natural/artificial colloids or crystalloids was modified to crystalloid infusion (minimum of 30 ml/kg for initial resuscitation), complemented by albumin infusion in cases of substantial crystalloids administration.

24 Fluids in nonseptic patients The CHEST trial, through a subgroup analysis in patients with Severe trauma The Fluids in Resuscitation of Severe Trauma trial showed an improvement in the biochemical markers of resuscitation in penetrating trauma patients who received 6% HES 130/0.4 The overall mortality was significantly higher in the HES group (21.4%) compared with the saline group (11.3%).

25 Fluids in nonseptic patients In retrospective survey and prospective studies patients subjected to 6% hetastarch in lactated electrolyte buffer (Hospira/HEXTEND ) had better outcomes. However, they received more blood and plasma transfusions than the standard of care group. Furthermore, the resulting hemodilution after colloid:crystalloid ratio greater than 1:2 may be associated with coagulopathy

28 Fluids in ARDS Early phase of ARDS Low peripheral perfusion Increased microvascular barrier permeability. Some amount of fluid should be administered V.S. exacerbate pulmonary edema Important clinical trials have shown that limited fluid intake in combination with diuretic treatment did not affect 60-day mortality, and increased oxygenation and the number of days without mechanical ventilation. Those patients were hemodynamically stable before randomization, which precludes its application in a situation often observed in the ICUs. Therefore, once hemodynamic stability is achieved, through an early intervention in order to restore peripheral demand, fluid intake should be decreased in order not to generate a positive fluid balance, which is clearly associated with poor outcomes.

29 The type of fluid in ARDS patients should be determined in order to maintain this stability. Studies showed that the addition of albumin to furosemide therapy in hypoproteinemic patients with acute lung injury/ards significantly improved oxygenation with greater net negative fluid balance and better maintenance of hemodynamic stability. The improvement in oxygenation was observed within 24 h up to 7 days. Sepsis represents a significant percentage (approximately 90%) of the total ARDS population. Fluid management should be conservative, after initial stabilization, and there is no evidence of superiority of colloidal molecules. Recent clinical trials: increased risk of renal dysfunction

30 However, when not combined, colloidal molecules may show beneficial results. In a nonsepsis preclinical model of hemorrhage, HES resuscitation compared favorably with crystalloid and gelatinbased fluid resuscitation in terms of variables reflecting pulmonary and renal injury. The fluid was assessed by measurement of intrathoracic blood volume index Also, that study showed no overinfusion of any fluids; however, even with similar thoracic volume, the amount of HES (837±82 ml) and gelatin (704±159ml) was lower than that of Ringer s acetate (2.250±764ml). Furthermore, on the basis of the aforementioned discussion, the differentiation between septic and nonseptic patients can be extrapolated to the ARDS population, as these patients respond differently to fluids because of not only direct or indirect etiology, but also the presence or absence of sepsis stimulus.

31 This is the main reason to discuss fluid therapy considering the presence or absence of sepsis. Endothelial injury could be more important in sepsis induced ARDS. Recent reviews have focused on a better understanding of the endothelium physiology and molecular biology aspects, thus proposing a new model of fluid filtration along the capillary. Within the therapeutic armamentarium against ARDS, fluids represent one more issue that future clinical trials need to consider, instead of analyzing the overall critically ill population

32 Conclusion There are few randomized clinical trials addressing fluid management in ARDS patients, and fluid therapy is therefore based on studies in critically ill patients. However, these patients respond differently to fluids depending on the presence or absence of sepsis. Colloid infusion: hemodilution, renal replacement therapy and coagulopathy Notwithstanding, the latest clinical trials deserve closer analysis, especially concerning the offer of an unrestricted amount of fluid allied to the use of unreliable hemodynamic parameters. Studies on the use of albumin in critically ill patients are underway, and retrospective analyses have shown beneficial results. Randomized clinical trials on fluid management should be performed in ARDS patients, taking into account the understanding of endothelium physiology.

33 Thanks for your attention!!

Microsoft PowerPoint - HES or saline pptx

Microsoft PowerPoint - HES or saline pptx HYDROXYETHYL STARCH OR SALINE FOR FLUID RESUSCITATION IN INTENSIVE CARE N Engl J Med. 2012 Nov 15;367(20):1901-11 本檔僅供內部教學使用檔案內所使用之照片之版權仍屬於原期刊公開使用時, 須獲得原期刊之同意授權 R 黃心治 Background 0.9% sodium chloride (saline)