This document discusses fluid therapy in emergency care, covering topics such as: - Types of fluids used for resuscitation including crystalloids, colloids, blood, and hypertonic saline. - Factors to consider in fluid resuscitation for hemorrhagic shock such as volume, blood oxygen carrying capacity, and coagulation status. - Debate around delayed versus immediate fluid resuscitation for penetrating trauma, with some evidence that delayed resuscitation may improve outcomes. - Uncertainties remain regarding best practices for fluid resuscitation depending on trauma type and patient characteristics.

1. Fluid Therapy in Emergency Care Dr. Rashidi Ahmad Medical Lecturer/emergentist School Of Medical Sciences USM Health Campus Kelantan 2 nd Regional Fluid Transfusion Workshop 10 February 2007

2. Outline Introduction Volume therapy in hemorrhagic shock Crystalloid versus colloid Hypertonic saline/Small volume resuscitation Blood Fluid therapy – when? How much? Fluid therapy in septic shock Endpoint of resuscitation

3. “ The Neglected Disease of Modern Society” Trunkey, DD

4. Trauma Chain of survival Fluid therapy is a part of the factors…

5. Polytrauma? A syndrome of combined injuries with ISS > 17 & consequent SIRS for at least 1 day, leading to dysfunction, or failure, of remore organs & vital systems, which themselves had not directly been injured. Marius Keel et al. Pathophysiology of trauma. Injury (2005) 36, 691-71

6. O2 flux = [ C.O X Hb X SaO2 X k] + [ C.O X PaO2 x 0.003] Principle of fluid therapy in Emergency care

7. Shock The viability & normal functioning of multiple organ systems & the whole body depends on continuos adjustment of C.O & DO2 to meet VO2 C.O   VO2 & DO2 imbalance = cumulative O2 debt Cumulative O2 debt overwhelms the physiologic reserve of CVS & RS to compensates = SHOCK Mohd Y Rady. Em. Med, 1996

8. Traumatic shock Tissue oxygenation is compromised by  DO 2 (hemorrhage) &  VO 2 (inflammatory response). Occurs in combination (bleeding, pain, tissue edema, neurogenic shock @ tension pneumothorax). Bleeding frequently occurs at multiple sites & is self limiting. Penetrating trauma, major bleeds rapidly leads to hypovolemic cardiac arrest

9. Marius Keel, Omar Trentz. Pathophysiology of polytrauma. Injury (2005) 36, 691 - 709

10. Pseudo-shock

11. Fluid Balance Consequences in Early Shock Mobilization of ECF Haemodilution of plasma – ?Coagulation effects – Gradual fall in Hb Maintenance of vascular space at the expense of the ECF

12. Late shock • Capillary leak • Loss of plasma volume • Tissue edema • Organ edema (lung, kidney) • Multiple organ failure

13. Phases of Resuscitation in Trauma Care Pre-hospital Resuscitation ED Resuscitation Establishment of Definitive Care ICU on going resuscitation

14. Aim of volume resuscitation • Early, complete restoration of tissue oxygenation • Minimal biochemical disturbance • Preservation of renal function • Avoidance of transfusion complications

15. Goals of Fluid therapy in hemorrhagic shock First Priority: Restore volume Second Priority: Restore blood - oxygen carrying capacity Third Priority: Normalize coagulation status

16. Fluid of choices Well-balanced resuscitation fluid resembling ECF Rapid volume expansion of IVS Sustained expansion No sugar

17. Options for fluid resuscitation Crystalloid – NS, Lactated Ringers’s solution, hypertonic saline Colloid – albumin, gelatine, dextran, starch (VOLUVEN) Blood – allogenic blood, autologous blood Blood substitutes – cross-linked, polymerize @ conjugated Hb

18. Optimal fluid resuscitation No ideal fluid resuscitation Combination therapy Volume expansion O2 carrying capacity of blood, without the need for cross matching @ the risk of transmission Restore & maintain the normal composition & distribution of body fluid compartment

19. Crystalloids • Ringer’s: – Low sodium, lactate load • Saline: – Hyperchloraemic acidosis, no K+ • Both: – Large volume resuscitation needed (3:1)

20. Crystalloid

21. Crystalloids Lower cost EC expander Greater urinary flow Replaces interstitial fluid Transient haemodynamic improvement (20 – 30 min) Peripheral oedema Pulm oedema (protein dilution +  PAOP)

22. Colloids Greater cost IV expander, do not resuscitate ECF Smaller volume (1:1) Osmotic diuresis Longer duration of persistence (2 – 8 hours) Less cerebral oedema Coagulopathy Pulm oedema (cap. leak state)  GFR (hyperoncotic kidney failure syndrome Improved rheology • Allergic risk (gelatin > dextran > HES)

23. Colloid (no capillary leakage)

24. Colloids versus crystalloids for fluid resuscitation in critically ill patients: The Cochrane review: Lancet; Issue 2 Oxford 2000 by Alderson P, Schierhout G, Roberts I, Bunn F Conclusion: No evidence that resuscitation with colloids reduces the risk of death compared with crystalloid in patient with traumatic injury

25. The crystalloid–colloid debate has evolved into a colloid-colloid debate

26. Ideal colloid National Research Council – USA (1963) Rapidly replaces blood volume losses. Restores the haemodynamic balance. Normalizes microcirculatory flow. Have a sufficiently long intravascular life. Be readily metabolized, readily excreted and well tolerated. Be free of side effects, especially regarding haemostasis and anaphylactoid reaction Be cost effective and contribute to blood savings.

27. Gelatins Short acting Prevent platelet aggregation induce by ristocetin - minimal effect on coagulation May be diuretic Allergy risk Contain high [Ca 2+ ) ~ facilitate clotting

29. Dextrans Good duration of effect Good rheological effect (esp Dextran 40) Allergy risk Significant coagulation effect May interfere with cross-match Dextran 40 can cause osmotic renal damage

30. Albumin Expensive • No evidence of benefit • Some evidence of harm • ANZICS SAFE study: – 7000 patients randomized to Alb or NS – Increased mortality with albumin (p<0.05) in trauma (more intracerebral bleeding)

31. Starches Good duration of effect High molecular weight starches impair coagulation Medium molecular weight HES has minimal effect Possible endothelial benefit

32. Hetastarch (hydroxyethyl starch) Derived from corn starch Modified natural polymers of amylopectin which breaks down by amylase  IV persistence due to substitution of hydroxyethyl group with D – glucose & more of glucose molecules hydroxylated at the C2 position versus the C6 position,

33. Hetastarch evolutionary concept A high degree of substitution (> 0.6), a high C2:C6 ratio (> 8), and a high initial MW (> 450 kDa) will maximize the intravascular half-life. Polymers with a MW < 50 kDa are eliminated rapidly by glomerular filtration and larger polymers are hydrolysed by amylase into smaller molecules.

34. HAES classification

35. Types of HES 1 st HES – marketed in US & Germany, 450kDa, a/w coagulopathy, withdrawn Elohes 6% - (200/0.62) Lomol 10% - (250/0.45) Haes – Steril 6% - (200/0.5) Voluven 6% - (130/0.4)

36. Advantages of HES Encourages the restoration of cell mediated function and macrophage function after hemorrhagic shock Schmand JF et al. Criti Care Med 1995;23:806–14. 10% HES (200:0.5) resulted in significantly better systemic haemodynamics and splanchnic perfusion than volume replacement with 20% human albumin Boldt J et al. Anesth Analg 1996;83:254–61.

37. HES & allergic reactions Laxenaire MC et al. Anaphylactoid reactions to colloid plasma substitutes: incidence risk factors mechanisms. Annales Francais d’Anesthesie et Reanimation 1994;13:301–10 A French multicenter prospective study.

38. Disadvantages of HES Repeated administration of HAES especially high in vivo MW – reduce factor VIII & VWF & renal function (coagulopathy & anuria) Haes – Steril solutions, medium MW were widely used for intravascular volume replacement in cardiac surgery. Recommended max dose per day: 20 – 33 ml/kg.

39. Voluven HES 130/0.4 was developed with the aim of improving the pharmacokinetic & Mw distribution profile of HES 200/0.5 Their beneficial effects appear to be related more to their action on inflammatory processes than their colloid osmotic power It has been shown in few pharmacokinetic studies that voluven solutions were decreased in plasma & tissue storage after repeated administration (50 – 75 ml/kg/d) & less influence on coagulation. Anest Analg 2003;96:936 – 43 Anesthesiology, V 99, No 1, Jul 2003

40. Hypertonic saline Stackford SR. J Trauma 1998:44:50-8 High osmolality (2400 mOsmol/L) Small Volume Resuscitation Reduced cerebral edema Reduced trauma-induced immuno-suppression CI: dehydration, oliguric renal failure, cardiogenic shock, DKA, coagulopathies or active hemorrhage Central pontine myelinosis : NO clinically significant & were not reported Practical dose: 200mls 7.5% NaCl in 10 min

41. Hypertonic Saline

42. Velasco IT et al. Hyperosmotic NaCl and severe hemorrhagic shock. Am J Physiol 1980;239:H664-73 Severely hemorrhaged dogs (40 ml/kg blood loss) re- sponded with a restored arterial pressure and cardiac output following IV bolus injections of 4 mL/kg of 7.5% NaCl, A volume equivalent to only 10% of the volume of shed blood

43. Best evidence Wade CE et al. Efficacy of hypertonic 7.5% saline and 6% dextran-70 in treating trauma: a meta-analysis of controlled clinical studies. Surgery 1997;122:609-16. 14 trials (1200 patients, 8 HSD, 6 HS) Conclusion: No differences in survival with HS, HSD, crystalloid

44. Best evidence Wade CE et al. Individual patient cohort analysis of the efficacy of hypertonic saline/dextran in patients with traumatic brain injury and hypotension J. Trauma 1997;42:S61-5. RCT comparing HSD & HS alone, as compared to crystalloid. Conclusion: some benefit of HS in penetrating injuries and those with combined shock and severe head injury.

45. Blood Oxygen flux: CO × O 2 content : CO(SaO2 × Hb × 1.34) Blood transfusion is reserved for cases of significant or ongoing bleeding. Why? - Limited blood supply - Need to be re warmed - Disease transmission - Immunosuppressive effect/ risk of infection - I ndependent risk factor for post-traumatic organ dysfunction.

46. Blood Limit transfusions Transfusion threshold < 7g/dl Maintenance level 7 – 9 g/dl Older patients and those with ischemic heart disease may need higher Hb

47. Alternative choices Autologous blood salvage technique Blood substitute - modified hemoglobins - perfluorocarbons

48. Autologous blood salvage technique Example: to reinfuse blood loss secondary to a massive hemothorax. Tedious & technical, need experienced personal Risk of bacterial contamination Micro emboli of platelet plugs and fractured red blood cells.

49. Artificial hemoglobin Sloan EP et al. Diaspirin cross linked hemoglobin (DCLHb) in the treatment of severe traumatic hemorrhagic shock. a randomized controlled efficacy trial. JAMA 1999; 282:1857-1864 Study terminated prematurely Increased number of death in the experimental group.

50. Hemoglobin based oxygen carrier HBOCs Analdo BD, Minei JP. Potential of hemoglobin based oxygen carrier in trauma patients. Curr Opin Crit Care 2001; 7: 431-436 Excellent overview relevant to trauma Problem: nitric oxide scavenging effects leading to smooth muscle constriction and subsequent blood pressure elevation

51. HBOC- 201 McNeil JD, Smith Ld, Jenkins DH, et al. J Trauma 2001; 50:1063-1075 Hypotensive resuscitation using a polymerized bovine hemoglobin-based oxygen carrying solution (HBOC- 201) leads to reversal of anaerobic metabolism.

52. Fluid resuscitation: WHEN & HOW MUCH? Traditional strategy: to restore patients to a normovolemic state ASAP Based on animal studies (1950 – 60) & Vietnam war. Recent strategy: judicious use of fluids, SVR Lack of randomized controlled studies, lack of implementation ? No documentation support the proposed changes actually will improve patient outcome

53. Treatment with IV fluids before hemorrhage was controlled increased the mortality rate, especially if the BP was elevated. Kowalenko T, Stern S, Dronen S, Wang X. Improved outcome with hypotensive resuscitation of uncontrolled hemorrhagic shock in a swine model. J Trauma 1992;33:349-53. Stern S, Dronen S, Birrer P, Wang X. Effect of blood pressure on hemorrhage volume and survival in a near- fatal hemorrhage model incorporating a vascular injury. Ann Emerg Med 1993;22:155-63.

54. Postulation Increased hydrostatic pressure driving ongoing bleeding or dislodging a clot, as well as the decrease in blood viscosity and dilution of clotting factors. - Shoemaker WC et al. Resuscitation from severe hemorrhage. Crit Care Med 1996;24:S12-23 . A caveat that also bears consideration when comparing such studies, is the anesthetic used, which can also significantly affect blood loss. - Soucy DM et al. Effects of anesthesia on a model of uncontrolled hemorrhage in rats. Crit Care Med 1995;23:1528-32.

55. SBP threshold Sondeen JL et al. BP at which rebleeding occurs after resuscitation in swine with aortic injury. J Trauma 2003;54:S110-7 Findings: SBP threshold = 90 mmHg, independent of time from start of bleeding.

56. Administering large quantities of IV fluids without controlling the hemorrhage results in hemodilution (  HCT,  available Hb (and oxygen- carrying capacity),  clotting factors & ECF compartment This effect is found regardless of the fluid used (blood, LR, NS, hypertonic saline). Hahn RG. The use of volume kinetics to optimize fluid therapy. J Trauma 2003;54:S155-8

57. The optimal volume of IV fluid administered is a balance between improving tissue oxygen delivery against increasing the blood loss by raising SBP MODS CLOTS Major controversy

58. Delayed fluid resuscitation in penetrating trauma Bickell WH et al. New Engl J Med 1994;331:1105-9. Randomized, prospective and blinded comparison of immediate versus delayed fluid resuscitation for hypotensive patients with penetrating torso injuries. Methods: Patients in the immediate resuscitation group received infusion of isotonic infusion of Ringer's acetate solution through two large bore IV catheters inserted at the scene.

59. Delayed fluid resuscitation in penetrating trauma Patients in the delayed resuscitation group also had two large bore IV catheters inserted at the scene but these were then flushed and capped. After arrival in the operating room, IV crystalloid and packed red cells were given to all patients to maintain SBP > 100 mm Hg, HCT > 25% and urine output > 50 ml per hour. The majority of patients were in hospital within 30 min of reported injury and entered the OR < 1H of hospital time.

60. Delayed fluid resuscitation in penetrating trauma 598 studied patients, 70 died before reaching the OR. Survival rate of delayed resuscitation group (70%) compared with that in the immediate resuscitation group (62%). The frequency of complications was similar in the two groups. Conclusion: In hypotensive patients with penetrating torso trauma, delay of fluid resuscitation until operative intervention improves outcome.

61. Regel et al, Acta Anaesthesiol.Scand., 1997 Data limited to penetrating injuries No evidence for blunt haemorrhagic trauma Decision on field resuscitation relates to type of trauma and likelihood of hospital transfer

62. On going debate/uncertainty Best practice for: Penetrating versus blunt trauma Rural versus urban settings Young versus older patients Head injured versus non head injured patients ? Malaysian Practice

63. Timing of resuscitation Do not delay transfer for resuscitation Priority is arrest of hemorrhage Commence aggressive resuscitation once control of bleeding is imminent Pepe et al Emerg.Med Clin.North Am., 1998

64. Pre-hospital resuscitation Søreide & Deakin, Injury, 2005 Set resuscitation targets according to type of trauma • Start isotonic crystalloid infusion – Rapid 500ml to achieve targets • Reassess after each fluid bolus • Do not delay transportation for other than life-saving maneuvers • Maintain care during transportation

65. Blunt Trauma Søreide & Deakin, Injury, 2005 • Goals: – Perfusion of vital organs without increasing bleeding • Minimal fluid resuscitation – Rapid infusion of rapid 500ml of isotonic crystalloid • Targets: – Restore peripheral pulses – Keep systolic arterial pressure < 90mmHg

66. TBI Søreide & Deakin, Injury, 2005 • Goals: – Limit bleeding risk – Maintain CPP • Moderate fluid resuscitation – Rapid infusion of rapid 500ml of isotonic crystalloid • Targets: – Restore and maintain SBP > 110mmHg

67. Penetrating injury Søreide & Deakin, Injury, 2005 • Goals: – Perfusion of at least brain and heart without increasing bleeding – Rapid transfer • Minimal fluid resuscitation – Rapid infusion of 500ml of isotonic crystalloid • Targets: – Restore basal cerebral perfusion – Keep systolic arterial pressure < 80mmHg

68. Søreide & Deakin, Injury (2005) 36, 1001 - 1010 Fluid resuscitation & blood transfusion in the Emergency Department are still essential elements of the early hospital management of critically ill injured patients

69. Rocha-e-Silva et al. CLINICS 60(2):159-172, 2005 Review paper: Small volume hypertonic resuscitation of circulatory shock. Conclusions: Safe, but cautious in moribund, or chronic debilitating diseases. First treatment for posttraumatic hypotension, particularly in penetrating trauma head trauma. Not a/w increased bleeding, clinically significant hypernatremia and allergic reactions Commercially available in European countries. A larger prospective, multicenter trials is required to better define the patient population to maximally benefit from hypertonic saline

70. SIRS (2 out of 4 criteria) with detection of bacterial focus ± /elevated CRP/elevated pro-calcitonin Septic shock: sepsis-induced with hypotension despite adequate fluid resuscitation along with the presence of perfusion abnormalities that may include, but not limited to lactic acidosis, oliguria or acute alteration of mental status Sepsis Crit Care Med 1992;20:864-74

71. Fluids in septic shock Marx et al. Int Care Med , 2002 • 25 fasted, ventilated pigs • Faecal peritonitis • Fluid titrated to keep CVP 12mmHg – Ringer’s solution (RS) – Modified fluid gelatin 4% (MFG4%) – Modified fluid gelatin 8% (MFG8%) – Hydroxyethyl starch 200/0.5 (HES) • Haemodynamics and oxygenation measured at 4 and 8 hours

72. Marx et al. Int Care Med , 2002 Fluid requirements

73. Cardiac output Marx et al. Int Care Med , 2002

74. Mixed S v O 2 Marx et al. Int Care Med , 2002

75. Acid base Marx et al. Int Care Med , 2002

76. Fluids in septic shock Marx et al. Int Care Med , 2002 Conclusions: Colloids were significantly better than Ringer’s for resuscitation in this model HES appeared to be slightly better than either isotonic or hypertonic gelatin

77. Sepsis • Goals: – Restore tissue perfusion rapidly • Aggressive fluid resuscitation – Rapid infusion of 500ml of isotonic crystalloid and colloid – Inotropic support as required • Targets: – Maintain ScvO2 > 70% – Keep systolic arterial pressure > 65mmHg

78. End point of resuscitation Traditional: Achieved definitive care New: Correction of O 2 debt as end point

79. Prehospital care, Arrival to ED Stabilization of vital signs Relieve tissue hypoxia Admission in ICU Phase 1 Phase 2 Phase 3 End point of Resuscitation of Shock

80. RADY ET AL • RESUSCITATION IN THE ED. AMERICAN JOURNAL OF EMERGENCY MEDICINE • Volume 14, Number 2 • March 1996 . End point of Resuscitation of Shock

81. End point of Resuscitation

82. Davis , Shackford. Base deficit as a guide to volume resuscitation. J. trauma 1988. Mild: -2 to -5, moderate: -6 to -14, severe: > -14 Worsening base deficit correlated with ongoing blood loss normal base deficit taken as end point of resuscitation

83. 76 patients Lactate normalized in 24 hr: 100 % survival, 24 – 48 hr 78 % survival, > 48 hr: 14 % survivors Serum lactate and time to normalization (less than or equal to 2 mmol/l) appears to be a suitable end point for resuscitation Abramson et al. Lactate clearance and survival following injury. J. Trauma . 1993

84. Bishop, Shoemaker & colleague J. Trauma 1995 Prospective randomized trial of survivors values of C.I, O 2 delivery and O 2 consumption as resuscitation end point in severe trauma Supranormal values Cardiac Index: CI > 4.5 L/min O 2 Delivery index: DO 2 I > 600ml/min/m2 O 2 consumption index: VO 2 I > 170 ml/min/m2

85. Bishop, Shoemaker & colleague J. Trauma 1995 50 patients on supranormal variables cf 65 control patients lower mortality ( 18 % Vs 37 % ) fewer organ failures per patient DO 2 I & VO 2 I are strong predictor of multiple organ failure and death Standard hemodynamic measurement MAP, CVP fail to differentiate between survivor and non- survivors.

86. Summary Severe hemorrhagic shock Aggressive versus judicious fluid therapy (inconclusive) Restrictive & permissive hypotension in uncontrolled hemorrhage (clinical evidence is still limited). Minimum resuscitation, stop the bleeding (surgical intervention) then maximum resuscitation. Future trend may be SVR with HS Ringer’s lactate @ NS/ ±Starch is an initial fluid of choice Red blood cells if HCT < 25. FFP, cryoprecipitate only for coagulation problems Septic shock Early goal directed, large volume therapy Starch is a fluid of choice

87. Conclusions Resuscitation should be seen as a continuum in which pre-hospital care, emergency room management and intensive therapy merge. Venous access & fluid therapy are a necessary part of this continuum but the optimum timing for fluid administration depends on the circumstances. Patient survival is linked to the overall quality, integration, communication & process of care in a trauma system.

88. THANK YOU