Hemorrhagic Shock Clinical Trial
Official title:
The Clinical Efficacy and Safety of a Proprietary Solution Containing Hypertonic Sodium Lactate (Totilac®) Infusion for Resuscitation of Patients With Hemorrhagic Shock Due to Multiple Injuries
Indication: Resuscitation in pts with hemorrhagic shock due to multiple injuries
Prospective, open label RCT in pts. with traumatic hemorrhagic shock in RS Hasan Sadikin
Hospital, Indonesia.
PI: Dr. Kiki Lukman, PsBD(K), Surgery, RSHS. Co-PI: (late)Prof. Xavier Leverve MD, PhD,
Directeur, INSERM-E0221-Bioenergetique Fondamentale et Appliquée Université Joseph Fourier,
France
Hemorrhagic shock is a cause of death in trauma.Fluid resuscitation to ensure stable
hemodynamics and microcirculation by rapidly restoring circulating plasma volume could be a
cornerstone of managing trauma patients. Excessive fluid accumulation particularly in the
interstitial tissue should be avoided. Hypertonic solution shows promise in restoring
intravascular volume expansion and microcirculation with less fluid infusion in hypovolemic
patients. This study investigated efficacy and safety of hyperosmolar Na lactate(Totilac®)
for resuscitating traumatic hemorrhagic shock patients.
Patients with multiple injuries with grade III hemorrhagic shock and RTS ≥4 received std
initial fluid resuscitation of upto 2 liters of isotonic crystalloid. They also got similar
dose of either hyperosmolar Na lactate or ringer's lactate. Hemodynamic status, fluid
balance and and safety was recorded during the study.
Trauma is still an important cause of death and disability worldwide.Trauma patients often
experience fluid deficits. In addition to apparent blood loss, fluid deficit might also
occur secondary to generalized alterations of the endothelial barrier, resulting in diffuse
capillary leakage and fluid shift from the intravascular to the interstitial compartment.
Severe volume deficits after trauma result in hemorrhagic shock that further leads to the
decrease of tissue perfusion, especially to vital organs and inadequate delivery of oxygen
and nutrients necessary for normal tissue and cellular function. Subsequently, inadequate
and inappropriate management of hemorrhagic shock frequently results in the development of
post trauma multiple organ failure which increases the morbidity and mortality of the
patients. Consequences of hypovolemic shock (hemorrhagic shock) due to bleeding are one of
the major causes of death in trauma patients. Therefore, fluid replacement to reverse shock
and to restore perfusion to vital organs appears to be fundamental in the management of the
trauma patient, after ensuring an adequate airway, oxygenation and ventilation.
Effective control of hemorrhage and adequate intravenous fluid administration to restore
intravascular volume and maintain the tissue perfusion is crucial for saving the patient's
life and resuscitation can exacerbate cellular injury caused by hemorrhagic shock, if
resuscitation is not performed properly. The type of fluid used for resuscitation plays an
important role in this injury pattern. However, when, how and which fluids are ideal in
regards to fluid resuscitation remains controversial. The concept that early, aggressive
large - volume resuscitation by administration of isotonic crystalloids in volumes 2 to 3
times the estimated blood loss has been widely accepted and practiced; it has even became
the standard-of-care adopted by the ATLS for the treatment of trauma casualties (ATLS
congress). In patients with prolonged hemorrhagic shock frequently associated with
interstitial fluid deficits in addition to intravascular blood volume, resuscitation fluids
were needed to replace the intravascular volume loss and replenish interstitial deficits. It
has been suggested that aggressive fluid resuscitation improved survival with better
function of patient's vital organ patient's with less frequent renal failure. However,
aggressive fluid resuscitation can lead to fulminant pulmonary failure "Acute Respiratory
Distress Syndrome (ARDS)" and appears as an early cause of death after severe hemorrhage.
Moreover, it was observed that aggressive fluid resuscitation in uncontrolled hemorrhagic
shock to attempt to increase blood pressure to normal resulted in increased bleeding from
injured vessels, hemodynamic decompensation, and increased mortality, and led to cellular
injury when compared to no fluid resuscitation or hypotensive resuscitation (permissive
hypotension). Therefore a novel resuscitation strategy that overcomes those issues in the
near future is still required.
Hyperosmolar solutions of various concentrations (1.8%-7.5%) have been investigated as
resuscitation solutions in vitro, as well as animal and clinical studies, with promising
results. Clinical and experimental studies have demonstrated that small volume of hypertonic
saline solution is able to restore hemodynamics in traumatic shock patients. Small volume of
hypertonic solutions stabilize arterial pressure and cardiac output, improve microvascular
flow (increases renal, mesenteric, total splanchic and coronary blood flow), control
intracranial pressure, with no deleterious effects on immune functions. Moreover, in
hemorrhagic shock models, Hyperosmolar solution has immunomodulatory effects including
attenuation of immune-mediated cellular injury, modulating the post-trauma immune response,
decreasing neutrophil excitation, decreasing inflammation, neutrophil-endothelial binding,
lung damage, and bowel injury. This hypertonic solution was more effective than isotonic
crystalloids in minimizing the inflammatory response (especially neutrophil cyto-toxicity)
and in preventing lung and liver reperfusion injury, as well as in improving intestinal
blood flow. Improved survival rate in traumatic hemorrhagic shock patients treated with
hypertonic solution were reported in several trials. The beneficial effect of hypertonic
saline has been shown related to its hypertonicity characteristic.
A proprietary solution containing hyperosmolar sodium lactate (Totilac) is a hyperosmolar
solution with a physiological concentration of potassium chloride and calcium chloride.
Totilac with small volume administration during volume deficits in post cardiac surgery
patients improves cardiac output, oxygen delivery, urine output, attenuates metabolic
acidosis and maintains stable hemodynamic better compared to isotonic crystalloid.
Administration of small dose of Totilac in patients with dengue shock syndrome also improved
hemodynamic status and microcirculation. High lactate content in this solution offered more
benefit in shock patients when compared to other hypertonic solutions as lactate has been
known to act as energy substrate in mitochondrion containing cells and can be easily
metabolized in hypoxia. Hypertonicity related effects of hyperosmolar sodium lactate
solution in addition to lactate effect may offer at least similar benefits in hemorrhagic
shock patients, though until now there is no clinical study conducted to prove efficacy of
Totilac in hemorrhagic shock. This study aimed to evaluate the efficacy and safety of
Totilac as resuscitative fluid regimen in traumatic shock hemorrhagic patients.
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Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
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