**3. Fluid resuscitation of septic shock patient**

Crystalloid intravenous fluid either ringer lactate or 0.9% normal saline is the first and the main step in restoring hemodynamic instability. Septic shock patient in the initial stage should be considered fluid responsive and receive fluid bolus [52]. Not all septic shock patient will respond to the initial fluid resuscitation, hence additional pharmaceutics intervention is needed to augment of fluid resuscitation to restore the hemodynamic and improve organ perfusion [53, 54]. Fast intravenous (IV) crystalloid infusion has a slower redistribution rate. Interstitial distribution is hypothesized to be greater in sepsis than in healthy volunteers due to sepsis pathophysiology [55] (**Figure 1**). The maximal effect of IV crystalloid bolus achieves at one minute and return to baseline after 30 minutes. Only one third of septic shock patient will have risen in MAP after fluid challenge [56, 57]. Amount of IV fluid resuscitation in patients with septic shock is not known. In one retrospective study found large amount of fluid more than 5 liter per day associated with increase mortality rate and need of ventilatory support [58, 59]. 50% 0f septic shock patients will be non-fluid responsive, where a condition where the administration of more fluid bolus may lead to fluid accumulation, impaired oxygen delivery, and worsening hypoperfusion [60]. How fast fluid should be administered in septic shock resuscitation is not known. Mainly retrospective studies shows failure to complete 30 mL/kg of IV crystalloid over 3 hours was associated with increased mortality [61]. In multi-center study found IV fluid administration within six hours was associated with decreased mortality [62]. regarding type of fluid in resuscitating septic shock patient, the current guideline recommends both sodium chloride and balanced crystalloids [20]. Studies within the critically ill have shown lower risk of in-hospital or 30-day mortality, AKI, or major adverse kidney event in the first 30 days with the use of balanced crystalloids over sodium chloride solutions [63, 64]. SMART trial, compared the two solutions in 15,802 critically ill patients, reported a lower rate of death from any cause, renal-replacement therapy, or renal failure with using balanced crystalloids versus normal saline [63]. In secondary analysis of SMART study among 1,641 patients were admitted to the medical ICU with a diagnosis of sepsis, balanced crystalloids was associated with a lower 30-day in-hospital mortality rate, renal failure, and a higher number of vasopressor free days compared with use of saline [64]. Amount of fluids resuscitation should be decided to minimize the complication of over resuscitation as pulmonary edema, brain edema, abdominal compartment syndrome and third space edema which will lead resulting in end-organ hypoperfusion by decrease oxygen delivery, capillary blood flow and lymphatic drainage. Which explain worse outcomes in shock with a positive fluid balance [55, 65, 66]. Collapsible inferior vena cava can along with other hypoperfusion indices can be used to monitor fluid and resuscitation of septic shock patient [67]. Resuscitation of septic shock patient with high volume of normal saline is associated with hyperchloremia, AKI, multiorgan dysfunction, and high mortality [68, 69]. Fixed amount of fluid hardly suitable for all septic shock patients, Teboul and Monnet proposed to administer crystalloid about 10 mL/ kg within the first 30 to 60 min and monitor patient [52]. If patient develop any signs of respiratory failure stop further boluses. In case CRT is still prolonged, tachycardia or low blood pressure reading, skin mottling increase in the infusion rate [70].

*Perfusion indices should be used to individualize fluid administration approach in balanced crystalloid is recommended over normal slain in septic shock resuscitation.*
