**2.1 Heart rate**

Tachycardia is common sign of septic shock, and it predicts poor prognosis of septic shock patient. It is caused by stimulation of α- and β-adrenergic receptors increases in response to venodilattion and could be also related high temperature. Tachycardia is a sign impaired arterial tone [12]. It increases oxygen consumption, decreases diastolic filling and coronary perfusion, and increases arrhythmia [13]. Patients with septic shock and persistent tachycardia despite resuscitation measures has high mortality and morbidity rate [14].

#### **2.2 Blood pressure**

Blood pressure is easy to measure and monitor. Blood pressure is determined by cardiac output, systemic vascular resistance, and arterioles pressure and coronary perfusion and heart flow depend upon diastolic arterial pressure (DAP) [15].

*Assessment and Management of Hypoperfusion in Sepsis and Septic Shock DOI: http://dx.doi.org/10.5772/intechopen.98876*

Hypotension reflects decrease cardiac output, but it could be a delayed sign of hypoperfusion, and its absence does not necessarily rule out hypoperfusion. Hypotension triggers resuscitation. Low diastolic arterial pressure, in septic shock indicates impaired arterial tone. Optimizing blood pressure is one of the goals of fluid resuscitation and associated with better outcome [16]. Prolonged hypotension, low mean arterial pressure (MAP) and DAP associated with high mortality in septic shock patient [17, 18]. Normal MAP and DAP should be targeted to improve survival of septic shock patients [15]. No evidence what the best target level of DBP is but common approach is to titrate vasopressors in septic shock to keep DAP ≥50 mmHg [19]. Resuscitation should target MAP of 65 mmHg per the septic shock guidelines [20]. Hypoperfusion may persist even when pressure is restored so personalization approach to target blood pressure should consider other indices of perfusion [21].

### **2.3 Skin changes**

Skin examination including its color, blanching and worminess is one of the most important physical examination to determine level of skin perfusion which reflect vital organ perfusion. Anterior aspect of the knee is one body area that commonly examined for skin perfusion Mottling score is one of indices of hypoperfusion and associated with worse outcome regardless of vasopressor use [22, 23]. Normalization of skin color and disappearance of mottled skin are targets of resuscitation and related to higher survival rate of septic shock patient [24, 25].

### **2.4 Skin temperature**

Skin temperature is one of the most accessible markers of skin perfusion and hence tissue perfusion [26]. Hypothermia in circulatory shock is associated with impaired outcome [27].

### **2.5 Capillary refill time (CRT)**

CRT is the time taken to regain distal capillary bed color after blanching by pressure. Normally should be less than 3 seconds. It has been shown in in study of 783 critically ill patients that CRT is sensitive sign of decrease cardiac output measured by echocardiogram [28]. Capillary refill time is one of the best indices of adequate perfusion [29, 30]. And could be used as screening tool to predict sick patient that might need admission to critical care area. In one study, CRT and lactate are similar in predict survival [31]. In other study prolonged CRT associated with decrease perfusion of the liver, kidneys, gut and spleen [32]. CRT more than 4 seconds associated with higher mortality rate of septic shock patients [33]. In a randomized controlled study of septic shock patients with high lactate level but with a normal CRT had lower day-28 mortality when compared to prolonged CRT and high lactate level and survival of patients is higher with when resuscitation is guided by capillary refill time but not lactate levels [34]. When CRT used as index as optimal resuscitation it led to decrease mortality rate and should be used to guide fluid resuscitation in septic shock patient [34–36]. Septic shock patients failing to normalize their CRT after the first fluid bolus in ED had high mortality [37].

#### **2.6 Passive leg raise**

Passive Leg Raise (PLR) Can assist in identifying preload dependence. Utilization of the passive leg raise as index of resuscitation lead to reduce net fluid balance, acute kidney injury and pulmonary edema and may improve outcomes [38].

PLR became more popular and easier to use in different sitting including emergency department sitting [39].

By moving the patient from a semi-recumbent position, lowering the trunk and raising the patient's legs to 45°, an amount of ~300 mL of blood is transferred to the ventricles, thereby increasing the cardiac preload. If CO increases of at least 10% compared to baseline, the patient is considered preload responsive, thus capable of displaying a CO increase following administration of fluid. The change in cardiac output changes in is measured by thermodilution, echocardiography, pulse contour analysis or pulse pressure variation. Passive leg rising is shifts venous blood from the legs to the intrathoracic compartment. This response can predict the response to a fluid challenge. Passive leg-raise test is accurate and has excellent sensitivity and specificity, for that it is recommended to determine fluid responsiveness [20, 40]. A meta-analysis of 21 studies and 991 adult patients showed that a 10% 2% increase in cardiac output with PLR predicted fluid responsiveness [41].

#### **2.7 Urine output**

Oliguria which is urine output less than 0.5 ml/kg/hour is one of the main triggers for fluid challenges in septic shock patient [16]. Oliguria is one of signs of acute renal failure which is an independent risk factor associated with increased mortality during sepsis. Low UOP may reflect low renal perfusion pressure. UOP 30–50 mL/h in adult patient with septic shock should prompt further fluid resuscitation or other measures to increase cardiac output in a non–fluid-responsive patient [42]. UOP should not be taken alone as fluid resuscitation may not increase urinary output and cause positive fluid balance in patients with septic shock [20].

#### **2.8 Central venous pressure (CVP)**

Venodilation and hypovolemia cause decrease in ventricular preload which is signaled by decrease in central venous pressure. CVP reflect the right atrial pressure [43]. CVP alone is a poor variable to predict fluid responsiveness [44, 45]. The target CVP is <6–8 mmHg in spontaneous breathing patient and > 12–15 mmHg in mechanically ventilated patient [46].

#### **2.9 Lactate**

Lactates reflect the onset of anaerobic metabolism. In experimental conditions, lactate increases when oxygen consumption increased and oxygen delivery decreased. Lactate also elevated in beta-adrenergic stimulation, leading to an accelerated glycolysis and liver failure. Lactate >2 mmol/L associated tissue hypoperfusion (lactate >2 mmol/L) [47]. Clinical studies show high lactate levels are associated with a high mortality, independently of its cause [48]. Lactate is easy to measure and can be used in emergency department triage and as a goal of early sepsis therapy [49]. Repeating lactate measurements is a trigger of resuscitation [20]. Lactate-guided resuscitation has emerged after the observation that the higher the decrease in lactate levels, the best the outcome [50].

*Indices of hypoperfusion are combinations of pressure and flow measurements and clinical markers. They should be taken together and not to rely only on one index to diagnose and mange hypoperfusion* [51].
