Resuscitation strategy

vere vasodilatory shock. Abid and colleagues

demonstrated

These data strongly support a haemodynamically-guided fluid resuscitation strategy in patients with severe sepsis and septic shock. Furthermore, from an evolutionary point of view, humans have evolved to deal with hypovolemia and not hypervolemia. Large fluid boluses may counter the life preserving homeostatic

mechanisms in unstable critically ill patients, increasing the risk of death.123In some patients, hypotension and tachycardia do resolve with limited fluid resuscitation. It is likely that many of these patients have super-added dehydration as a result of poor oral intake and a delay in seeking medical attention. How-

ever, fluids alone will not reverse the haemodynamic instability of patients with more severe sepsis; in these patients, fluids alone are likely to exacerbate the vasodilatory shock and increase the capillary leak and tissue oedema. Based on these data, the initial resuscitation of patients with septic shock should logically include at most 500 ml boluses of crystalloid (Ringer’s lactate), to a

maximum of about 20 ml kg−1.124 Ideally, fluid resuscitation

should be guided by the determination of fluid responsiveness.5051Normal saline is an ‘unphysiologic’ solution that should be avoided, except in patients with acute neurological injuries. Nor- mal saline causes a hyperchloraemic metabolic acidosis125–128; it decreases renal blood flow63increasing the risk of renal failure.129In patients with sepsis, the use of normal saline as compared with physiologic salt solutions, has been associated with an increased risk of death.130Similarly, synthetic starch solutions increase the risk of renal failure and death in patients with sepsis and should be avoided.131132

The septic patient with an intra-abdominal catastrophe, who requires urgent surgical intervention, represents a sub-group of patients that may require more aggressive fluid resuscitation. However, overly aggressive fluid resuscitation will likely result in intra-abdominal hypertension, which is associated with a

high risk of complications and death.133 134 In these patients

continuous SV monitoring is essential and ongoing fluid requirements should be guided by the trend in the SV and the haemodynamic response to a mini-fluid bolus. In addition, peri- operative, intra-abdominal pressure monitoring is required in these patients.133

Norepinephrine should be initiated in those patients who re- main hypotensive (MAP < 65 mm Hg) despite this initial, limited fluid strategy.124135Norepinephrine increases arterial vascular tone increasing bp and organ blood flow. Venous capacitance vessels are much more sensitive to sympathetic stimulation than are arterial resistance vessels, consequently low dose α-1

agonists cause greater veno- than arterio-constriction.136In sep-

tic patients, α-1 agonists mobilize blood from the unstressed reservoirs in the splanchnic circulation and skin, thereby increasing venous return and cardiac output. In a porcine endo- toxic shock model, Datta and Magder137demonstrated that nor- epinephrine increased the MCFP, leading to an increase in venous return. Similarly in patients with septic shock, Persichini and col- leagues138demonstrated that deceasing the dose of norepineph- rine, decreased the MCFP with a decrease in venous return and cardiac output. In a cohort of patients with septic shock Kozieras and colleagues139 demonstrated that norepinephrine increased

that the early use of norepinephrine in patients with septic

shock was a strong predictor of survival. These studies demon- strate that in patients with septic shock, the early use of norepin- ephrine restores the stressed blood volume, increasing the MCFP, venous return and cardiac output. The increase in the stressed blood volume is as a result of the mobilisation of blood, rather than the short-lived effect of a volume expander. Therefore un- like fluids, the effect of α-1 agonists on venous return is enduring and not associated with tissue oedema. α-1 agonists should not be used in patients with hypovolaemic shock (e.g. cholera) who are already venoconstricted; in this setting, α-1 agonists will cause severe vasoconstriction, impairing organ blood flow. How- ever, in septic veno- and arterio-dilated patients, α-1 agonists in-

crease venous return, increase stroke volume and increase arterial tone, thereby increasing organ blood flow.142–144Digital and limb ischaemia and ischaemic skin lesions are extremely rare with the use of norepinephrine,145occurring usually with high dosages and usually when used together with vasopres- sin.146147Furthermore, uncontrolled disseminated intravascular coagulation (DIC) plays a contributing role in these patients.148We are unaware of any reported patients with digital or limb ischaemia associated with the early use of norepinephrine. In our experience the early use of norepinephrine appears to reduce the peak and total dose of vasopressors administered. It is noteworthy that norepinephrine may be safely given through a well-functioning peripheral venous catheter,149precluding the requirement for emergent central venous catheterization, which is generally regarded as an obstacle to the early use of norepinephrine. In experimental sepsis models, norepinephrine appears preferable to epinephrine and phenylephrine as a first-line therapy in restoring haemodynamic stability.150151Dopamine as opposed to norepinephrine is associated with an increased risk of arrhythmias and death in patients with sepsis and should be avoided.152–154

Conclusions

An emerging body of basic science and clinical studies supports the concept of a haemodynamically-guided, restricted fluid re- suscitation strategy in patients with severe sepsis and septic shock. Initial fluid resuscitation should be limited and guided by an assessment of fluid responsiveness. Norepinephrine in- creases preload, systemic vascular resistance and cardiac output and its use in patients with persistent hypotension is recom- mended early in the course of septic shock. Early bedside echo- cardiographic assessment of cardiac function is recommended to guide further haemodynamic management. Adequately powered, randomized, controlled trials, are urgently required to demonstrate the benefits of the early use of norepinephrine and a conservative, haemodynamically-guided fluid resuscita- tion strategy.

Date: 2016-04-22; view: 693