Cementerio Poniente

Findings of worse outcomes associated with impaired microvascular flow in sepsis have prompted investigations of therapeutic interventions to counteract these changes. Almost invariably, the first step in the treatment of a shocked patient is the administration of intravenous fluid. Traditionally fluid resuscitation has been targeted to macrocirculatory variables but the optimal target for fluid resuscitation remains unclear and the impact of fluids on the microcirculation is poorly understood. It is likely that fluids influence microvascular flow in a number of ways. The most obvious is enhanced filling of the vasculature leading to greater forcing pressures resulting in enhanced microvascular flow. Fluids will also change the haemorheology of blood with effects varying according to the type of fluid.126 It has also been shown that excessive haemodilution can reduce regional tissue oxygenation by causing shunting in the microcirculation.127 Fluid resuscitation has been shown to improve sublingual microvascular blood flow in two clinical studies of patients with septic shock.128,129 In the first of these studies,128 improvements in perfused vessel density were found in those patients with ‘early’ sepsis (less than 24 hours after diagnosis of severe sepsis) but not in those with ‘late’ sepsis (more than 48 hours after

diagnosis). There were no associated changes in global haemodynamics. The second study investigated the effects of passive leg raise and fluid boluses on macrohameodynamics and microvascular flow in patients within 24 hours of their ICU admission for sepsis.129 These investigators found increases in cardiac ouput and improvements in microvascular flow associated with both passive leg raise and volume expansion.

The choice of fluid for resuscitation will also influence acid-base status, with solutions containing high chloride concentrations, such as 0.9% saline, resulting in a reduction of strong ion difference and metabolic acidosis. 0.9% saline appears also to have deleterious effects on the microcirculation and organ function.14,130 Choice of resuscitation fluid may also modulate the inflammatory process in critical illness. Saline has been implicated in worsening the pro-inflammatory insult, whereas there is limited data suggesting that certain colloids dissolved in balanced solutions may help to ameliorate the pro- inflammatory response.131,132 Colloids have also shown improved microvascular flow compared to saline in a variety of experimental models using intravital microscopy to directly observe leucocyte – endothelial interaction.133,134 Some reports suggest that the use of crystalloids for resuscitation may impair microvascular flow and cause fluid shifts into the interstitium.135,136 Increased diffusion path length alongside poor oxygen solubility in aqueous solutions may then result in a reduction in oxygen availability to the cells. In general, clinical trials have shown improved microvascular flow associated with colloids (in particular starches) compared to crystalloids. Two prospective randomised studies comparing crystalloid and colloid (hydroxyethyl starches) in perioperative patients using gastric tonometry found improved gastric perfusion associated with starches.137,138 A recent study by Dubin and colleagues, found that fluid resuscitation with 6% HES 130/0.4

caused a greater improvement in sublingual microvascular flow and perfused vessel density assessed using SDF imaging compared to saline resuscitation in a group of patients with early sepsis.139 Comparing gelatins to starches has given mixed results, with some investigators finding improvements in gastric perfusion 140,141 whilst others found no difference.142 A prospective randomised trial of a ‘balanced’ (plasma adapted) starch solution versus starch suspended in 0.9% saline found improved gastric perfusion using the ‘balanced’ starch.143 Hypertonic saline used for the treatment of hypovolaemic shock has been shown to increase microvascular blood flow and perhaps reduce endothelial cell oedema.144 Despite these findings, a recent large pragmatic multicentre trial of colloid (albumin) versus crystalloid (0.9% saline) as fluid resuscitation in a hetergeneous group of critically ill patients demonstrated no difference in outcome.145 It appears that choice of fluid type amongst clinicians will continue to vary (‘colloid vs crystalloid debate’).

There is little data describing the effects of fluid resuscitiation aimed at macrohaemodynamic goals on microvascular flow. Hiltebrand, Kimberger and colleagues published two papers in March 2009 investigating the effects of goal directed fluid therapy in a porcine model of surgery. In the first of these papers, 27 pigs underwent open laparotomy.146 They were randomly assigned to one of three treatment groups. All groups received Ringer’s lactate (RL) at 3ml/kg/hour. The ‘restrictive’ group (R-RL) received no further fluid, the goal directed RL group (GD-RL) received 250ml boluses of RL, and the goal directed colloid group (GD-C) received 250ml boluses of 6% hydroxyethyl starch (130/0.4). The boluses were given when mixed venous saturations fell to below 60%, although there was a ‘lockout’ period of 30 minutes. This group found improvements in global haemodynamics and regional blood flow assessed by mesenteric artery flow in both the GD-RL and GD-C groups compared to the R-RL group. Microcirculatory flow in the

intestinal mucosa assessed by laser Doppler increased in the GD-C group but was unchanged in the other groups. Similarly, tissue oxygen tension assessed by intramural Clark type electrodes increased in the GD-C group, remained unchanged in the GD-RL group and fell in the R-RL group. The authors concluded that GDHT using colloid improved microcirculatory blood flow in the small intestine. A further study that included the addition of a hand sewn colonic anastomosis investigated the changes in microvascular flow and oxygenation in healthy and anastomotic colon.147 With exactly the same treatment groups, they found a significant increase in tissue oxygenation and microvascular flow in the healthy and injured (anastomotic) colon in the colloid goal directed group compared to the crystalloid goal directed and restrictive groups.