Kimble R. Dunster

Sepsis is a multi-system syndrome that remains the leading cause of mortality and critical illness worldwide, with hemodynamic support being one of the cornerstones of the acute management of sepsis. We used an ovine model of endotoxemic shock to determine if 0.9% saline resuscitation contributes to lung inflammation and injury in acute respiratory distress syndrome, which is a common complication of sepsis, and investigated the potential role of matrix metalloproteinases in this process. Endotoxemic shock was induced in sheep by administration of an escalating dose of lipopolysaccharide, after which they subsequently received either no fluid bolus resuscitation or a 0.9% saline bolus. Lung tissue, bronchoalveolar fluid (BAL) and plasma were analysed by real-time PCR, ELISA, flow cytometry and immunohistochemical staining to assess inflammatory cells, cytokines, hyaluronan and matrix metalloproteinases. Endotoxemia was associated with decreased serum albumin and total protein levels, with activated neutrophils, while the glycocalyx glycosaminoglycan hyaluronan was significantly increased in BAL. Quantitative real-time PCR studies showed higher expression of IL-6 and IL-8 with saline resuscitation but no difference in matrix metalloproteinase expression. BAL and tissue homogenate levels of IL-6, IL-8 and IL-1β were elevated. This data shows that the inflammatory response is enhanced when a host with endotoxemia is resuscitated with saline, with a comparatively higher release of inflammatory cytokines and endothelial/glycocalyx damage, but no change in matrix metalloproteinase levels.

Extracorporeal membrane oxygenation (ECMO) delivers cardiac and/or respiratory support to critically ill patients who have failed conventional medical therapies. If the large-bore cannulas used to deliver ECMO become infected or dislodged, the patient consequences can be catastrophic. ECMO cannula-related infection has been reported to be double the rate of other vascular devices (7.1 vs 3.4 episodes/1000 ECMO days respectively). The aim of this study was to assess the ability of cyanoacrylate tissue adhesive (TA) to inhibit bacterial growth at the ECMO cannulation site, and the effectiveness of TA and securement devices in securing ECMO cannulas and tubing. This in vitro study tested the (1) antimicrobial qualities of TA against standard transparent dressing with ECMO cannula; (2) chemical compatibility between cannula, TA and removal agent; (3) pull-out strength of transparent dressing and TA at the cannula insertion site; and (4) pull-out strength of adhesive bandage and commercial sutureless securement devices (SSDs) on circuit tubing. Fisher’s exact test was used to evaluate differences in bacterial growth observed between the transparent dressing and TA groups. Data from mechanical testing were analysed using one-way ANOVA, followed by Tukey’s multiple comparison test or t test as appropriate. Statistical significance was defined as p < 0.05. No bacterial growth occurred under TA-covered cannulas compared with transparent dressing-covered cannulas (p = 0.002). Compared to plates lacking TA or transparent dressing, growth was observed at the insertion point and under the dressing in the transparent dressing group; however, no growth was observed in the TA group (p = 0.019). TA did not weaken the cannulas; however, the TA removal agent did after 60 min of exposure, compared with control (p < 0.01). Compared with transparent dressing, TA increased the pull-out force required for cannula dislodgement from the insertion point (p < 0.0001). SSDs significantly increased the force required to remove the tubing from the fixation points compared with adhesive bandage (p < 0.01). Our findings suggest that the combined use of TA at the cannula insertion site with a commercial device for tubing securement could provide an effective bedside strategy to prevent or minimise infection and line dislodgement.

Extracorporeal membrane oxygenation (ECMO) is a life-saving modality used in the management of cardiopulmonary failure that is refractory to conventional medical and surgical therapies. The major problems clinicians face are bleeding and clotting, which can occur simultaneously. To discern the impact of pulmonary injury and ECMO on the host’s haemostatic response, we developed an ovine model of smoke-induced acute lung injury (S-ALI) and ECMO. The aims of this study were to determine if the ECMO circuit itself altered haemostasis and if this was augmented in a host with pulmonary injury. Twenty-seven South African meat merino/Border Leicester Cross ewes underwent instrumentation. Animals received either sham injury (n = 12) or S-ALI (n = 15). Control animal groups consisted of healthy controls (ventilation only for 24 h) (n = 4), ECMO controls (ECMO only for 24 h) (n = 8) and S-ALI controls (S-ALI but no ECMO for 24 h) (n = 7). The test group comprised S-ALI sheep placed on ECMO (S-ALI + ECMO for 24 h) (n = 8). Serial blood samples were taken for rotational thromboelastometry, platelet aggregometry and routine coagulation laboratory tests. Animals were continuously monitored for haemodynamic, fluid and electrolyte balances and temperature. Pressure-controlled intermittent mandatory ventilation was used, and mean arterial pressure was augmented by protocolised use of pressors, inotropes and balanced fluid resuscitation to maintain mean arterial pressure >65 mmHg. Rotational thromboelastometry, platelet aggregometry and routine coagulation laboratory tests demonstrated that S-ALI and ECMO independently induced changes to platelet function, delayed clot formation and reduced clot firmness. This effect was augmented with the combination of S-ALI and ECMO, with evidence of increased collagen-induced platelet aggregation as well as changes in factor VIII (FVIII), factor XII and fibrinogen levels. The introduction of an ECMO circuit itself increases collagen-induced platelet aggregation, decreases FVIII and von Willebrand factor, and induces a transient decrease in fibrinogen levels and function in the first 24 h. These changes to haemostasis are amplified when a host with a pre-existing pulmonary injury is placed on ECMO. Because patients are often on ECMO for extended periods, longer-duration studies are required to characterise ECMO-induced haemostatic changes over the long term. The utility of point-of-care tests for guiding haemostatic management during ECMO also warrants further exploration.