The Impact of Saline Flushing Through Different Sized PIVC Gauges on Endothelial Injury, Platelet Activation, and Coagulation: A Human Experimental Trial

Abstract

Up to 90% of peripheral intravenous catheters (PIVCs) fail and often result in post-insertion complications (such as thrombosis), causing pain and discomfort for the patient, delayed treatment, and additional health care costs. Current research suggests that the infusion rate/velocity of saline administered through different sized catheters may be capable of causing endothelial damage and platelet activation due to the shear stress/shear rate generated at the catheter tip. Therefore, this thesis sought to investigate whether flushing saline at clinical infusion rates of 1mL/sec through smaller sized PIVC gauges (i.e., 22G) causes greater endothelial injury, platelet activation and coagulation (i.e., thrombotic risk) than larger sized PIVC gauges (i.e., 18G). A total of 12 participants were bilaterally cannulated with an 18G and 22G PIVC. Both catheters were flushed hourly with 10mL of saline (0.9% NaCl) at a fixed infusion rate of 1mL/sec, over a 5hr period. Post saline infusion (i.e., fluid shearing of the cephalic vessel wall and blood), whole blood (WB) was collected at baseline (0hr), 1hr, 3hrs and 5hrs, to measure endothelial injury (tissue factor (TF) release), platelet activation (CD62p and PAC-1), and coagulation (activated partial thromboplastin time (aPTT)/prothrombin time (PT) and serum calcium (Ca2+)). A two-way repeated measures analysis of variance (RM-ANOVA) mixed effects model was used to determine whether catheter size and/or time significantly affected endothelial injury, platelet activation and coagulation. Normalized TF concentrations decreased from T=0hr (immediately after first saline flush; 2.94 ± 0.14 ag/μg) compared to T=1hr (2.87 ± 0.08 ag/μg; p=0.0208) and T=5hrs (2.88 ± 0.09 ag/μg; p=0.0226) when data was pooled from both catheter groups. The median fluorescent intensity for platelet CD62p increased from T=0hr (117.0 ± 27.7) compared to T=1hr (150 ± 32.0; p<0.0001) and T=3hrs (144.3 ± 30.6; p=0.006) in blood collected from the 22G PIVC. The median fluorescent intensity for platelet CD62p also increased from T=0hr (115.4 ± 26.6) compared to T=1hr (140.2 ± 30.0; p=0.0094) and T=3hrs (141.7 ± 23.4; p<0.0001) in blood collected from the 18G PIVC. However, there were no significant catheter or time-induced effects for PAC-1 expression, nor did an interaction between catheter size and time on PAC-1 expression exist (all p>0.05). There were also no significant catheter or time-induced effects for aPTT/PT and serum Ca2+, nor did an interaction between catheter size and time on aPTT/PT and serum Ca2+ exist (all p>0.05). This thesis demonstrated that flushing 10mL of saline at a fixed infusion rate of 1mL/sec through both catheters induces a significant decrease in TF release at 1hr and 5rs, and a significant increase in platelet CD62p expression at 1hr and 3hrs, when compared to 0hrs (first flush). These data indicate that flushing saline through larger (i.e., 18G) and smaller (i.e., 22G) sized PIVC gauges likely induces local endothelial injury/irritation followed by subsequent platelet adhesion/activation. These data likely suggest that the acute initiation of platelet activation could be followed by local thrombosis at a later stage, contributing to PIVC failure. Cumulatively, this thesis suggests that PIVCs should be flushed at a rate below 1mL/sec, and that further studies are required to clearly define safe, non-injurious flushing velocities for implementation into clinical guidelines to improve clinical care and cost-efficiencies within the health sector.