Worthington G. Schenk

Fibrin Sealant Improves Hemostasis in Peripheral Vascular Surgery: A Randomized Prospective Trial

ObjectiveTo evaluate the efficacy and safety of an investigational fibrin sealant (FS) in a randomized prospective, partially blinded, controlled, multicenter trial. Summary Background DataUpper extremity vascular access surgery using polytetrafluorethylene (PTFE) graft placement for dialysis was chosen as a reproducible, clinically relevant model for evaluating the usefulness of FS. The FS consisted of pooled human fibrinogen (60 mg/mL) and thrombin (500 NIH U/mL). Time to hemostasis was measured, and adverse events were monitored. MethodsConsenting adult patients (n = 48) undergoing placement of a standard PTFE graft were randomized in a 2:1:1 ratio to the treatment group using FS (ZLB Bioplasma AG, Bern, Switzerland), oxidized regenerated cellulose (Surgicel, Johnson & Johnson, New Brunswick, NJ), or pressure. Patients received heparin (3,000 IU IVP) before placement of vascular clamps. If the treatment was FS, clamps were left in place for 120 seconds after the application of study material to permit polymerization. If treatment was Surgicel, clamps were left in place until the agent had been applied according to manufacturer’s instructions. If the treatment was pressure, clamps were released as soon as the investigator was ready to apply compression. Immediately after release of the last clamp, the arterial and venous suture lines were evaluated for bleeding. The time to hemostasis at both the venous and arterial sites was recorded. ResultsSignificant (P ≤ .005) reduction in time to hemostasis was achieved in the FS group. Thirteen (54.2%) patients randomized to FS experienced immediate hemostasis at both suture lines following clamp removal compared to no patients using Surgicel or pressure. Only one patient (7.1%) in the Surgicel group and no patients in the pressure group experienced hemostasis at 120 seconds from clamp removal, compared to 13 (54.2%) patients for FS. Adverse events were comparable in all groups. There were no seroconversions. ConclusionsFS achieved more rapid hemostasis than traditional techniques in this peripheral vascular procedure. FS use appeared to be safe for this procedure.

Experimental acute pancreatitis: the changes in pancreatic oxygen consumption and the effect of Dextran 40.

A canine model was devised to measure the oxygen consumption of the pancreas in experimentally induced pancreatitis. Over the 120 minute investigation period the oxygen consumption fell by 63% in the presence of a diminishing pancreatic blood flow and constant arteriovenous percentage saturation across the pancreas. Dextran 40 has been previously shown to maintain the pancreatic circulation. Accordingly a second group of dogs was treated with Dextran 40 (1.5 ml/kg) 60 minutes after induction of the pancreatitis. This produced a significant increase in the pancreatic oxygen consumption and widening of the arteriovenous difference. Dextran 40 appears to reverse the hypoxia of the pancreas noted in acute experimental pancreatitis.

A prospective randomized study comparing fibrin sealant to manual compression for the treatment of anastomotic suture-hole bleeding in expanded polytetrafluoroethylene grafts

OBJECTIVE The ideal hemostatic agent for treatment of suture-line bleeding at vascular anastomoses has not yet been established. This study evaluated whether the use of a fibrin sealant containing 500 IU/mL thrombin and synthetic aprotinin (FS; marketed in the United States under the name TISSEEL) is beneficial for treatment of challenging suture-line bleeding at vascular anastomoses of expanded polytetrafluoroethylene (ePTFE) grafts, including those further complicated by concomitant antiplatelet therapies. METHODS Over a 1-year period ending in 2010, ePTFE graft prostheses, including arterio-arterial bypasses and arteriovenous shunts, were placed in 140 patients who experienced suture-line bleeding that required treatment after completion of anastomotic suturing. Across 24 US study sites, 70 patients were randomized and treated with FS and 70 with manual compression (control). The primary end point was the proportion of patients who achieved hemostasis at the study suture line at 4 minutes after start of application of FS or positioning of surgical gauze pads onto the study suture line. RESULTS There was a statistically significant difference in the comparison of hemostasis rates at the study suture line at 4 minutes between FS (62.9%) and control (31.4%) patients (P < .0001), which was the primary end point. Similarly, hemostasis rates in the subgroup of patients on antiplatelet therapies were 64.7% (FS group) and 28.2% (control group). When analyzed by bleeding severity, the hemostatic advantage of FS over control at 4 minutes was similar (27.8% absolute improvement for moderate bleeding vs 32.8% for severe bleeding). Logistic regression analysis (accounting for gender, age, intervention type, bleeding severity, blood pressure, heparin coating of ePTFE graft, and antiplatelet therapies) found a statistically significant treatment effect in the odds ratio (OR) of meeting the primary end point between treatment groups (OR, 6.73; P < .0001), as well as statistically significant effects for intervention type (OR, 0.25; P = .0055) and bleeding severity (OR, 2.59; P = .0209). The safety profile of FS was excellent as indicated by the lack of any related serious adverse events. CONCLUSIONS The findings from this phase 3 study confirmed that FS is safe and its efficacy is superior to manual compression for hemostasis in patients with peripheral vascular ePTFE grafts. The data also suggest that FS promotes hemostasis independently of the patients own coagulation system, as shown in a representative population of patients with vascular disease under single- or dual-antiplatelet therapies.

Hepatic blood flow measurement. A comparison of the indocyanine green and electromagnetic techniques normal and abnormal flow states in the dog.

: Very few studies have compared the total hepatic blood flow using the Indocyanine green (ICG) method with the instantaneous electromagnetic flow method under unsteady circulatory conditions. In this study, a hypotensive circulatory state was produced by rapid hemorrhage in 14 dogs. Total hepatic blood flow was measured using the ICG single injection method, comparing it with the electromagnetic flow method. After confirming the validity of the ICG single injection method in measuring total hepatic blood flow in the steady state, the experiment was then carried out using 23 normal healthy dogs. The close correlation between the ICG clearance technique and the electromagnetic values under normal steady state was confirmed. However, after hemorrhage the indirect ICG method estimated only 71% of the simultaneous electromagnetic flow value. It is reasonable to assume that while the electromagnetic method continues to measure the actual total hepatic blood flow in both the steady and unsteady states, the ICG clearance method measures only the functional hepatic blood flow which is reduced due to shunting or impaired hepatocellular function in the unsteady and hypotensive circulatory state.

Hepatic blood flow measurement III. Total hepatic blood flow measured by ICG clearance and electromagnetic flowmeters in a canine septic shock model.

The validity of the ICG clearance method for the measurement of THBF in abnormal circulatory states remains questionable. In this study THBF measured by this method is compared with the electromagnetic flow technique in a canine septic model. Good correlation is demonstrated between the two in normal control animals. However, in the septic animals the ICG underestimated the electromagnetic flow result by 20%. This is true in both the high and the low cardiac output septic shock pictures that emerge. In the septic animals, the total hepatic blood flow as measured by the ICG was almost equal to the portal vein flow alone measured by the electromagnetic flowmeters suggesting that this was the quantity it was measuring in this abnormal state. Pathophysiologic mechanisms that may explain the discrepancy are given.

Management of Subclavian Arterial Injuries following Inadvertent Arterial Puncture during Central Venous Catheter Placement

Subclavian artery injuries after central venous catheter placement constitute a rare but potentially fatal complication. In this case series, the authors describe several endovascular treatment options in the management of iatrogenic subclavian arterial injuries resulting from inadvertent arterial placement of central catheters.

Utility of percutaneous intervention in the management of tunneled hemodialysis catheters.

A variety of interventional techniques have been developed to restore function to dysfunctional tunneled hemodialysis catheters (THC). The relative efficacies of these techniques were evaluated retrospectively to determine which therapy might be most beneficial. The records of malfunctioning THCs referred to interventional radiology between November 1995 and December 1999 were retrospectively reviewed. Dysfunctional THCs were studied using DSA images obtained while injecting contrast through the lumens of the THCs. The interventions performed were categorized into 1 of 5 groups: no treatment or conservative measures such as vigorous flushing; advancing a guidewire through the THC to reposition the catheter tip or to dislodge a small thrombus; catheter exchange over a guidewire; fibrin stripping of the THC using a loop snare; or prolonged (4 or more hr) direct thrombolytic infusion. A Cox Proportional Hazards model was developed to compare the rate of failure among the procedures. There were 340 THC studies. The catheters were managed as follows: 93 patients received conservative management only, 15 had a guidewire advanced through the catheter, 147 underwent catheter exchange, 62 were treated with a fibrin stripping procedure, and 23 received a thrombolytic infusion. Estimated 30-day patency rates for THCs were 38.2% for conservative management, 30.9% for guidewire manipulation of catheter tip, 53.6% for catheter exchange, 76.1% for fibrin stripping, and 69.8% for thrombolytic infusion. Differences among the treatments were observed (p < 0.01) and pairwise comparisons were made among the treatment groups. Failure rates were significantly higher in the catheter exchange (p <0.01) and guidewire manipulation at catheter tip (p <0.01) groups when compared with the fibrin stripping group. The catheter exchange and guidewire manipulation groups also experienced higher rates of failure when compared with the thrombolytic infusion group, although the differences were not statistically significant (p = 0.08, p = 0.17, respectively). Four procedure-related complications requiring hospitalization or other intervention occurred. Three of these were in the catheter exchange group with one incidence of sepsis, one drug reaction, and one hematoma. Fibrin stripping and thrombolytic infusion provided the greatest efficacy in the treatment of poorly functioning THCs, but all therapies demonstrated wide-ranging results. Central line exchanges did not provide a superior secondary patency and experienced more complications.

Hypertension of aortic coarctation: the role of renal and other factors.

In order to establish the relationship between the renal and other factors associated with the hypertension of coarctation of the aorta, aortic strictures were created in two groups of adult dogs (Groups A and B). Group B in addition had transference of total renal blood flow proximal to the stricture to eliminate the renal aspects of the hypertension. Carotid and femoral artery pressures were measured at monthly intervals for 24 weeks. Group A developed progressive generalised hypertension while Group B only developed hypertension proximal to the coarctation. The dominant role of a renal factor producing a generalised vascular response is confirmed, the localised proximal hypertension in Group B reflecting the mechanical obstruction imposed by the aortic stricture. There is no evidence to suggest that other organs distal to the coarctation are implicated in the development of arterial hypertension.

Mechanical Pleurodesis Aided by Peritoneal Drainage: Procedure for Hepatic Hydrothorax

BACKGROUND Hepatic hydrothorax in the setting of decompensated cirrhosis is a challenging and common clinical problem. Traditional therapies such as diuretics and transjugular intrahepatic portosystemic shunts can be effective therapies in selected patients but in patients ineligible for, or intolerant of, these traditional therapies, few effective therapeutic options remain for the management of hepatic hydrothorax. METHODS We present a series of 5 consecutive patients with refractory hepatic hydrothorax who underwent combined thorascopically guided mechanical and chemical pleurodesis aided by an intraperitoneal drain that prevented reaccumulation of the ascites while pleural inflammation and adhesion were progressing. We speculate that the prolonged contact between the parietal and visceral pleura allowed by prevention of reaccumulation of intraabdominal ascites and subsequent flux through the pleural space enhanced the efficacy of this procedure in comparison with those presented in the literature. RESULTS Despite the fact that all of our patients presented with decompensated cirrhosis, the surgical procedure and subsequent hospitalization were tolerated well by our entire cohort. Colonization of the pleural and peritoneal drainage fluid was a common complication of this procedure but was not associated with prolonged morbidity or mortality. CONCLUSIONS We present a therapy for the difficult clinical problem of refractory hepatic hydrothorax that may allow selected patients an opportunity for prolonged symptomatic control.

Differentiating pancreatic pseudocyst and pancreatic necrosis using computerized tomography.

Ten per cent of patients with acute pancreatitis will develop pancreatic complications. Differentiating pancreatic pseudocyst formation from pancreatic necrosis may be difficult based on clinical grounds. The purpose of this study was to evaluate the role of computerized tomography in differentiating these processes. A retrospective analysis was performed of 40 patients who developed pancreatic complications following an episode of acute pancreatitis and who subsequently underwent operation for drainage of their pancreatic fluid collections. All 40 patients had abdominal CT scans performed before surgery and the patients were then categorized on the basis of CT findings as having (1) a pseudocyst with a well-defined cyst wall, (2) peripancreatic fluid marked by the absence of a cyst wall, and (3) a combination of a pseudocyst as well as free peripancreatic fluid. Patients with pseudocysts had an average hospital stay of 14 +/- 2 days, a hospital morbidity rate of 16%, and a hospital mortality rate of 0%. In contrast, patients with peripancreatic fluid collections had an average hospital stay of 43 +/- 4 days (p less than 0.01) and hospital morbidity and mortality rates of 74% (p less than 0.01) and 22% (p less than 0.05), respectively. Patients with both pseudocysts and peripancreatic fluid collections behaved in a similar fashion to patients with peripancreatic fluid alone as characterized by a prolonged hospital stay and a high incidence (80%) of postoperative complications. At one year follow-up, 89% of the patients with pseudocysts were asymptomatic, whereas only 13% (p less than 0.01) of patients with peripancreatic fluid were symptom free. These data demonstrate that pseudocyst and peripancreatic fluid collections have markedly different biologic characteristics both in their short-term and long-term behavior. The results suggest that CT scanning can differentiate these processes and may help in directing the appropriate surgical therapy.