To determine whether heparinized saline would be more effective in maintaining the patency of peripheral IV catheters in dogs compared to 0.9% sodium chloride.
To determine whether heparinized saline would be more effective in maintaining the patency of peripheral IV catheters in dogs compared to 0.9% sodium chloride.
Prospective blinded randomized study.
University Veterinary Teaching Hospital.
Thirty healthy purpose bred dogs, intended for use in the junior surgery laboratory, were utilized. The dogs were randomized into 1 of 3 groups, 2 treatment groups and a control group.
An 18-Ga cephalic catheter was placed in the cephalic vein of each dog. Each dog in the treatment group had their catheter flushed with either 10 IU/mL heparinized saline or 0.9% sodium chloride every 6 hours for 42 hours. The dogs in the control group did not have their catheters flushed until the end of the study period. Immediately prior to flushing catheters, each catheter was evaluated for patency by aspiration of blood and the catheter site was evaluated for phlebitis.
All dogs in the heparinized saline and 0.9% sodium chloride group had catheters that flushed easily at each evaluation point. More dogs in the saline group had catheters from which blood could not be aspirated, but there was no significant difference between these groups. All dogs in the control group had catheters that flushed easily at the end of the assigned 6 hour interval except in 1 dog. Phlebitis was not detected in any dog.
Flushes of 0.9% sodium chloride were found to be as effective as 10 IU/mL heparinized saline flushes in maintaining patency of 18-Ga peripheral venous catheters in dogs for up to 42 hours. For peripheral catheters placed with the intention of performing serial blood draws, heparinized flushes may be warranted.
Peripheral IV catheters are indispensable lifesaving tools commonly used in hospitalized human and veterinary patients to administer fluids, medications, and parenteral nutrition.[1-7] Medical personnel in the ICU work to ensure that these devices remain patent during the patient's stay in the hospital. Loss of IV catheter patency may lead to compromised patient care, increased costs associated with replacing the catheters, and increased patient discomfort.[3, 8, 9]
Occlusion and catheter site phlebitis are 2 common complications associated with peripheral IV catheters in human and veterinary patients.[10, 11] Catheter occlusion is thought to occur due to factors such as catheter site infection, duration of catheterization, or patient-related risk factors. Those factors ultimately lead to thrombus formation. A great deal of work has been devoted to develop different catheter materials that minimize activation of coagulation. Catheter clot formation has also traditionally been addressed by filling and flushing catheters with solutions with anticoagulant properties such as heparin, citrate, and vitamin C. In human patients, complications associated with the use of heparin in flush solutions include drug interactions, heparin-induced thrombocytopenia, bleeding complications, thrombosis syndrome, and allergic reactions.[15-18] Many studies in human patients have shown that the use of heparinized saline does not provide any additional benefit over the use of 0.9% sodium chloride flushes in peripheral catheters,[8, 9, 19-22] although a few studies show that heparin may have a protective effect against catheter clot formation.[14, 23] These studies have led many human hospitals to discontinue the use of heparin in peripheral catheter flushes.[8, 9] To the authors’ knowledge, there are no veterinary studies comparing the efficacy of heparinized saline and 0.9% sodium chloride flush. While there are no known reports of heparin-induced thrombocytopenia in veterinary patients, there is still a risk of allergic reactions, drug interactions, and bleeding complications (eg, inadvertent heparinization).[24, 25]
The purpose of this study was to determine whether heparinized saline is more effective than 0.9% sodium chloride in maintaining the patency of peripheral IV catheters in dogs. We hypothesized that heparinized saline (10 IU/mL) would be more effective in maintaining peripheral catheter patency than catheters flushed with 0.9% sodium chloride.
The present study was a prospective, randomized, double-blinded controlled study. The study protocol was approved by the Institutional Animal Use and Care Committee at Auburn University. Healthy purpose bred dogs intended for use in the junior surgery laboratories at the authors’ institution were utilized in this study. All dogs received a physical examination at the beginning of the study and were deemed to be healthy based on their physical examination findings.
An 18-Ga, 1.25-inch over-the-needle polyurethane catheter1 was percutaneously placed in the right cephalic vein at the distal third of the antebrachium. If the catheter was unsuccessfully placed in the right cephalic vein, the left cephalic vein was utilized. All catheter sites were shaved and the area was aseptically prepared using iodine and alcohol scrubs before the catheters were placed. All catheter sites were prepared in an identical manner. The catheters were capped with an infusion plug2 and secured with medical adhesive tape. A transparent sterile dressing3 was incorporated in the securement to allow for catheter site visualization. Immediately after placement all catheters were assessed for patency by syringe aspiration of at least 0.1 mL of blood and easy injection of 3.0 mL 0.9% sodium chloride.4 An assistant holding the dog palpated along the cephalic vein to confirm free flow of the flush solution, while also observing for SC extravasation of the flush solution. An Elizabethan collar was placed on each dog after catheter securement, and the dogs were constantly monitored directly by an individual to ensure the catheters were not inadvertently removed.
The study subjects were randomized into 1 of 3 groups: a heparinized saline group5 (HS), a nonheparinized 0.9% sodium chloride group (S), and a control group that received no flush except that performed immediately after catheter placement and after the final evaluation (C). The control group was used to help determine how long after placement thrombosis of the catheter was likely to occur when left unflushed. Thirty dogs were enrolled in the present study. Twenty-four dogs were randomized to the HS (n = 12) and S (n = 12) groups. Six dogs were randomized in the C group: 2 in the C12 group, 2 in the C24 group, and 2 in the C42 hour group. The 12-hour control group (C12) had catheters aspirated and then flushed with 0.9% sodium chloride 12 hours after the catheters were placed. The 24-hour control group (C24) had catheters aspirated and flushed with 0.9% sodium chloride 24 hours after the catheters were placed, and the 42-hour control group (C42) had catheters aspirated and then flushed with 0.9% sodium chloride 42 hours after the catheters were placed. The catheters were removed from the subjects in the C group after a single attempt to withdraw blood and flush them with 0.9% sodium chloride.
All catheter evaluations were evaluated by 1 of 2 investigators (YU or AO). Every dog had its catheter site evaluated for evidence of phlebitis and patency every 6 hours. Phlebitis was defined as the presence of any of the following: erythema, tenderness, swelling, unusual discharge or warmth. A rectal temperature was also taken from each dog during each evaluation. Catheter patency was evaluated by the ability to aspirate at least 0.1 mL of blood (while the cephalic vein was occluded proximal to the catheter) with little resistance. The aspiration was done prior to the administration of the flush solution. Patency was also evaluated by the ability to administer 3 mL of flush solution without resistance or SC extravasation through the catheter. All catheters in the S and HS groups were evaluated for patency in the same manner.
All catheter flushes were performed by 1 of 2 investigators (YU or AO). The study solutions were prepared by 1 of the investigators who was blinded to the treatment groups. Each syringe of study solution was labeled with a predetermined study code to ensure blinded randomization. The dogs in the HS and S groups had their catheters evaluated and flushed with 3 mL of 10 IU/mL heparinized saline and 3 mL of 0.9% sodium chloride, respectively, every 6 hours until the end of the study period. Once enrolled, the subjects continued to receive the same study solution throughout the duration of the study. Catheters were removed upon discovery of nonpatency or at the end of the study. In the HS and S groups, the subjects were followed for 42 hours from the time of catheter placement.
A sample size calculation was performed before the study to determine appropriate sample size. We calculated that 12 dogs would be sufficient to show the difference between the 2 groups at 80% power with an alpha < 0.05. Data were analyzed using commercial statistical software.6 A stratified 2×2 contingency table analysis and Fisher's exact test were used to evaluate the differences between the HS and S groups in regards to blood withdrawal from the catheters. The change in body temperature of the animals was analyzed using Student t-test. A value of P < 0.05 was considered significant.
The HS and S groups had 7 female and 5 male dogs each. The C group had 3 male and 3 female dogs. The average weight of the dogs was 13.6 kg (SD ± 3.45 kg) in the HS group, 16.8 kg (SD ± 5.50 kg) in the S group, 14.8 kg (SD ± 5.27 kg) in the C group.
All dogs in the HS and S groups had catheters that flushed easily at every time point of evaluation. All dogs in the C group had catheters that flushed easily at the end of the assigned 6 hour interval except 1 dog in the C42 group, whose catheter was deemed to be obstructed and would not flush with moderate pressure applied.
The proportion of catheters successfully aspirated in the HS and S groups at different time points is detailed in Table 1. Despite the difficulty in aspirating blood from multiple catheters in the S group, there was no statistically significant difference between the HS and S groups at each time point (Table 1). All dogs in the C group had blood aspirated from their catheters with minimal resistance except 1 dog in the C42 group. This was the same dog whose catheter would not flush at the end of the study period.
|0 h||6 h||12 h||18 h||24 h||30 h||36 h||42 h|
All catheters used in the study were placed during the first attempt to get venous access in the limb ultimately used for the study. There were technical difficulties associated with placing peripheral catheters in the right cephalic vein in 4 dogs (1 in the S group and 3 in the C groups). As a result, those catheters were placed in the left cephalic vein. In the HS group, the study was discontinued after 24 hours in 1 dog and after 36 hours in another dog because of inadvertent catheter removal by the dogs. In the S group, the study was discontinued after 30 hours and 36 hours in 2 dogs, respectively, due to inadvertent catheter removal by the dogs.
In both S and HS groups, no dog showed any signs of phlebitis at the catheter site. In the C group, 1 dog showed mild erythema in the C12 subgroup and 1 dog had extravasation of the flush solution in the C42 subgroup at the final evaluation. There were no statistically significant changes in temperature in the dogs in any group through the course of the study.
The use of heparin as an antithrombotic agent in catheters is common in both human and veterinary medicine.[1-3, 26-28] However, despite wide use, the benefit of heparinized flushes in veterinary patients has not been investigated. Previous investigations in human patients have suggested that intermittent flushing of IV catheters with nonheparinized saline is equally as effective in maintaining catheter patency without significant side effects.[8, 19-22, 29] In addition, many complications including thrombocytopenia and coagulopathy have been reported with prolonged administration of heparin in human patients.[9, 30-34] There have been reports describing serious complications and sometimes fatal outcomes in human patients with heparin complications.[31-33, 35] While there are no studies documenting heparin-induced thrombocytopenia in dogs and cats, this may be a potential risk in small animal patients. In the present study, no obvious complications associated with heparin administration, such as petechia and ecchymosis, were observed during the study period. However, there are potential benefits of replacing heparinized saline flush with nonheparinized flush. These benefits include elimination of risks associated with heparin and decreased potential for infection associated with loss of sterility of flush solution when the heparin flush is prepared, thereby providing safer therapy for the patient and substantial financial savings for the hospital.[9, 22, 36, 37]
The present study showed no statistically significant difference between the use of heparinized and nonheparinized flush in maintaining peripheral catheter patency for 42 hours (Table 1). The findings in the C group actually suggest that 18-Ga catheters can maintain their patency without any additional flushes for at least 24 hours after the catheters were placed and 1 of 2 catheters remained patent up to 42 hours. All catheters in both HS and S groups flushed easily during each evaluation point through the end of the study period. While there was no statistically significant difference noted between these 2 groups, there was a higher incidence of catheter failure in aspirating blood back from the S group than the HS group. However, all the catheters that failed on blood aspiration were able to be flushed easily. Furthermore, those catheters continued to be functional until the end of the study period. A possible explanation for lack of aspiration followed by ease of flushing is that there were small clots in the catheters that inhibited blood withdrawal and those clots were easily disrupted with the flush solution. It is also possible that factors other than coagulation, including inadequate pressure when holding off the cephalic vein, may have contributed to the failure of blood aspiration from the catheters. While it has been shown that peripheral catheters can be used to collect serial blood samples from dogs, withdrawing of blood from peripheral catheters is not a common veterinary clinical practice. Based on the results of this study, when peripheral catheters are intended for serial blood collection, a heparinized flush solution may be preferred to 0.9% sodium chloride.
The size of catheter (18-Ga) was chosen for this study to maximize the ease of blood aspiration. Fluid flow rates have been shown in dogs to increase exponentially with increased catheter radius. The large catheter size helped ensure optimal flow rate during aspiration. The same size catheter was used for all subjects to maintain uniformity. The effect of the catheter size on patency was not evaluated, but smaller catheters would be expected to be more susceptible to thrombosis.[40, 41] Additional studies are needed to evaluate if heparinized saline solutions will be more effective in maintaining patency of smaller diameter catheters in veterinary patients.
Polyurethane catheters were chosen for this study since previous studies have shown that polyurethane catheters permit longer patency with less risk for phlebitis than teflon catheters.[42, 43] Polyurethane catheters have smoother microsurface, are thermoplastic and more hydrophilic, and tend to be much more flexible than teflon. They also induce less platelet adherence in vitro and causes less thrombosis and inflammation in experimental animals. Silicone catheters may cause fewer local complications although conflicting evidence is available.[44, 45] It is possible that the use of a Teflon catheter material may have changed the results obtained in this study. Further studies evaluating the role of catheter material and thrombosis in veterinary patients should be considered.
The study period (42 h) was influenced by the availability of dogs. To the authors’ knowledge, there is no study describing the average indwelling period for peripheral catheters in veterinary medicine. Anecdotally, most catheters at the authors’ institution are in place for an average of 36 hours before they are inadvertently removed or become no longer needed. At many veterinary institutions, peripheral catheters are used almost immediately after placement for continuous infusion of IV fluids and are infrequently left unused. These catheters are usually not flushed until the continuous infusion of fluids is discontinued since we believe it is much less likely to be obstructed as long as the catheter is used for the continuous infusion. However, in the authors’ institution, obstructions are noted in these peripheral IV catheters while they are being used for the continuous infusion of fluid. This brings into question the role of heparinized flushes for catheters used for continuous infusions of fluids. Human studies evaluating the role of heparin in flushes have evaluated peripheral intermittent IV lines like evaluated in the current study.[19, 46] Peripheral intermittent infusion devices are capped IV catheters that are used to maintain fluid balance, deliver intermittent medication, and provide access for emergency treatment. They are not routinely used on a continuous basis and might have an increased tendency for venous obstructions than catheters used continuously. To the authors’ knowledge, no reports have described the efficacy and necessity of flushing catheters with continuous flow of fluids in human patients. More studies are warranted in veterinary medicine to evaluate the role of flushes in catheters with continuous flow of fluids.
Phlebitis is commonly associated with duration of catheter patency because inflammatory stimulation at the catheter site induces clot formation.[12, 14] The presence of phlebitis was determined based on the subjective findings of extravasation, erythema, pain, and swelling at the catheter site as well as rectal temperature elevation. Our study found no significant increase in the risk of phlebitis in heparinized or nonheparinized saline groups for up to 42 hours.
Only 1 concentration of heparinized saline (10 IU/mL) was used in this study. The differences in heparin concentrations in flush solutions on maintaining patency of peripheral IV catheters was not assessed. One study evaluating arterial catheters demonstrated that using 0.25 IU/mL of heparin was equally as effective as 1 IU/mL, but there are no known studies comparing heparin concentrations for use in peripheral IV catheters. Human studies evaluating the efficacy of heparin in flush solutions have used a wide range of heparin concentrations varying from 0.1 to 10 IU/mL.[40, 41, 47] We used 10 IU/mL of heparin in this study because we sought to maximize the effect of heparin and ultimately demonstrate a difference, if any, between the HS and S groups.
There are several limitations in the present study. The patency of the peripheral IV catheter was determined qualitatively by the investigator who flushed the catheter. Both investigators have had years of experience flushing IV catheters, but there was no objective measurement of catheter patency. The duration of the current experiment was limited to 42 hours, and peripheral catheters are often maintained for longer periods in clinical patients. Differences may exist between the HS and S flush groups if the study could be performed for a longer period. Future research utilizing a more objective measurement of peripheral IV catheter patency in a larger population for a longer duration of time is warranted. It would also be important to assess the effect of different catheter sizes and materials on the need for heparinized flushes.
In conclusion, nonheparinized 0.9% sodium chloride flushes were found to be as effective as 10 IU/mL heparinized saline flushes in maintaining patency of 18-Ga peripheral IV catheters in dogs for up to 42 hours. For peripheral catheters placed with the intention of performing serial blood draws, heparinized flushes may be warranted.
The authors would like to thank Kyle Owens BS, LVT and Brittany Scroggins for their assistance with the study.
Terumo Medical Corporation, Elkton, MD.
Hospira Inc., Lake Forest, IL.
3M Health Care, Neuss, Germany.
0.9% sodium chloride solution, Braum Medical Inc, Irvine, CA.
Heparin sodium injection, 1000 USP units/mL. APP Pharmaceuticals LLC, Schaumburg, IL.
Statistical Analysis System software, SAS release version 9.2, Cary, NC.