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Reducing Pain in Venipuncture
Author: Sheri Knepel, MD, Assistant Professor of Emergency Medicine, The Ohio State University, Columbus, OH.
Peer Reviewer: Moira Davenport, MD, Assistant Professor of Emergency Medicine, Allegheny General Hospital, Drexel University College of Medicine, Pittsburgh, PA.
In 2002, 28.6 million intravenous (IV) catheters were placed in U.S. emergency departments (EDs).1 Venous cannulation for IV starts and blood draws is the most common procedure in the acute care setting, and cannulation causes moderate to severe pain in a significant number of patients.2
Multiple guidelines from national and international organizations, including the American Academy of Pediatrics, the American Pain Society, and the Society of Infusion Nurses, have been issued for minimizing the predictable pain of IV initiation. However, a survey of U.S. EDs showed that few institutions have practice protocols for decreasing the pain of cannulation.3
This article reviews recent literature on a variety of approaches to decreasing the pain associated with IV cannulation in both adult and pediatric patients.
Topical Skin Coolant for IV Insertion in Adults: No Pain Relief
Source: Harstein BH, et al. Mitigation of pain during intravenous catheter placement using topical skin coolant in the emergency department. Emerg Med J 2008;25:257-261.
The authors of this study sought to evaluate if cryoanesthesia, the use of a topical coolant to reduce pain, was an alternative to cutaneous analgesia for IV cannulation in an ED setting. The proposed mechanism for this type of anesthesia is that the rapid evaporation of the agent cools the skin and temporarily disrupts interpretation of pain signals.
The study was an unblinded, randomized, controlled study of a convenience sample of adults at two tertiary care centers. They used a skin coolant (1,1,1,3,3-pentafluropropate and 1,1,1,2-tetrafluoroethane) applied for 2-4 seconds and immediately followed by IV insertion. The outcome evaluated was decrease in pain of IV cannulation, and secondary outcomes were patient anxiety and projection of future anxiety, patient's pain during skin preparation, staff evaluation of vein visualization, and staff perception of the effect of the spray on procedural success. Outcomes were all evaluated via questionnaire responses.
The study found that the mean pain scores, using a 100 mm Visual Analogue Scale (VAS), were 27 mm (95% CI 19.9-34.1) in the study group and 28 mm (95% CI 20.4-35.6) (p=0.934) in the control group. There was no statistically significant difference between the two groups. Pain of preparation was slightly increased, anxiety regarding future IV cannulation attempts was less, and vein visualization was slightly improved in the study group. Sixty-eight percent of staff said they would use the spray again, and 72% of study participants reported that they would choose the spray prior to future cannulation attempts.
Cryoanesthesia is typically easy to use, cost effective, and instantaneous in effect, potentially making it an ideal method for decreasing the pain of IV cannulation in an acute care setting. Unfortunately, evaluation of this method, which has been studied many times, has yielded mixed results. In this study, there is no statistical significance in pain reduction. Interestingly, however, both the patient and operator would opt to use this method for future cannulations.
Topical Skin Coolant for IV Insertion in Children: Pain Relief
Source: Farion KJ, et al. The effect of vasocoolant spray on pain due to intravenous cannulation in children. CMAJ 2008;179:31-36.
In this study, farion and colleagues evaluated the effectiveness of a vasocoolant spray to decrease the pain of IV cannulation in children.
This was a randomized, placebo-controlled, double-blind trial in 80 children age 6-12 years who were receiving IV cannulation at an academic tertiary children's hospital. A skin coolant (1,1,1,3,3-pentafluropropate and 1,1,1,2-tetrafluoroethane) was sprayed for 4-10 seconds, until skin blanching occurred; that was followed by cannulation within 60 seconds. Primary outcome was patient-reported pain. Secondary outcomes were success rate on first attempt and rating of patient's pain by parents, nurses, and child life specialists (who were present and provided distraction at every IV attempt).
This study found a significant reduction in patient-reported pain on a 100 mm VAS in the study group versus the control group (mean difference 19 mm, 95% CI 6-32 mm; p< 0.01). Evaluation of pain by parents, nurses, and child life specialists was significantly decreased with the study group, as well. Additionally, cannulation on the first attempt was 85% in the study group versus 62% in the control group, making the number needed to treat to prevent cannulation failure five.
In this study, the same vasocoolant spray was used to evaluate effect on pain during IV cannulation in children as was used in the previous study with adults. Interestingly, the results of these two studies were very different. This study showed a clinically significant decrease in pain as perceived by the patient, parents, nurses, and child life specialists.
This yields the questions: What was the difference between the two studies? Was it the difference in technique used (a 2- to 4-second application in the first study versus a 4- to 10-second application until skin blanching was achieved in the second study)? Was it the change in patient population? Or was there another variable that caused the difference in the study results?
Overall Pain Relief from Topical Skin Coolant During IV Cannulation
Source: Hijazi R, et al. Effect of topical alkane vapocoolant spray on pain with intravenous cannulation in patients in emergency departments: Randomised double blind placebo controlled trial. BMJ 2009;338;b215.
This is another recent study in which the authors evaluated the effectiveness of a topical vasocoolant spray prior to IV cannulation in decreasing the pain of the procedure.
This was a randomized, double-blind, placebo-controlled trial in 201 adults at a teaching hospital in Melbourne, Australia. In the study group, a vasocoolant spray (a combination of propane, butane, and pentane) was sprayed for two seconds followed by IV cannulation within 15 seconds. The primary outcome was measurement of pain with cannulation. The secondary outcomes evaluated included discomfort with skin preparation, success rate with first IV attempt, preference for spray use for future cannulations, and skin irritation at five days.
The results showed a significant reduction in pain with IV insertion in the study group (12 mm, 95% CI 5-40) versus the control group (36 mm, 95% CI 19-51) (p<0.001). Additionally, no significant pain with skin preparation was noted, and a significant number of study participants would choose the spray for future IV insertions. Cannulation success rate was increased in the study group, but the result was not significant. Two patients reported transient erythema at the site, but no persistent effects were noted.
In this third study using a different vasocoolant in an adult population, a statistically significant reduction in pain was found in the study group. Additionally, participants again would prefer the intervention for future IV insertions.
At this point, no study yet definitively answers if this intervention provides clinically significant pain decrease in all patient populations. However, this well done study does add weight to the pro argument.
Warm Topical Patches and Pain Relief During IV Insertion
Source: Singer AJ, et al. Warm lidocaine/ tetracaine patches versus placebo before pediatric intravenous cannulation: A randomized controlled trial. Ann Emerg Med 2008;52:41-47.
Singer and colleagues compared a topical lidocaine/tetracaine patch versus placebo for reducing the pain of IV cannulation in a pediatric ED. The patch evaluated was a transdermal patch that included an oxygen-activated heating pod with a eutectic mix of lidocaine and tetracaine that has been FDA-approved for dermal anesthesia over intact skin.
This was a randomized, controlled, double-blind trial in 45 patients age 3-17 years who presented to a pediatric ED and required non-emergent IV insertion. A lidocaine/tetracaine patch or an identical placebo patch was placed while in triage for patients in whom the need for IV placement was anticipated. The patch was placed at least 20 minutes prior to cannulation. After cannulation, the patient's pain was measured on a 100 mm VAS or on the Wong Baker Faces scale. Secondary outcomes included cannulation success, parent assessment of adequate anesthesia, parental preference for future use of the patch, nursing assessment of pain, and presence of adverse events.
The median pain of IV cannulation in the active treatment group (18 mm) was significantly lower than in the placebo group (35 mm) (p=0.04). The number of successful IV cannulations was similar. Parent assessment of adequate pain relief was more common in the study group (75%) versus the control group (35%). Additionally, nursing satisfaction was higher with the intervention group and more parents would request it for future use, but these results were not statistically significant. The number of adverse events was similar.
This study showed moderate success in decreasing the pain of IV cannulation in a relatively small patient population with the lidocaine/tetracaine patch versus placebo. The heating element, which expedites absorption and decreases the pretreatment time to 20 minutes, makes it a reasonable pre-intervention treatment option in the acute care setting for non-emergent patients, especially if placed in the triage setting. An advantage to the patch is that it is similar in appearance to an adhesive bandage and may be more easily accepted and less anxiety-provoking for children than some other interventions. Interestingly, although not statistically significant, a greater number of parents would request the patch again for future cannulations. A larger study with increased power would be helpful in evaluating the benefits of this product and the significance of the secondary outcomes.
Laser-assisted Topical Anesthesia and IV Insertion Pain
Source: Singer AJ, et al. Laser-assisted anesthesia prior to intravenous cannulation in volunteers: A randomized, controlled trial. Acad Emerg Med 2005;12: 804-807.
Absorption of topical anesthesia is limited by the stratum corneum, the outer layer of the epidermis. In this study, the authors hypothesized that removing a 6 mm diameter area of this layer with a single pulse of a lightweight, portable, FDA-approved erbium:yttrium-aluminum-garnet (Er:YAG) laser would lead to enhanced uptake of a topical numbing agent and decrease the pain of IV cannulation.
This was a randomized, controlled, double-blind clinical trial in 30 healthy adult volunteers. One hand in each subject was treated with the laser and the other hand with a sham laser. Topical lidocaine (4%) cream was then applied for five minutes bilaterally, and an IV was placed. Primary outcomes were pain of skin preparation and pain of IV cannulation. Secondary outcomes were success of IV cannulation and the presence of a burn, infection, or scarring at one week and three months.
The mean pain of cannulation after laser-assisted topical anesthesia was significantly less than after sham laser treatment (13 mm, 95% CI = 8-19 versus 29 mm, 95% CI 22-36). No significant erythema or scarring occurred, and cannulation was successful in all attempts. Of note, 80% of subjects would prefer laser treatment prior to future IV cannulation.
This study is an inventive approach to expediting the time for topical anesthetic to be effective. The cost is moderately prohibitive at $2,000/laser and an additional $6/application (versus $0.20 for an application of vasocoolant spray), and logistics may be difficult in an acute care setting. At this time, the technology may better serve a non-acute care setting, but the concept has potential.
Does Jet-injected Anesthesia Provide Pain Relief During IV Insertion in Children?
Source: Zempsky WT, et al. Needle-free powder lidocaine delivery system provides rapid effective analgesia for venipuncture or cannulation pain in children: Randomized, double-blind, comparison of venipuncture and venous cannulation pain after fast-onset needle-free powder lidocaine or placebo treatment trial. Pediatrics 2008;121:979-987.
This study evaluates the use of a novel, needle-free, powdered lidocaine delivery system versus a sham placebo to provide analgesia for pediatric vein cannulation. The active device is a sterile, single-use, pre-filled, disposable system that uses pressurized helium gas in a microcylinder to deliver lidocaine powder at a velocity significant enough to penetrate the epidermis and to allow for rapid absorption and anesthesia. The sham placebo device looked and sounded the same without delivering a pressurized dose of anesthetic. The goal of the study was to determine if effective local analgesia could be achieved in 1-3 minutes for venipuncture and peripheral IV procedures in children with this device.
This was a randomized, double-blind, sham-placebo-controlled phase 3 study of the device. The study was called COMFORT-003 (Comparison of Venipuncture and Venous Cannulation Pain After Fast Onset Powdered Lidocaine or Placebo Treatment). Five hundred seventy-nine patients age 3-18 years were randomly enrolled in six hospitals to receive lidocaine via the needle-free system or the sham placebo 1-3 minutes prior to cannulation. The authors measured patient pain (via the Wong-Baker Faces scale and on a 100 mm VAS), parent's perception, and safety of the device.
Results revealed mean Wong-Baker Faces scores of 1.77 versus 2.1 in the study versus the control groups, which reflected a statistically significant decrease in pain (p=0.11). Parental assessments of the child's pain were also lower and side effects were transient and mild (primarily erythema and petechiae).
This was a large phase 3 trial done over six hospital systems. The results indicated that this device has the potential to provide safe, well-tolerated, rapid administration of topical anesthesia which decreased pain perception by the patients and parents. The cost of the device was not discussed, and it could potentially be prohibitive for mass use to mitigate pain with cannulation. There was also potential for bias in the study, which was sponsored by the manufacturer. However, this device does have potential applications in the acute care setting.
Jet-injected Anesthesia vs. Placebo for IV Insertion in Children
Source: Auerbach M, et al. A randomized, double-blinded controlled study of jet lidocaine compared to jet placebo for pain relief in children undergoing needle insertion in the emergency department. Acad Emerg Med 2009;16:388-393.
The objective of this study by Auerbach and colleagues was to determine if needle-less, jet-delivered lidocaine decreased the pain of needle insertion in children. The system evaluated was a low-cost ($2/dose), FDA-approved device that uses pressurized carbon dioxide gas to deliver buffered 1% lidocaine or placebo (normal saline) at a velocity great enough to penetrate the epidermis.
This was a randomized, placebo-controlled, double-blind study of 150 children age 5-18 years undergoing needle insertion. A separate, non-concurrent phase of the study was an unblinded, non-intervention control group of 47 patients to evaluate any inherent placebo effect of the jet device. Treatment was delivered 60 seconds prior to cannulation. Patients reported pain on a 100 mm Color Analogue Scale (CAS). Operators reported their ability to visualize the vein. Both patients and operators reported satisfaction with the device.
The mean pain score was statistically similar between the jet lidocaine and jet placebo groups (28 mm versus 34 mm) (p=0.2277). Both were statistically lower than the no-intervention group (52 mm) (p<0.05). The majority of patients receiving the jet device would request it in the future. Providers did not report a change in visibility or patient cooperation between the two groups.
Interestingly, this study found that there was a decrease in pain with jet injection of lidocaine or jet injection placebo versus no intervention, but it did not find that jet injection of lidocaine was superior to jet injection of placebo. The results differ from the results in the previously discussed study.
In this study, there was active jet-injection of the placebo device instead of a placebo device that looked and sounded like the active device without delivering pressure. This elicits the question of whether the outcome is due to the placebo effect or if the mechanism is the delivery of pressure to the area, causing a transient attenuation of pain signals. Another study of just the device with normal saline versus sham placebo would help elicit the answer. Demonstrated again, patients in the intervention group would request it for future cannulations.
Nitrous Oxide for Pain Relief During IV Insertion in Children
Source: Furuya A, et al. The effective time and concentration of nitrous oxide to reduce venipuncture pain in children. J Clin Anesth 2009;21:190-193.
Nitrous oxide has rapid onset and both analgesic and mild sedative effects. This study was designed to investigate the time of administration and the optimal concentration of inhaled nitrous oxide needed to decrease the pain associated with IV cannulation.
This was a prospective, randomized study conducted in a pediatric operating room prior to IV start for general anesthesia. Seventy-three patients age 6-15 years presenting for elective surgery were randomly assigned to one of the following four groups:
Group 1 - 50% N2O in O2 for three minutes;
Group 2 - 50% N2O in O2 for five minutes;
Group 3 - 70% N2O in O2 for three minutes;
Group 4 - 70% N2O in O2 for five minutes.
After N2O administration, an IV was established. Patient pain was assessed using the revised Bieri face scale by a parent and by a nurse. Pain scores from parents in Groups 3 and 4 were significantly lower than in Groups 1 and 2. Pain scores from nursing in Group 3 were lower than in Group 1. Parental and nursing scores did not differ between Groups 3 and 4. Additionally, there were no episodes of bradycardia or hypoxia in any participant. Side effects of tearing, excitement, and crying developed in seven of the 73 patients. Frequency of side effects was similar among all four groups.
The authors concluded that inhalation of 70% nitrous oxide for three minutes prior to IV cannulation was effective in decreasing pain.
This is a practice that may not be ready for prime time in most acute care settings. However, it offers an interesting concept for EDs currently with N2O sedation capabilities.
This study supports the use of 70% N2O in O2 for three minutes prior to venous cannulation versus other protocols of N2O in O2 sedation in the pediatric population. However, 70% N2O is frequently associated with side-effects of excitement, restless movements, and nausea or vomiting in children. Nearly 10% of patients in this study experienced side effects. This seems to be a fairly high incidence when other alternatives may offer equivalent relief in pain and anxiety with a lower side-effect profile. There is also the question of how the risk/benefit and side effect profile would translate into an adult population.
Jet-injection of Lidocaine vs. Topical Anesthesia for IV Pain in Children
Source: Spanos S, et al. Jet injection of 1% buffered lidocaine versus topical Ela-Max for anesthesia before peripheral intravenous catheterization in children. Pediatr Emerg Care 2008;24:511-515.
Spanos and colleagues compared J-tip needle-free jet injection of 1% lidocaine to a 30 minute application of 4% Ela-Max for anesthesia prior to insertion of a peripheral IV.
This study was a prospective, randomized, controlled trial in 70 children age 8-15 years presenting to a pediatric ED. The primary outcome was patient's pain. Subjects rated their pain on a VAS, and the procedure was videotaped and reviewed by a single-blinded reviewer for observer reported VAS pain score. Secondary outcomes evaluated included pain of the injection, anxiety, nursing satisfaction, and success rates of IV placement.
Patient reported pain was significantly reduced in the jet-injection group (17.3 versus 44.6, p<0.001). Blinded reviewer VAS scores trended lower in the jet injection group, as well, but the result was not statistically significant. Difference in anxiety was not different between the two groups, and there was no significant difference in nursing satisfaction or success rates, although trends favored jet-injection.
This study is unique in that it compares the standard method of decreasing the pain of pediatric peripheral IV insertions, topical cream, to the jet injection. Results favored jet injection of lidocaine with a significant decrease in patient reported procedural pain. Additionally, a blinded observer rated pain. Interestingly, this decrease in pain was not as significant as patient reported decrease, which brings into question the possible placebo effect of the jet injection changing perception of the pain experienced. Regardless, this is perhaps worth consideration at $2.10/dose.
Lidocaine: Better than Vasocoolant and N2O for Pain Relief in IV Insertion in Adults
Source: Robinson PA, et al. Lignocaine is a better analgesic than either ethyl chloride or nitrous oxide for peripheral intravenous cannulation. Emerg Med Australas 2007;19:427-432.
This study compared three different methods for reducing pain prior to peripheral IV insertion. Robinson and colleagues compared intradermal lidocaine, ethyl chloride topical vasocoolant spray, and inhaled 50% N2O in O2.
The study was a randomized, controlled trial of 300 subjects older than 15 years at a large tertiary care center in New Zealand with four study groups:
No anesthesia and immediate cannulation;
One-minute inhalation of 50% N2O;
Ethyl chloride spray for 5-10 seconds prior to cannulation;
0.1 mL of 1% lidocaine injected prior to cannulation.
Patients rated their pain on a 100 mm VAS immediately after cannulation. Patients with no intervention reported the most pain (VAS 20 mm, 95% CI 15-25), and those who received the 1% lidocaine injection reported the least pain (VAS 1 mm, 95% CI 0-6) (P< 0.001). Cannulation success was not effected. Pain with N2O and ethyl chloride spray was less than with no intervention, but it was not statistically significant.
This study was ambitious in that it directly compared three methods of anesthesia prior to IV cannulation. Two questions come to light: First, were the optimum application of N2O and topical vasocoolant spray chosen? Second, which method provided the greatest patient satisfaction? Of note, was the pain of lidocaine insignificant, or did the pain of injection negate the decrease in pain of cannulation in patients' rating of satisfaction? Despite the limitations, it does reiterate that some intervention is better than none.
Lidocaine: Better than Topical Cream for Pain Relief in IV Insertion in Adults
Source: McNaughton C, et al. A randomized, crossover comparison of injected buffered lidocaine, lidocaine cream, and no analgesia for peripheral intravenous cannula insertion. Ann Emerg Med 2009;54:214-220.
Mcnaughton and colleagues chose to directly compare the pain and anxiety of peripheral IV insertion with no anesthesia, topical 4% lidocaine, or intradermal 1% buffered lidocaine in a group of health care providers who acted as their own controls.
This was a randomized, unblinded, crossover design study in which three peripheral IVs were inserted into 70 medical students and nurses at IV workshops. After each insertion, pain, anxiety, and preference for future use on self and as a provider were rated on a 10-point scale.
Median pain scores were 7 with no local anesthesia, 3 with topical cream, and 1 with injected 1% lidocaine. Anxiety scores were 4 without anesthesia and 2 with anesthesia. Seventy percent of subjects reported they would request buffered lidocaine prior to peripheral IV insertions.
This study is interesting for two reasons. First, it directly compares topical and subcutaneous lidocaine. Second, it compares the use of them on providers. Results favored the injection of buffered 1% lidocaine, and 70% of the providers stated they would request it on themselves in the future. Of note, use of either numbing technique significantly reduced anxiety. Additionally, after participating in this study, the providers stated the experience would influence their future practice.
The ideal approach to decreasing the pain of cannulation would have the following characteristics: high efficacy, convenient and easy to use, rapid onset, low cost, needle free, good safety profile, with no complex or special equipment and no detrimental effect on procedural success. At this time, a variety of approaches exist, but none has all of the desirable characteristics.
First, there is the topical vasocoolant. This is cheap and easy with a rapid onset and a good safety profile. Unfortunately, there are mixed results in multiple studies, some of which were reviewed in this article, in regards to efficacy.
Next, there are topical numbing agents. They are relatively inexpensive and effective, with good ease of use and a low side-effect profile. The main downside to these products is the time to onset. Due to the need for the product to cross the outer layer of the epidermis, average time to effect is about 45 minutes if there is no intervention. One intervention reviewed was the topical warming patch, which decreased time to effectiveness to 20 minutes. This has definite potential but may still take too long for application in the acute care setting. Another approach has been to remove a very small portion of the stratum corneum, as was done in the laser study. This was effective but costly, and it may be worth revisiting as technology advances.
Finally, there is injected lidocaine. This is cheap and probably the most effective. When injected with a needle, there is associated pain, anxiety, and increased potential for needle sticks. A new approach has been to use a jet injection system to avoid the extra needle stick. This, too, has yielded mixed results. Interestingly, the pressure of the jet injector itself causes some pain relief even without lidocaine. This could lead to interesting future explorations.
At this time, it does not seem that there is yet a perfect answer to the problem of providing anesthesia for peripheral cannulation. It is worth noting two things: First, patients prefer something to nothing, even if the intervention caused no significant decrease in pain. Second, in head-to-head trials with vasocoolant, topical creams, and N2O, 1 mL of injected buffered 1% lidocaine provided the greatest pain relief and was preferred by patients.
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3. Bhargava R, et al. Procedural pain management patterns in academic pediatric emergency departments. Acad Emerg Med 2007;14:479-482.