Effect of cold application and compression on pain and bruising in subcutaneous heparin injection

Background and AimSubcutaneous administration may result in complications such as bruising and pain at the injection site. This study was performed as in order to determine the effect of cold application and compression on pain and bruising in subcutaneous heparin injection.MethodsThe study was a randomized controlled trial. 72 patients were included in the study. Each patient in the sample was both experimental (cold and compression) and control groups and 3 different parts of abdomen were used for injection of each patient. The data of the research were collected by using Patient Identification Form, Subcutaneous Heparin Observation Form and Visual Analog Scale (VAS).ResultsIn the study, it was observed that after heparin injection, ecchymosis developed in 16.4%, 28.8%, and 54.8% of the patients, respectively, and pain was experienced during injection in 12.3%, 43.5%, and 44.2% of the patients, respectively, on the pressure, cold application, and control site groups, and this difference was statistically significant (p<0.001).ConclusionIn the study, it was found that bruising size of the compression group was smaller in contrast with the other groups. When the VAS mean was examined for the groups, it was found that the patients in the compression group had lower pain than the other groups. In order to prevent complications that may arise in nurses' subcutaneous heparin injections and to increase the quality of patient care, it may be recommended to transfer the 60-second compression application after subcutaneous heparin applications to clinical applications and to conduct studies comparing compression and cold application with other applications for future studies.     

A Phase I Study to Assess the Effect of Speed of Injection on Pain,Tolerability, and Pharmacokinetics After High-volume Subcutaneous Administration of Gantenerumab in Healthy Volunteers

PurposeGantenerumab, a fully human anti–amyloid-β IgG1 monoclonal antibody that binds to aggregated forms of amyloid-β, is being investigated as a potential disease-modifying treatment for early (prodromal to mild) Alzheimer disease (AD). Our study compared the pain associated with 5- and 15-s subcutaneous injections of gantenerumab and evaluated the tolerability and pharmacokinetic properties of subcutaneous gantenerumab.MethodsThis randomized, open-label, single-active-dose, placebo-controlled crossover study was conducted in 50 healthy volunteers aged 40–80 years with no history of clinically significant disorders, drug or alcohol abuse, familial history of early-onset AD, or prior gantenerumab exposure. Eligible participants were randomized to a sequence of one 300-mg SC gantenerumab injection into the abdomen and 2 SC placebo injections (1 into the abdomen and 1 into the thigh) during 5 or 15 s. All injections were administered at least 90 min apart. Participants were assessed for local pain by visual analog scale (VAS) and verbal rating scale; safety profiles were assessed by recording adverse events (AEs), and plasma pharmacokinetic properties were also evaluated.FindingsImmediately after the subcutaneous gantenerumab injection, the pain VAS score was numerically higher without reaching statistical significance in the 5-s versus 15-s injection group (VAS least-squares mean difference, 7.492 mm; 95% CI, −4.439–19.423 mm). In both injection speed groups, the mean pain VAS score was comparable after subcutaneous gantenerumab and placebo injections into the abdomen. Pain was reported after needle insertion and immediately after dosing, subsiding within 5 min after the dose. The pain VAS score was numerically higher after SC placebo injection into the thigh versus abdomen (5-s injection group: mean [SD] VAS score, 26.68 [27.83] vs 19.20 [25.60] mm; 15-s injection group: mean [SD] VAS score, 14.16 [20.62] vs 9.48 [12.04] mm). No serious AEs were reported; no participants withdrew because of an AE. All AEs were of mild intensity, were transient, and had resolved without sequelae at follow-up. The most common AEs were injection site reactions; redness was the most frequently observed skin reactivity event after subcutaneous gantenerumab administration (5-s injection group: 36%; 15-s injection group: 32%). After subcutaneous administration, gantenerumab reached a peak plasma concentration at a median time of 119 h (approximately 5 days); plasma concentrations declined in a monoexponential manner. Comparable pharmacokinetic profiles were observed between the injection speed groups.ImplicationsSubcutaneous gantenerumab injections at speeds of 5 and 15 s were well tolerated in healthy volunteers and could enable at-home administration by patients with AD or their caregivers. ClinicalTrials.gov identifier: NCT02882009.     

An experimental study on the use of manual pressure to reduce pain in intramuscular injections

To investigate whether the application of manual pressure to the injection site before intramuscular injection reduces pain. An experimental study with intrasubject comparison was conducted using manual pressure to reduce pain associated with intramuscular injection. Seventy-four subjects, participating in an immunization vaccination campaign, were recruited by convenience sampling from a university. They were required to receive two doses of vaccines via intramuscular injections. One was given in a conventional way, i.e. without manual pressure being applied prior to the injection (control condition). The other was given with manual pressure being applied prior to the injection (experimental condition) for 10 seconds. The two conditions were randomly allocated for each subject. The instrument for measuring the perceived pain intensity was the Pain Intensity Verbal Rating Scale (Cantonese). To ensure the consistency of manual pressure being applied to the injection site, a mechanical pressure sensor device was used to record the manual pressure being applied. The mean manual pressure applied was 190.82 mmHg (SD=5.25). Results demonstrated a significant difference in the perceived pain intensity for experimental and control conditions. Subjects with manual pressure applied before injections reported lower pain intensity scores, whilst those without the application of manual pressure before injections reported higher pain intensity scores. Applying manual pressure to an injection site before performing an injection could be an effective means of decreasing pain intensity.     

Using Buzzy,Shotblocker, and Bubble Blowing in a Pediatric Emergency Department to Reduce the Pain and Fear Caused by Intramuscular Injection: A Randomized Controlled Trial

IntroductionProcedural pain in general, and intramuscular (IM) injection pain in particular, is one of the most distressing and painful health care experiences for children. Pharmacologic and nonpharmacologic methods are used as forms of pain control for children undergoing acute painful interventions in emergency departments.MethodsThis study was a prospective, randomized controlled trial. The sample consisted of children aged 5 to 10 years old who required IM injections. Children were placed in 4 subgroups through randomization, using a computer program: the Buzzy (MMJ Labs. Atlanta, GA) group (n = 40), the ShotBlocker (Bionix Development Corporation, Toledo, OH) group (n = 40), the bubble-blowing group (n = 40), and the control group (n = 40). Immediately before and after the injection, the children, their parents, and an observer were asked to evaluate the child’s level of fear. The Oucher scale was also employed by the observers, children, and parents immediately after the procedure to assess the level of pain in the children in each group.ResultsNo statistically significant difference was determined between the control and intervention groups in terms gender, age, previous pain experienced with injection, the parent who was with the child, the parent’s age. A significant difference was found between the intervention and control groups in terms of levels of pain and fear during IM injection. Pain and fear were notably less in the group of children receiving the Buzzy intervention.DiscussionThe Buzzy intervention should be used when children are undergoing IM injections to reduce their levels of pain and fear.     

Effect of the Buzzy Application on Pain and Injection Satisfaction in Adult Patients Receiving Intramuscular Injections

AimThe aim of this study was to investigate the effect of the Buzzy application on pain and satisfaction during injections.BackgroundIntramuscular injections usually cause some degree of pain at the injection site. Patients are often afraid of receiving injections because they perceive that it will be painful.DesignThe study was a single-blind, randomized controlled trial.MethodPatients (n = 65) who receive diclofenac sodium intramuscularly at a state hospital in a city in the western region of Turkey were included in the study. The study data were collected by The Patient Information Form and Visual Analog Scale (VAS). Pain intensity and injection satisfaction scores were evaluated using the VAS.ResultsAccording to the findings of this research, the post-injection pain intensity and injection satisfaction scores of patients in the application group were found to be higher than in the control group.ConclusionIn conclusion, the Buzzy device has the potential to reduce injection related pain in adult patients who may be fearful of receiving such injections.     

A New Approach on the pain management of intramuscular injection: A Triple-Blind Randomized Clinical Trial

BackgroundPain management is an important part of care provided by nurses.AimsThe present study aimed to investigate the effect of an innovative method named the skin traction, pressure, and rapid muscle release (TPR) on reducing IM injection pain compared with the Z-track injection methodDesignThis triple-blind clinical trial investigated 63 patients who required Methocarbamol injection.MethodsTwo, 5-cc methocarbamol injections were given to each patient by the two techniques in two of his/her muscles. In the TPR technique, after applying skin traction and imposing deep pressure on the muscle, the needle was inserted at a 90° angle near the skin and the muscle was released rapidly towards the needle. Hence, the needle was embedded in the muscle. However, muscle release was not applied in the Z-track method. The visual analog scale (VAS) was used to measure pain intensity. For data analysis, T-independent and χ² tests were used.ResultsThe findings showed that the mean pain score in TPR and Z-track methods was 1.68 ± 1.20 and 3.76 ± 1.42, respectively. The difference was statistically significant.ConclusionThe results of this study showed that the innovative method (TPR) can be used as a substitute for the Z-track method to reduce IM injection pain.     

Effects of applying external cold and vibration to children during vaccination on pain,fear and anxiety

ObjectivesThis study aimed to evaluate the effectiveness of the application of external cold and vibration on children experiencing pain, fear and anxiety during vaccination.Design and settingThis randomized controlled, experimental study was conducted in primary schools selected within the scope of school immunization days by a community health center. The study population consisted of first grade students who were scheduled to receive a booster dose of diphtheria, tetanus, and acellular pertussis, inactivated poliovirus vaccine (DTaP-IPV) vaccine within the scope of the school immunization program of the said community health center and the study sample consisted of 90 students (experimental: 45, control:45).Main outcome measuresIn the experimental group, a device that applies external cold and vibration (Buzzy®) was placed on the injection site for 30 s before administration of the vaccine. The device was then placed above the injection site and kept there during the injection. No intervention was made during the injections in children included in the control group. The same nurse administered the injections in the experimental and control groups.ResultsIn the current study, it was found that there was a statistically significant difference between the experimental group and the control group in terms of the children’s pain, the nurse’s pain, the nurse’s fear and the children’s anxiety (p < 0.05), but no statistically significant difference in terms of the children’s fear (p > 0.05). Conclusions: It was concluded that applying external cold and vibration during vaccination has an effect on the level of children’s pain and anxiety.     

Evaluation of the Pharmacokinetic Profile of Ultra Rapid Lispro Administered Subcutaneously at Different Injection Sites

PurposeUltra rapid lispro (URLi) is a novel insulin lispro formulation developed to more closely match physiological insulin secretion and improve postprandial glucose control. This study compared the pharmacokinetic profile and glucodynamic response of URLi when administered subcutaneously into the abdomen, upper arm, or thigh. An intravenous (IV) bolus administration was included to determine the absolute bioavailability at each injection site.MethodsIn this Phase I, randomized, open-label, 4-period, crossover study, healthy subjects received a single dose of 15 U URLi subcutaneously into the abdomen, upper arm, or thigh, or by intravenous injection. Serum insulin lispro concentrations and glucodynamic response during a 10-hour euglycemic clamp procedure were assessed after URLi administration.FindingsTotal insulin lispro exposure was similar for the abdomen, upper arm, and thigh, and absolute bioavailability was ～65% at each subcutaneous (SC) injection site. Total and peak insulin action were similar across these SC injection sites. The onset of appearance was <1 minute, and the time to early half-maximal drug concentration occurred at ～10 minutes across these three SC injection sites. Onset of insulin action occurred at ～22 minutes, and the early insulin action (for the first hour) was also similar across these SC injection sites. URLi was well tolerated after single SC injections and IV bolus administration.ImplicationsThe pharmacokinetic and glucodynamic profiles of URLi were similar after a single SC dose into the abdomen, upper arm, or thigh. The rate of insulin lispro absorption and early insulin action were maintained regardless of the SC injection site. The current study supports SC injection of URLi into the abdomen, upper arm, and thigh. ClinicalTrials.gov identifier: NCT03232983.     

The Effıcacy of External Cooling and Vibration on Decreasing the Pain of Local Anesthesia Injections During Dental Treatment in Children: A Randomized Controlled Study

PurposeThis study was performed to assess the efficacy of external cooling and vibration devices on the pain of injections applied to the site of local anesthesia in children during dental treatment.DesignThis study is a randomized controlled trial.MethodsThis study was conducted with 60 children requiring mandibular baby teeth extraction. The children in the experimental group were anesthetized after cold application, and a vibration device was administered on the application site 2 minutes before and during the anesthesia process, whereas those in the control group were only given local mandibular anesthesia without any other procedure.FindingsIt was found that the mean pain score was lower in the experimental group with a significant difference between the groups (P < .05).ConclusionsThis study found that the application of external cooling and vibration on the site of local anesthesia had a significant effect on the injection pain experienced by children during dental treatment.     

Ultrasound-Guided Standard vs Dual-Target Subacromial Corticosteroid Injections for Shoulder Impingement Syndrome: A Randomized Controlled Trial

ObjectiveTo compare dual-target injection with standard ultrasound (US)-guided subacromial injection in patients with subacromial impingement syndrome (SIS) and possible disorders of the biceps long-head tendons.DesignDouble-blind, randomized controlled trial.SettingRehabilitation outpatient clinic.ParticipantsPatients with SIS (N=60).Intervention(1) US-guided standard subacromial bursa; (2) dual-target (subacromial bursa plus proximal biceps long-head tendon) injection, with 40-mg triamcinolone acetonide administered to patients in each group.Main Outcome MeasuresClinical assessments were performed at baseline. The outcomes, including results from a self-administered questionnaire, the Shoulder Pain and Disability Index (SPADI), and a self-pain report, the visual analog scale (VAS) scores for pain at rest, at night, and during overhead activities, were evaluated at baseline and at the first and third months postintervention.ResultsNo significant difference was observed in baseline evaluations between groups (n=30 in each treatment arm) prior to injections. Both groups exhibited significant SPADI and VAS-score improvements after the first month. The dual-target injection group had less rebounding pain at the 3-month follow-up. The standard injection group had more patients reporting worsening pain within 1 day postinjection.ConclusionUS-guided dual-target corticosteroid injection showed similar short-term efficacy to standard subacromial injections, but with an extended duration of symptom relief. Therefore, dual-target corticosteroid injections may be useful for shoulder pain treatment in patients with SIS.     

A study on the effect of the duration of subcutaneous heparin injection on bruising and pain

Aim. This study was carried out to determine the effect of injection duration on bruising and pain following the administration of the subcutaneous injection of heparin. Background. Although different methods to prevent bruising and pain following the subcutaneous injection of heparin have been widely studied and described, the effect of injection duration on the occurrence of bruising and pain is little documented. Design. This study was designed as within‐subject, quasi‐experimental research. Method. The sample for the study consisted of 50 patients to whom subcutaneous heparin was administered. Heparin was injected over 10 seconds on the right abdominal site and 30 seconds on the left abdominal site. Injections areas were assessed for the presence of bruising at 48 and 72 hours after each injection. Dimensions of the bruising on the heparin applied areas were measured using transparent millimetric measuring paper. The visual analog scale (VAS) was used to measure pain intensity and a stop‐watch was used to time the pain period. Data were analysed using chi‐square test, Mann–Whitney U, Wilcoxon signed ranks tests and correlation. Results. The percentage of bruising occurrence was 64% with the injection of 10 seconds duration and 42% in the 30‐second injection. It was determined that the size of the bruising was smaller in the 30‐second injection. Pain intensity and pain period were statistically significantly lower for the 30‐second injection than for the 10‐second injection. Conclusions. It was determined that injection duration had an effect on bruising and pain following the subcutaneous administration of heparin. This study should be repeated on a larger sample. Relevance to clinical practice. When administering subcutaneous heparin injections, it is important to extend the duration of the injection.     

Interleukin-6 induces spatially dependent whole-body hypersensitivity in rats: implications for extracephalic hypersensitivity in migraine

BackgroundMigraine is a complex neurological disorder that is characterized by throbbing head pain, increased sensitivity to light, sound, and touch, as well as nausea and fatigue. It is one of the most common and most disabling disorders globally but mechanisms causing migraine are poorly understood. While head pain is a typical feature of attacks, they also often present with cutaneous hypersensitivity in the rest of the body. In contrast, primary pain conditions in the lower parts of the body are less commonly associated with cephalic hypersensitivity. Previous studies indicate that application of stimuli to the meninges of rodents causes cutaneous facial as well as hindpaw hypersensitivity. In the present study, we asked whether widespread hypersensitivity is a unique feature of dural stimulation or whether body-wide responses occur similarly when the same stimulus is given in other locations.MethodsRats were given the same dose of IL-6 either via dural, intraplantar, subcutaneous, intramuscular, intracisternal, or intrathecal injection. Cutaneous facial and hindpaw allodynia was assessed using Von Frey following injection into each location.ResultsHindpaw allodynia was observed following dural and intraplantar injection of IL-6 in both males and females. Hindpaw allodynia was only observed in females following intracisternal and intrathecal IL-6 injections. In contrast, facial allodynia was only observed in either sex following dural and intracisternal injections, which would activate meningeal afferents and the trigeminal nucleus caudalis (TNC), respectively.ConclusionsHere we show that while stimulation of upper body regions with IL-6 including the meninges and brainstem can cause widespread hypersensitivity spreading to the paws, similar stimulation of the lower body does not cause the spread of hypersensitivity into the head. These data are consistent with the observations that whole body hypersensitivity is specific to conditions such as migraine where pain is present in the head and they may provide insight into co-morbid pain states associated with migraine.     

Tezepelumab Pharmacokinetics,Safety, and Tolerability After Administration via Vial-and-syringe,Accessorized Prefilled Syringe,or Autoinjector: A Randomized Trial in Healthy Volunteers

PurposeTezepelumab is an anti–thymic stromal lymphopoietin monoclonal antibody therapeutic in development for patients with severe, uncontrolled asthma. In ongoing Phase III studies, tezepelumab is administered via subcutaneous (SC) injections using a vial-and-syringe (V–S). This study compared the pharmacokinetic (PK) parameters, safety, and tolerability of tezepelumab administered subcutaneously via V–S versus via an accessorized prefilled syringe (APFS) or autoinjector (AI).MethodsThis single-center, randomized, open-label, parallel-group study was conducted in healthy volunteers aged 18–65 years. Participants, stratified according to weight (50 to <70 kg, 70 to <80 kg, or 80–90 kg), were randomized evenly to 9 groups representing injections to the abdomen, thigh, or upper arm via V–S, APFS, or AI. Tezepelumab PK parameters over 113 days were evaluated after a single 210-mg SC dose. The primary end points were comparison of C_max and AUC_0–∞ between device groups. Further PK parameters, immunogenicity, safety (including injection site reactions [ISRs] and injection site pain [visual analog scale]) were also assessed.FindingsA total of 315 adults were randomized to treatment. Geometric mean ratios for comparisons between device groups of C_max, AUC_0–∞, and AUC_0–last were close to 1, with 90% CIs all within the range of 0.8–1.25, meeting bioequivalence criteria. PK variables were also similar between devices across injection sites and weight categories. Across devices, thigh injection resulted in slightly higher exposure than upper arm injection, and abdomen injection resulted in exposure similar to or slightly lower than thigh injection; however, these differences were not clinically meaningful. Treatment-emergent anti-tezepelumab antibodies were present in 3 (2.9%), 1 (1.0%), and 0 participants in the V–S, APFS, and AI groups, respectively. Treatment-related adverse events were reported in 15.0% of participants overall (V–S, 10.7%; APFS, 18.1%; AI, 16.0%), including ISRs in 1 (1.0%), 3 (2.9%), and 3 (2.8%) participants in the V–S, APFS, and AI groups. Median visual analog scale pain score (0–100 mm scale) was 2 mm immediately after injection and was 0 mm at 30 min for all groups.ImplicationsTezepelumab PK parameters after a single 210-mg SC dose were comparable when administered via V–S, APFS, or AI. In all groups, immunogenicity rate and injection site pain were low, and ISRs were uncommon. These findings support administration of tezepelumab via APFS or AI, in addition to V–S, providing patients and physicians with greater choice and the potential convenience of at-home use. ClinicalTrials.gov identifier: NCT03989544.     

Number of botulinum toxin injections needed to stop requests for treatment for chronic lateral epicondylar tendinopathy. A 1-year follow-up study

BackgroundEpicondylar tendinopathy (“tennis elbow”) is a serious issue in manual labourers. Symptoms can persist over months or even more than 1 year, even when treated with trinitrine patches, acupuncture, sclerosis of neovessels, shock-wave therapy, autologous blood injections, platelet-rich plasma or hyaluronic acid. Botulinum toxin (BoNT-A) injections showed promising short-term results, but the long-term beneficial effects are not yet known.ObjectiveWe aimed to assess the long-term effect, side effects and recurrence rate after BoNT-A injections on chronic lateral epicondylar tendinopathy during 1 year.MethodsThis open study followed a 3-month randomized controlled trial. We included 50 patients followed at day 0 (V0), 90 (V1), 180–270 (V2) and 365 (V3). The main judgment criterion was the number of BoNT-A injections required to achieve pain relief with no further request for treatment by the patient.ResultsAfter one BoNT-A injection, 22/50 (44%) patients did not ask for further treatment during follow-up because of complete pain relief, and 20/50 (40%) asked for a second BoNT-A injection. For 20 patients with a second injection, 18 (90%) did not ask for further treatment during follow-up. Only 1 patient had a recurrence of pain after an initial pain relief of greater than 75%. Quality of life, and painful and maximal gripping force improved significantly at V1, V2 and V3 as compared with V0, and repercussions on daily and professional activities decreased significantly (P < 0.05).ConclusionsOne or 2 BoNT-A injections has favourable results for chronic epicondylar tendinopathy.     

Pilot Study of Human Recombinant Hyaluronidase–Enhanced Subcutaneous Hydration and Opioid Administration for Sickle Cell Disease Acute Pain Episodes

ABSTRACT

The objective of this study was to determine the feasibility of protocol-driven human recombinant hyaluronidase (rHuPH20)-enhanced subcutaneous (SC) hydration and opioid administration in adults presenting to the emergency department (ED) with sickle cell disease acute pain episodes (SCDAPE). Adults with SCDAPE were given 150 U of rHuPH20 and normal saline subcutaneously. Opioids were administered SC every 15 minutes for 4 hours until numerical rating scale (NRS) pain intensity scores fell to <5, or Ramsay Sedation Scores were >4. Pain intensity and pain relief were recorded hourly. Total morphine equivalents and fluid volume, total pain relief (TOTPAR), patient- and physician-perceived global efficacy, patient-perceived global SC needle discomfort, physician-rated ease of needle placement, and adverse effects were noted. Ten patients (6 males, 4 females), mean age 32.9 years (23–56 years) completed the trial. Mean pain intensity scores fell 25% (from 9.2 to 6.9) from baseline and mean 4-hour TOTPAR score was 4 (maximum: 16). A mean total of 119 mg (70–170 mg) morphine equivalents and 846 mL (200–1650 mL) normal saline were administered. Mean patient and physician global perceived efficacy ratings were 3.4 and 4.2 (of 5). Patient global discomfort of SC needle presence was 2.7 (of 10), and ease of needle placement was physician rated at 4 (of 4; easiest). Patients experienced mild swelling and stinging at the SC site, and no infusion required discontinuation. The authors conclude that rHuPH20-enhanced subcutaneous hydration and opioid administration appear feasible from this pilot study. These results need confirmation in a controlled clinical trial.     

Clinical evaluation of large volume subcutaneous injection tissue effects,pain, and acceptability in healthy adults

Determining feasibility and tolerability of large volume viscous subcutaneous injection may enable optimized, intuitive delivery system design. A translational early feasibility clinical study examined large volume subcutaneous injection viability, tolerability, acceptability, tissue effects and depot location for ~1, 8, and 20 cP injections at volumes up to 10 ml in the abdomen and 5 ml in the thigh in 32 healthy adult subjects. A commercial syringe pump system delivered 192 randomized, constant rate (20 µl/s) injections (6/subject) with in‐line injection pressure captured versus time. Deposition location was qualified via ultrasound. Tissue effects and pain tolerability were monitored through 2 hours post‐injection with corresponding Likert acceptability questionnaires administered through 72 hours. All injection conditions were feasible and well‐tolerated with ≥79.3% favorable subject responses for injection site appearance and sensation immediately post‐injection, increasing to ≥96.8% at 24 hours. Mean subject pain measured via 100 mm visual analog scale increased at needle insertion (6.9 mm, SD 10.8), peaked during injection (26.9 mm, SD 21.7) and diminished within 10 minutes post‐removal (1.9 mm, SD 4.2). Immediate injection site wheal (90.9%) and erythema (92.6%) formation was observed with progressive although incomplete resolution through 2 hours (44.6% and 11.4% remaining, respectively). Wheal resolution occurred more rapidly at lower viscosities. Most subjects (64.5%) had no preference between abdomen and thigh. Correlations between tissue effects, injection pressure and pain were weak (Pearson’s rho ± 0–0.4). The large volume injections tested, 1–20 cP viscosities up to 10 ml in the abdomen and 5 ml in the thigh, are feasible with good subject acceptability and rapid resolution of tissue effects and pain.

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

Traditional chronic disease intravenous therapy is transitioning to subcutaneous administration, creating viscous formulations delivered at volumes exceeding the traditional threshold of 1.5–3.0 ml. Understanding the local physiological impact and corresponding tolerability of large volume subcutaneous injection is key to optimized, intuitive delivery system design.

• WHAT QUESTION DID THIS STUDY ADDRESS?

Early feasibility clinical to determine feasibility and tolerability of constant rate (20 µl/s), 1–20 cP, 5–10 ml subcutaneous placebo injections to the thigh and abdomen in healthy adults. Are injections and corresponding local tissue effects visible, acceptable, and quick to resolve?

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

Localized tissue effects (wheals and erythema) and pain are common but transient with broad, favorable acceptability for subcutaneous injections up to 10 ml and 20 cP. Pain peaks during injection, returning to pre‐injection levels within 30 minutes. Tissue effects are larger and slower to resolve for thigh and/ or higher volume and viscosity injections.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

The tolerability and feasibility boundaries of large volume subcutaneous administration include and likely exceed the injection conditions tested.     

The Acute Effects of Manual and Instrument-Assisted Cervical Spine Manipulation on Pressure Pain Threshold,Pressure Pain Perception,and Muscle-Related Variables in Asymptomatic Subjects: A Randomized Controlled Trial

ObjectiveThe purpose of this study was to compare the immediate effects in asymptomatic participants of manual and instrument-assisted cervical manipulation on pressure pain thresholds, pressure pain perception, and muscle mechanical properties (tone, stiffness, and elasticity) over muscles anatomically related and unrelated to the manipulated level.MethodsFifty-nine asymptomatic participants (34 women and 25 men; age [mean ± standard deviation] = 21.1 ± 1.6 years) were randomly assigned to 4 groups in a double-blind, randomized, placebo-controlled trial. Two groups received cervical (C3/C4) manipulation, 1 manual and the other instrument-assisted; the third group received a sham manipulation; and the fourth group served as the control. Bilateral pressure pain threshold, pressure pain perception, muscle tone, stiffness, and elasticity in the upper trapezius and biceps brachii were evaluated before and immediately after the interventions.ResultsAt baseline, there were no differences among the groups on any variable. After the interventions, a significant increase in pressure pain threshold was observed with both manual and instrument-assisted manipulation at local and distal sites (P < .05), whereas no changes were observed in either the control or the placebo group. The perception of pain pressure did not change significantly in any group. The interventions did not promote any statistically significant differences in muscle tone, elasticity, or stiffness at any site (local or distal).ConclusionCervical (C3/C4) manual and instrument-assisted manipulations produced an increase in pressure pain threshold bilaterally and over muscles related and unrelated to the vertebral segment, but had no effect on muscle tone, elasticity, or stiffness.     

Pharmacokinetics of apomorphine in parkinsonian patients

Summary— Apomorphine, a dopamine agonist, has been used efficiently in parkinsonian patients to treat severe levodopa-induced on-off phenomenon. Motor improvement has been obtained both with continuous subcutaneous (SC) infusions, and multiple SC injections. So as to assist in the understanding of the clinical results, we studied the peripheral pharmacokinetics of apomorphine in 20 patients after intravenous (IV) or SC injections in the anterior abdominal wall and in the thigh at various doses, or SC infusion. Plasma apomorphine levels were measured by high-performance liquid chromatography with electrochemical detection. After an SC injection in the abdominal wall, the T_max was brief (16 ± 11 min) the drug was rapidly cleared from the plasma and had a short plasma half-life (69.7 ± 25.8 min). The AUC was similar following SC and IV injections, suggesting that apomorphine was completely absorbed from subcutaneous tissue. Inter-subject variability in drug absorption was large. We noticed a trend towards a more complete absorption following injection in the abdominal wall rather than in the thigh. In patients chronically treated by continuous SC infusion, the apparent plasma half-life was five times longer than that following SC or IV injections. These pharmacokinetic data may explain the rapid onset and brief duration of clinical effects, and the usefulness of individual titration for intermittent SC apomorphine injections, and the smoother motor response obtained with continuous SC infusions.     

Ventrogluteal versus dorsogluteal site selection: A cross-sectional study of muscle and subcutaneous fat thicknesses and an algorithm incorporating demographic and anthropometric data to predict injection outcome

BackgroundThe dorsogluteal and ventrogluteal intramuscular injection sites both have their use in clinical practice; however, it has not been established in whom one or the other should be preferentially targeted or avoided. There is a need for an evidence-based approach towards site selection for a successful intramuscular injection outcome and to avoid unwanted injection outcomes of inadvertent subcutaneous injection or bone contact. Injection outcome is dependent on injection site subcutaneous fat thickness and muscle thickness; these are likely influenced by gender and anthropometry.ObjectivesTo determine whether subcutaneous fat, muscle, and total tissue thicknesses differ between the dorsogluteal and ventrogluteal sites, and whether theoretical injection outcome (intramuscular, subcutaneous, or bone contact) can be predicted by demographic and anthropometric data and described by an algorithm.DesignCross-sectional study design.SettingsUniversity in Australia.Participants145 volunteers (57% female) of at least 18 years of age recruited through the university community.MethodsAnthropometric data was collected and subcutaneous fat and muscle thicknesses were quantified by ultrasonography. Anthropometric differences between theoretical injection outcome groups (bone contact versus intramuscular versus subcutaneous at the ventrogluteal and dorsogluteal sites) was determined for each gender (ANOVA). Multiple regression analysis was conducted to determine the influence of demographic and anthropometric data on theoretical intramuscular injection outcome. An algorithm to guide site selection was developed for each gender, based on the anthropometric measures that best discriminated between injection outcomes.ResultsSubcutaneous fat, muscle and total tissue were significantly thicker at the dorsogluteal site than the ventrogluteal site, and subcutaneous fat was significantly thicker in females than males at both sites (all p < 0.001); there was no gender difference for muscle or total tissue thickness at either site. Female gender, and waist and hip circumference were significant predictors of subcutaneous fat thickness at both sites; male gender was a significant predictor of dorsogluteal site muscle thickness (all p < 0.05). In the algorithm developed for site selection based on theoretical injection outcome, the best discriminators were: weight, BMI and waist circumference for females, and weight and distance between the iliac tubercle and anterior superior iliac spine for males.ConclusionsThe algorithm describes when each of the ventrogluteal and dorsogluteal sites is appropriate or should be avoided, based on easily obtained anthropometric data. This has direct relevance in clinical practice in evidence-based site selection for gluteal intramuscular injections for optimal medication and health outcomes.     

Effect of Topical Anesthetic Cream on Pain During Periareolar Injection of Technetium Tc99m Sulfur Colloid for Sentinel Lymph Node Biopsy in Breast Cancer: A Randomized Control Trial

BackgroundInjection of Tc99m to localize nodes for sentinel lymph node biopsy is reported by patients as very painful. The purpose of this study was to determine if anesthetic cream reduces pain associated with periareolar injection of Tc99m and to help elucidate conflicting literature regarding the efficacy of anesthetic cream for this procedure.MethodsA randomized, double-blind, placebo-controlled methodology was used for adult females with breast cancer undergoing periareolar injection of Tc99m for sentinel lymph node biopsy. Pain levels were compared using anesthetic cream (2.5% lidocaine/2.5% prilocaine) vs. placebo. Patient exclusion criteria included use of opioids or adjuvant pain medication or injecting Tc99m the day before surgery. The Numerical Rating Scale was used to assess pain levels immediately after the injections.ResultsComparing 23 experimental and 26 control patients, there was no significant difference between the experimental (median = 4) and the control group (median = 5) on level of pain experienced U= 0.492, P > .05.ConclusionsThe experimental group had a slightly lower median pain score; however, there was no statistically significant difference between those who used the cream compared with those who used a placebo, supporting the conclusion that anesthetic cream does not reduce pain during Tc99m injections. This study adds to the current literature to provide a stronger position that there is no benefit to using anesthetic cream for this procedure.