Allometric Scaling of Testosterone Enanthate Pharmacokinetics to Adolescent Hypogonadal Males (IM and SC Administration).

Context: Intramuscular (IM) testosterone enanthate (TE) and testosterone pellets were US Food and Drug Administration approved before 1962 for pediatric use but not studied in controlled trials in adolescents. Objective: An analysis using nonlinear mixed effect (NLME) modeling was designed to evaluate the adult pharmacokinetics (PK) of subcutaneous (SC) and IM TE. This model was used to simulate SC and IM TE administration in adolescents of different weight groups. Methods: Data from adult male patients in a phase 2 trial were used to characterize the PK of TE using population PK modeling for SC and IM administration: Allometry was used to scale PK parameters from the adult model to simulate adolescent (aged 12 to < 18 years) serum testosterone levels at body weights of 30, 40, 50, and 60 kg after weekly, every-other-week (EOW), and monthly SC and IM administration of 12.5, 25, 50, 75, and 100 mg TE regimens. Results: The final data set included 714 samples from 15 patients receiving 100 mg SC TE and 123 samples from 10 patients receiving 200 mg IM TE. In simulated populations, average serum concentration SC:IM ratios were 0.783, 0.776, and 0.757 at steady state for weekly, EOW, and monthly dosing groups, respectively. Simulated regimens of 12.5 mg SC TE monthly produced serum testosterone levels representative of early puberty and simulated pubertal stage progression following multiple subsequent testosterone dose increases. Conclusion: SC TE administration achieved a testosterone exposure-response relationship similar to IM TE in simulated adolescent hypogonadal males, which may reduce size of fluctuations in serum T and related symptoms.

A randomized comparison of loss of resistance versus loss of resistance plus electrical stimulation: effect on success of thoracic epidural placement.

BACKGROUND: Loss of resistance (LOR) for epidural catheter placement has been utilized for almost a century. LOR is a subjective endpoint associated with a high failure rate. Nerve stimulation (NS) has been described as an objective method for confirming placement of an epidural catheter. We hypothesized that the addition of NS to LOR would improve the success of epidural catheter placement. METHODS: One-hundred patients were randomized to thoracic epidural analgesia (TEA) utilizing LOR-alone or loss of resistance plus nerve stimulation (LOR + NS). The primary endpoint was rate of success, defined as loss of sensation following test dose. Secondary endpoints included performance time. An intention-to-treat analysis was planned, but a per-protocol analysis was performed to investigate the success rate when stimulation was achieved. RESULTS: In the intention-to-treat analysis there was no difference in success rates (90% vs 82% [LOR + NS vs LOR-alone]; P = 0.39). The procedural time increased in the LOR + NS group (33.9 ± 12.8 vs 24.0 ± 8.0 min; P < 0.001). The per-protocol analysis found a statistically higher success rate for the LOR + NS group compared to the LOR-alone group (98% vs. 82%; P = 0.017) when only patients in whom stimulation was achieved were included. CONCLUSIONS: Addition of NS technique did not statistically improve the success rate for epidural placement when analyzed in an intention-to-treat format and was associated with a longer procedural time. In a per-protocol analysis a statistically higher success rate for patients in whom stimulation was obtained highlights the potential benefit of adding NS to LOR. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03087604 on 3/22/2017; Institutional Review Board Wake Forest School of Medicine IRB00039522, Food and Drug Administration Investigational Device Exemption: G160273.

Pharmacokinetics of testosterone therapies in relation to diurnal variation of serum testosterone levels as men age.

BACKGROUND: To improve symptoms associated with testosterone deficiency, many testosterone therapies are available that aim to restore serum testosterone (T) levels to the normal physiologic range. The magnitude, frequency, and duration between peak and trough T concentrations vary with route of administration, and none reflect normal endogenous daily diurnal T variations. OBJECTIVE: To compare pharmacokinetic profiles of serum T from approved T formulations with endogenous diurnal T variations in young and older men, and to consider whether there may be value in mimicking the diurnal T rhythmicity with exogenous testosterone therapies as men age. MATERIALS AND METHODS: A literature search of studies examining the diurnal variation of endogenous T in healthy men and men with testosterone deficiency was performed using PubMed in January 2020. Additional searches for serum T pharmacokinetic profiles of various testosterone therapy formulations were also conducted. Prescribing information for various T formulations was also reviewed. DISCUSSION AND CONCLUSION: Endogenous diurnal T variation is well described and appears to be blunted naturally as men age. Men with testosterone deficiency lack diurnal T variation and exhibit a flatter T profile compared with eugonadal men. Some T replacement options provide intraday T level variations similar to normal circadian secretion, and others provide a flatter exposure profile reflective of depot release. Others provide profiles that exceed the frequency and physiologic range of the natural diurnal variation of T. All exogenous T replacement dosing targets an increase in average T levels to within the normal physiologic range and improves symptoms associated with low T, but no single testosterone therapy can exactly mimic the normal diurnal T patterns seen in younger men and the blunted circadian T secretion of older men.

Testosterone Therapy and Cardiovascular Risk: A Critical Analysis of Studies Reporting Increased Risk.

BACKGROUND: Treatment of "adult-onset hypogonadism" (AOH) with exogenous testosterone therapy (TTh) to raise serum testosterone (T) levels may influence cardiovascular (CV) risk factors in patients with AOH, whereas low endogenous T levels are associated with an increased CV risk and mortality. AIM: To critically evaluate studies reporting increased CV risk associated with TTh and to provide an overview of the risks and benefits of restoring T levels through exogenous TTh. METHODS: A review of publications focusing on the association between TTh and increased CV risk was conducted, and the study methodologies and conclusions of each were critically evaluated. Further, recent clinical and epidemiological studies associating AOH or TTh with a change in CV risk, and pertinent hematologic and vascular effects noted in animal studies and in vitro, as well as in clinical practice were also reviewed. OUTCOMES: A review of the literature shows that untreated testosterone deficiency and/or low T is associated with an increase in CV risk and adverse outcomes, with numerous studies and meta-analyses to support a positive association between exogenous TTh and an improvement in CV risk factors in men with AOH. RESULTS: Numerous studies in the literature demonstrate the positive benefits of using TTh; however, since 2013, some publications have suggested a link to increased CV risk associated with TTh. A number of these studies retrospectively analyzed insurance claims databases using diagnosis codes, procedures codes, and prescription information. Many reviews published since have pointed out the methodological flaws and debatable conclusions of these studies. CLINICAL IMPLICATIONS: A careful assessment of the patient's current health status and CV risk factors should be weighed against the benefits and possible risks resulting from TTh, and consideration should be given to deferring treatment pending resolution or stabilization of CV disease or risk factors. STRENGTHS & LIMITATIONS: In this review, we provide an in-depth analysis of studies reporting increased CV risk with TTh. Many of the studies were not well-designed, randomized, double-blind, prospective clinical trials but rather post hoc analyses of cohort data. These studies may reflect bias in how treatment and nontreatment decisions are made or reflect conclusions based on widely cited methodological flaws. CONCLUSION: Appropriate patient selection supported by low pre-treatment T levels and monitoring T levels during treatment with the goal of achieving and maintaining physiologic levels all contribute to the safe and effective use of TTh in men with AOH. Khera M, Miner M, Jaffe J, et al. Testosterone Therapy and Cardiovascular Risk: A Critical Analysis of Studies Reporting Increased Risk. J Sex med 2021;18:83-98.

Testosterone Use in Adolescent Males: Current Practice and Unmet Needs.

Testosterone replacement therapy (TRT) is routinely prescribed in adolescent males with constitutional delay of growth and puberty (CDGP) or hypogonadism. With many new testosterone (T) formulations entering the market targeted for adults, we review current evidence and TRT options for adolescents and identify areas of unmet needs. We searched PubMed for articles (in English) on testosterone therapy, androgens, adolescence, and puberty in humans. The results indicate that short-term use of  T enanthate (TE) or oral  T undecanoate is safe and effective in inducing puberty and increasing growth in males with CDGP. Reassuring evidence is emerging on the use of transdermal  T to induce and maintain puberty. The long-term safety and efficacy of TRT for puberty completion and maintenance have not been established. Current  TRT regimens are based on consensus and expert opinion, but evidence-based guidelines are lacking. Limited guidance exists on when and how  T should be administered and optimal strategies for monitoring therapy once it is initiated. Only  TE and  T pellets are US Food and Drug Administration approved for use in adolescent males in the United States. Despite the introduction of a wide variety of new  T formulations, they are designed for adults, and their metered doses are difficult to titrate in adolescents. In conclusion, TRT in adolescent males is hindered by lack of long-term safety and efficacy data and limited options approved for use in this population. Additional research is needed to identify the route, dose, duration, and optimal timing for TRT in adolescents requiring androgen therapy.

Impact of creatinine screening on contrast-induced nephropathy following computerized tomography for stroke.

OBJECTIVE: This study sought to evaluate rates of acute kidney injury in patients undergoing contrast-enhanced computerized tomography for acute stroke in the emergency department (ED) before and after the cessation of creatinine screening. METHODS: This retrospective study compared ED patients receiving contrast-enhanced imaging for suspected acute stroke with and without protocolized creatinine screening. The primary outcome was CIN, defined as an increase in serum creatinine of 0.3 mg/dl within 48 hours or 50% above baseline within 7 days after contrast administration. Secondary outcomes consisted of CIN based on other definitions, renal impairment greater than 30 days from contrast administration, hemodialysis, and mortality. Outcomes were compared using difference of proportions and odds ratios with 95% confidence intervals. RESULTS: This study included 382 subjects, with 186 and 196 in the screening and post-screening cohorts, respectively. No significant differences were observed for CIN (7.0% vs 7.1%, difference 0.1% [95% CI -5.6-5.1%], OR 1.02 [95% CI 0.47-2.24]), renal impairment greater than 30 days post-contrast (8.4% vs 7.5%, OR 0.88 [0.38-2.07]), or mortality (index visit: 4.8% vs 2.6%, OR 0.51 [0.17-1.57], 90-day follow-up: 6.7% vs 4.0%, OR 0.58 [0.22-1.53]). No patients from either group required hemodialysis. CONCLUSIONS: The elimination of creatinine screening prior to obtaining contrast-enhanced computerized tomography in patients with suspected acute stroke did not adversely affect rates of CIN, hemodialysis, or mortality at a comprehensive stroke center.

Safety of a New Subcutaneous Testosterone Enanthate Auto-Injector: Results of a 26-Week Study.

INTRODUCTION: Patients with testosterone deficiency (TD) can be treated with exogenous testosterone (T) to achieve and maintain physiologic T levels and prevent negative clinical symptoms; with many testosterone replacement therapies currently available, this registration safety study was conducted to further characterize the clinical profile of chronically administered, concentration-guided subcutaneous testosterone enanthate (TE) dosing. AIM: The purpose of this study was to confirm the safety and characterize the pharmacokinetic (PK) profile of the subcutaneous TE auto-injector (SCTE-AI) in adult men with TD. METHODS: In this phase III, 26-week study, 133 men 18-75 years of age with symptomatic TD self-administered SCTE-AI 75 mg once weekly for 6 weeks from July 2015 to June 2016. Dosing was adjusted when indicated to 50 mg or 100 mg to maintain T trough levels between 350 and 650 ng/dL (12.1-22.5 nmol/L). PK data were collected from a subgroup of patients receiving 75 mg SCTE-AI through week 12. Safety, including ambulatory blood pressure monitoring (ABPM), lipid levels, and adverse drug reactions, and PK were assessed. MAIN OUTCOME MEASURES: The main outcomes were the documentation of the reproducibility of trough concentration-guided exposure to SCTE, 6-month safety profile, and PK data for the 75 mg dose SCTE. RESULTS: In total, 34 patients (25.6%) experienced adverse drug reactions; the most frequently reported were increased hematocrit (≥52%) in 10 patients (7.5%), injection-site hemorrhage in 6 patients (4.5%), injection-site bruising in 4 patients (3.0%), and increased prostate-specific antigen in 4 patients (3.0%). By week 26, mean systolic and diastolic blood pressure (BP) measured in the clinic increased by 3.4 mmHg (125.6-129.0 mmHg) and 1.8 mmHg (78.2-80.0 mmHg), respectively, from baseline. At week 12, ABPM showed 24-hour mean systolic and diastolic BP increases of 3.7 mmHg and 1.3 mmHg, respectively. All measured lipid fractions were below baseline levels at week 26. T, TE, dihydrotestosterone, and estradiol increased from weeks 1-12. T trough levels ranged from 300-650 ng/dL (10.4-22.5 nmol/L) in 82.4% and 83.2% of patients at weeks 12 and 26, respectively. Of the 965 assessed injections, mild pain was reported by 1 patient. CLINICAL IMPLICATIONS: Dosing with SCTE is well-tolerated overall, yet associated with a numerically small mean systolic BP increase. STRENGTHS & IMPLICATIONS: This study used a standardized ABPM protocol, confirming a numerically small systolic BP increase may be associated with reintroducing therapeutic T exposure in hypogonadal men. It is unknown at this time whether this applies with all routes of T supplementation. CONCLUSION: SCTE-AI has a favorable safety profile and is well-tolerated, with a stable PK profile. Gittelman M, Jaffe JS, Kaminetsky JC. Safety of a New Subcutaneous Testosterone Enanthate Auto-Injector: Results of a 26-Week Study. J Sex Med 2019;16:1741-1748. Clinicaltrials.gov Identifier: NCT02504541.

Comparison of Curved and Straight Anchor Insertion for Bankart Repair.

The quality of Bankart repair may be compromised by the presence of glenoid perforation during suture anchor placement. The purpose of this study was to compare the rate of glenoid perforation and biomechanical strength of antero-inferior suture anchors placed with a curved vs a traditional straight technique through an anteroinferior portal. Ten bilateral pairs of fresh human cadaveric shoulders were randomized to either a curved or a straight suture anchor insertion technique. An anteroinferior portal was used to place a 1.5-mm soft anchor in the anteroinferior glenoid (5:30 position for right shoulders). Anatomic dissection was performed, and the maximum load of each anchor was measured using a materials testing system. The overall rate of glenoid perforation by the anteroinferior anchor was 50%. The rate of glenoid perforation was 40% in the straight group and 60% in the curved group (P=.41). The median maximum load was 86 N in the straight group and 137 N in the curved group (P=.23). The median maximum load of the anchors that did perforate the glenoid was 102 N and of those that did not was 118 N (P=.72). The mode of failure was suture anchor pullout in all except one specimen. The curved guide was not superior to the traditional straight guide in terms of the rate of glenoid perforation or the maximum load of the suture anchors. Anterior cortical perforation of the glenoid during anteroinferior suture anchor placement is common with both techniques. [Orthopedics. 2019; 42(2):e242-e246.].

Preprocedural checklist for regional anesthesia: impact on the incidence of wrong site nerve blockade (an 8-year perspective).

BACKGROUND: The term "Wrong-Site Surgery (WSS)" is commonly associated with surgical procedures; however, The Joint Commission (TJC) considers any invasive procedure, not just a surgical procedure, performed on the wrong side, at the wrong site, or on the wrong patient to be a WSS. For anesthesia providers, this means that a wrong-site nerve block (WSNB) also constitutes a WSS and would be considered a sentinel event by TJC. In an attempt to combat WSNB, the American Society of Regional Anesthesia and Pain Medicine published guidelines in 2014 recommending the use of a preprocedural checklist before performing regional blocks. The effectiveness of such a checklist, however, to reduce the occurrence of WSNB has not yet been demonstrated. We hypothesized that the introduction of a preprocedural checklist specific for regional anesthesia would be associated with a lower rate of WSNB procedures. METHODS: A retrospective review was performed to compare the incidence of WSNB 2 years before, to 6 years after the implementation of a preprocedural checklist specific to regional anesthesia. RESULTS: Prior to checklist implementation, 4 WSNB events occurred during 10 123 procedures (3.95 per 10 000 (95% CI 1.26 to 9.53). Following implementation, WSNB events occurred during 35 890 procedures (0 per 10 000 (95% CI 0 to 0.84)); p=0.0023. CONCLUSIONS: Implementation of a regional anesthesia specific preprocedural checklist was associated with a significantly lower incidence of WSNB procedures. While prospective controlled studies would be required to demonstrate causation, this study suggests that for regional anesthesia procedures, a preprocedural checklist may positively impact patient safety.

A 52-Week Study of Dose Adjusted Subcutaneous Testosterone Enanthate in Oil Self-Administered via Disposable Auto-Injector.

PURPOSE: In this open label, single arm, dose blinded, 52-week registration phase study we evaluated the efficacy and safety of a subcutaneous testosterone enanthate auto-injector administered weekly to men with hypogonadism. MATERIALS AND METHODS: A total of 150 patients were initiated on a 75 mg subcutaneous testosterone enanthate auto-injector self-administered weekly. Dose adjustments were made at week 7 to 50, 75 or 100 mg testosterone enanthate based on the week 6 total testosterone trough concentration. If required, dose adjustments continued through the extended treatment phase. Pharmacokinetic and clinical laboratory parameters, treatment emergent adverse events and injection site reactions were captured. RESULTS: The primary end point was met since 92.7% of patients achieved an average total testosterone concentration of 300 to 1,100 ng/dl (mean ± SD 553.3 ± 127.29) at week 12. A maximum concentration of less than 1,500 ng/dl was achieved by 91.3% of patients and no patient had a level greater than 1,800 ng/dl at week 12. The mean total testosterone trough concentration was 487.2 ± 153.33 ng/dl at week 52. Of the patients more than 95% reported no injection related pain. The most frequently reported treatment emergent adverse events were increased hematocrit, hypertension and increased prostate specific antigen, which led to discontinuation in 30 men. There were no study drug related serious adverse events. CONCLUSIONS: The dose adjusted subcutaneous testosterone enanthate auto-injector demonstrated a steady serum total testosterone pharmacokinetic profile with small peak and trough fluctuations. The device was safe, well tolerated and virtually painless, indicating that this subcutaneous testosterone enanthate auto-injector offers a testosterone delivery system that is a convenient weekly option to treat testosterone deficiency.

Summative Usability Evaluation of the SCTE-AI Device: A Novel Prefilled Autoinjector for Subcutaneous Testosterone Administration.

BACKGROUND: The subcutaneous testosterone enanthate (TE) autoinjector (SCTE-AI) is a single-use, pre-filled, disposable autoinjector intended for testosterone (T) self-administration in adult males with T deficiency. AIM: To evaluate the usability of the market configuration of the SCTE-AI, including packaging and instructions for use (IFU), in order to identify and mitigate any preventable patterns of use errors that could result in harm. METHODS: 4 groups of participants (injection-naïve or injection-experienced patients or caregivers) were randomized to 1 of 3 doses (50, 75, and 100 mg) of TE and either trained (ie, reviewed the IFU and shown how to properly inject) or not trained (only given the IFU). After simulated at-home use, participants were asked questions regarding the comprehensibility of the IFU and the intuitiveness/usability of the device. All tasks were measured as success, use error, or close call (participant initiated an error but recovered in time). MAIN OUTCOME MEASURE: Usability (success rates, errors, and close calls) of the drug/device combination by adult males with T deficiency or their caregivers. RESULTS: 65 patients received 1 dose of TE, and 59 patients received 2 doses. Overall, 99 of 123 (80.5%) attempted injections resulted in administration of 1 full dose. Injection success rates were high and comparable among the various user groups. The most common use error (21 of 24) was due to not holding the autoinjector on the abdomen long enough (at least 8 seconds). Few critical drug delivery and safety errors or close calls were observed. No unmitigated use errors by patients or caregivers were apparent that could result in harm or have a negative impact on treatment. SCTE-AI was well tolerated. CLINICAL IMPLICATIONS: The SCTE-AI development process resulted in a subcutaneous, TE autoinjection device that is intuitive to use, with clear labeling and packaging and an easy-to-understand IFU, providing an option for T-deficient adult males to self-inject subcutaneously at home. STRENGTH & LIMITATIONS: The strengths of the study include use of a patient-ready drug/device combination for self-administration and inclusion of both injection-naïve and injection-experienced patients and caregivers. The main limitation of the study is the presence of observers/cameras that may have distracted or created performance anxiety, potentially contributing to errors. CONCLUSION: Results of this usability validation study indicate that the SCTE-AI device is safe and intuitive to use, with a low potential for harm and is associated with a high rate of injection success, regardless of prior training or experience. Arora S, Moclair B, Murphy K, et al. Summative Usability Evaluation of the SCTE-AI Device: A Novel Prefilled Autoinjector for Subcutaneous Testosterone Administration. J Sex Med 2018;15:1707-1715.

Comparison of Curved and Straight Anchor Insertion for SLAP Repair: A Cadaveric Study.

PURPOSE: To compare a curved drill guide with a straight guide for suture anchor placement into the posterosuperior glenoid from an anterolateral portal with respect to glenoid perforation, drill contact with the suprascapular nerve, and maximum load. METHODS: Ten bilateral pairs of fresh human cadaveric shoulders were randomized to the curved technique on 1 side and the straight technique on the contralateral side. An anterolateral trans-rotator cuff portal was used for placement of anchors at the posterior (11 o'clock right shoulder) and far posterior (10 o'clock right shoulder) positions on the glenoid with a 24-mm drill stop, and the drill tip was marked with ink. Specimens were dissected for glenoid perforation and drill contact with the suprascapular nerve. The maximum load of each anchor was measured using a material testing system. RESULTS: Glenoid perforation occurred in 30% in the curved group and 60% in the straight group overall (P = .01). Ink markings demonstrated a direct hit on the suprascapular nerve in most of the penetrations (13 of 18) but was not significantly different between the curved and straight guides (P = .25). Maximum load of the posterior anchor was greater in the curved group than that in the straight group (199.5 vs 146.7 N, respectively; P = .01). CONCLUSIONS: The curved technique has a lower rate of glenoid perforation and greater maximum load than the straight technique. However, the curved technique can result in glenoid perforation and injury to the suprascapular nerve, and we do not recommend it. CLINICAL RELEVANCE: Placing suture anchors through an anterolateral portal with a curved guide provides a more optimal trajectory with decreased risk of glenoid perforation and superior biomechanical strength than that with the straight guide, but it is not safe.

Single-Injection Adductor Canal Block With Multiple Adjuvants Provides Equivalent Analgesia When Compared With Continuous Adductor Canal Blockade for Primary Total Knee Arthroplasty: A Double-Blinded, Randomized, Controlled, Equivalency Trial.

BACKGROUND: Peripheral nerve blockade is used to provide analgesia for patients undergoing total knee arthroplasty. This study compared a single-injection adductor canal block (SACB) with adjuvants to continuous adductor canal blockade (CACB). The hypothesis was that the 2 groups would have equivalent analgesia at 30 hours after neural blockade. METHODS: This was a double-blinded, randomized, controlled, equivalency trial. Sixty patients were randomized to either the SACB group (20 mL of 0.25% bupivacaine, 1.67 mcg/mL of clonidine, 2 mg of dexamethasone, 150 mcg of buprenorphine, and 2.5 mcg/mL of epinephrine) or the CACB group (20 mL 0.25% of bupivacaine injection with 2.5 mcg/mL of epinephrine followed by an 8 mL/h infusion of 0.125% bupivacaine continued through postoperative day 2). The primary outcome was movement pain scores at 30 hours using the numeric rating scale (NRS). The secondary outcomes included serial postoperative NRS pain scores (rest and movement every 6 hours), opioid consumption, time to first opioid administration, ability to straight leg raise, patient satisfaction, length of stay, and the incidence of nausea/vomiting. RESULTS: An intention-to-treat analysis included 59 patients. The NRS pain scores with movement were equivalent at 30 hours (SACB 5.5 ± 2.8 vs CACB 5.7 ± 2.9 [mean NRS ± standard deviation]; mean difference 0.2 [-1.5 to 1.0 {90% confidence interval}]). All NRS pain scores were equivalent until 42 hours (rest) and 48 hours (rest and movement) with the CACB group having lower pain scores. Other secondary outcomes were not statistically different. CONCLUSION: An SACB provides equivalent analgesia for up to 36 hours after block placement when compared with a CACB for patients undergoing total knee arthroplasty, though a CACB was favored at 42 hours and beyond.

Spontaneous Bilateral Internal Carotid Artery Dissections in a Young Female with Headache.

Spontaneous cervical artery dissection (sCAD) occurs when the intimal lining separates from the outer wall of the artery. Although rare, it is a common cause of stroke in young people. Presentations range from isolated headache to severe stroke symptoms. A 41-year-old woman with minimal past medical history presented with left-sided headache and transient right leg weakness and numbness. The patient underwent computed tomography (CT) angiography of the neck that showed bilateral internal carotid artery dissections with a relative stenosis from pseudoaneurysm formation on the left. She was placed on a heparin drip and transitioned to warfarin but subsequently required stent placement 10 days later. If this patient had not undergone CT angiography at the time of presentation, she might have suffered significant morbidity and possible mortality.

Transversus abdominis plane block as the primary anesthetic for peritoneal dialysis catheter surgery.

STUDY OBJECTIVE: The primary goal of this study was to determine whether transversus abdominis plane (TAP) blocks were effective as the primary anesthetic technique for insertion and/or removal of peritoneal dialysis catheters. DESIGN: This study is a descriptive case series investigation. SETTING: Operating rooms at a tertiary care academic medical center. PATIENTS: Twenty-four patients, American Society of Anesthesiologists (ASA) physical status 3 and 4, were included in this study. INTERVENTIONS: Patients who had received a TAP block preoperatively for open surgical insertion or removal of a peritoneal dialysis catheter over a 26-month period with the intent of the block to serve as the primary anesthetic were included in this study. MEASUREMENTS: Preoperative and intraoperative sedative medications and local anesthetic medications were analyzed. The primary outcome of the study was the ability of the TAP block to provide surgical anesthesia as determined by a lack of need to convert to general anesthesia (defined by placement of an airway device, use of volatile anesthetics, intraoperative propofol infusion dose equal to or greater than 100 µg kg(-1) min(-1)). Secondary outcomes included analysis of any complications from the higher concentrations of local anesthetics required for surgical block. MANI RESULTS: Of 24 patients, 21 underwent the procedure without conversion to general anesthesia as defined above. No complications related to local anesthetics were found. CONCLUSION: Transversus abdominis plane blockade can be successful at serving as the primary anesthetic modality for the insertion and/or removal of a peritoneal dialysis catheter by open-surgical approach. There were no systemic toxic effects or other complications recorded.

Ultrasound-Guided Continuous Superficial Radial Nerve Block for Complex Regional Pain Syndrome.

Although there are many potentially effective therapeutic options for complex regional pain syndrome (CRPS), no definitive treatment exists. Therefore, patients often exhaust both medical and surgical treatment options attempting to find relief for their symptoms. As pain control and restoration of physical movement are primary treatment goals, strategies that include regional anesthesia techniques are commonly employed, but potentially underutilized, treatment modalities. The authors present a patient with refractory CRPS that had significant improvement in both pain control and the ability to tolerate intensive physical therapy following the placement of a superficial radial nerve catheter and an infusion of local anesthetic for 6 days as part of a multimodal analgesic regimen. This treatment approach also assisted in the decision-making process related to future treatment options. Although the use of regional anesthesia and perineural infusions of local anesthetic have previously been described as viable treatment options for CRPS, this case report represents the first known use of a superficial radial nerve catheter for treating CRPS as well as the first description of a technique for placing a superficial radial nerve (SRN) catheter using ultrasound guidance.

An Evaluation of Ultrasound-Guided Adductor Canal Blockade for Postoperative Analgesia After Medial Unicondylar Knee Arthroplasty.

BACKGROUND: Unicondylar knee arthroplasty (UKA) is a commonly performed procedure with significant expected postoperative pain. Peripheral nerve blocks are 1 analgesic option, but some approaches may decrease quadriceps motor strength and interfere with early ambulation. In this study, we compared the analgesia provided by an adductor canal block (ACB) and a psoas compartment block (PCB) after UKA. We hypothesized that the ACB would provide equivalent analgesia, defined as a difference of <2 points on the pain scale (0-10 numeric rating scale [NRS]), at rest and with movement 6 hours after block placement. METHODS: One hundred fifty patients undergoing medial UKA were randomly assigned to receive either an ACB or a PCB with 0.25% bupivacaine, 5 µg/mL epinephrine, and 1.67 µg/mL clonidine. All patients received multimodal analgesics, sham blockade at the alternate site, and a posterior capsule injection during surgery. Patients and observers were blinded to treatment groups. The primary end points were NRS pain scores with rest and movement at 6 hours. Secondary end points included quadriceps muscle strength at 6 hours (0-5 [5 being full strength]; Medical Research Council scale) as well as NRS pain scores, opioid consumption, and opioid-related side effects over 24 hours. RESULTS: One hundred forty-seven patients were analyzed. Pain scores were equivalent at 6 hours with rest (ACB 1.0 ± 2 vs PCB 1.1 ± 2.2 [mean NRS ± SD]; 95% confidence interval of mean difference, -0.8 to 0.6; P < 0.0001) and with movement (ACB 1.6 ± 2.6 vs PCB 1.5 ± 2.8; 95% confidence interval of mean difference, -0.8 to 0.9; P < 0.0001). In addition, pain scores at rest and with movement at 12, 18, and 24 hours were equivalent. Quadriceps motor strength was significantly increased in the ACB group (Medical Research Council scale score, 4.0 ± 1.1 vs 2.5 ± 1.3 [mean ± SD]; P < 0.0001). No significant differences were found between groups for time to first analgesic or for cumulative opioid consumption at 6, 12, 18, or 24 hours. Other than an increase in the incidence of pruritus in the ACB group at 6 hours, there were no differences in opioid-related side effects. CONCLUSIONS: An ACB provides equivalent analgesia after medial UKA when compared with a PCB. In addition, the ACB caused significantly less motor weakness. An ACB should be considered for postoperative analgesia after medial UKA.

Pharmacokinetic Profile of Subcutaneous Testosterone Enanthate Delivered via a Novel, Prefilled Single-Use Autoinjector: A Phase II Study.

INTRODUCTION: Hypogonadism is one of the most common male endocrine problems. Although many treatments are currently available, unmet need exists for new testosterone (T) replacement therapies that are simple to administer and use, are safe, and mimic physiologic T levels. AIM: The study aim was to determine the pharmacokinetics (PK), safety, and tolerability of T enanthate (TE) administered via a novel single-use autoinjector system, which was designed to eject high-viscosity solutions from a prefilled syringe fitted with a five-eighths-inch 27-gauge needle. METHODS: Thirty-nine men with hypogonadism entered this dose-finding, open-label, parallel-group study. Patients were washed out of their topical T regimens and randomized to receive 50 or 100 mg of subcutaneous (SC) TE weekly. The reference group were patients with hypogonadism who were maintained on standard 200-mg intramuscular (IM) TE. MAIN OUTCOME MEASURE: The primary outcome measure was the PK profile of SC TE, analyzed in reference to T levels used by the Food and Drug Administration to approve T products. Secondary outcome measures were safety and tolerability assessments. RESULTS: Both doses of SC TE achieved normal average concentrations of serum T within a 168-h dosing interval after injection. Concentration ranges were similar at all time points following 50-mg SC TE injections and following the third injection in the 100-mg arm. Mean steady-state T concentration at week 6 was 422.4 and 895.5 ng/dL for the 50- and 100-mg SC TE arms, respectively. SC TE demonstrated PK dose proportionality. SC TE restored normal serum T with low variation relative to 200-mg IM without clinically significant adverse events. CONCLUSIONS: Administration of TE via this novel injection system restored T levels to normal range in men with hypogonadism. SC TE dosed weekly demonstrated steady, dose-proportional measures of exposure and was well-tolerated. Kaminetsky J, Jaffe JS, Swerdloff RS. Pharmacokinetic profile of subcutaneous testosterone enanthate delivered via a novel, prefilled single-use autoinjector: A phase II study. Sex Med 2015;3:263-273.