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RationaleCannabidiol (CBD) reduces craving in animal models of alcohol and cocaine use and is known to modulate nicotinic receptor function, suggesting that it may alleviate symptoms of nicotine withdrawal. However, preclinical evaluation of its efficacy is still lacking.ObjectivesThe goal of this study was to test the preclinical efficacy of a chronic CBD treatment in reducing nicotine dependence using measures of withdrawal symptoms including somatic signs, hyperalgesia, and weight gain during acute and protracted abstinence.MethodsMale and female Wistar rats were made dependent on nicotine using osmotic minipumps (3.15 mg/kg/day) for 2 weeks, after which minipumps were removed to induce spontaneous withdrawal. Three groups received CBD injections at doses of 7.5, 15, and 30 mg/kg/day for 2 weeks, starting 1 week into chronic nicotine infusion. The control groups included rats with nicotine minipumps that received vehicle injections of sesame oil instead of CBD; rats implanted with saline minipumps received sesame oil injections (double vehicle) or the highest dose of CBD 30 mg/kg/day. Throughout the experiment, serum was collected for determination of CBD and nicotine concentrations, mechanical sensitivity threshold and withdrawal scores were measured, and body weight was recorded.ResultsCBD prevented rats from exhibiting somatic signs of withdrawal and hyperalgesia during acute and protracted abstinence. There was no dose-response observed for CBD, suggesting a ceiling effect at the doses used and the potential for lower effective doses of CBD. The saline minipump group did not show either somatic signs of withdrawal or hyperalgesia during acute and protracted abstinence, and the highest dose of CBD used (30 mg/kg/day) did not alter these results.ConclusionsThis preclinical study suggests that using CBD as a strategy to alleviate the withdrawal symptoms upon nicotine cessation may be beneficial.

RationaleCannabidiol (CBD) reduces craving in animal models of alcohol and cocaine use and is known to modulate nicotinic receptor function, suggesting that it may alleviate symptoms of nicotine withdrawal. However, preclinical evaluation of its efficacy is still lacking.ObjectivesThe goal of this study was to test the preclinical efficacy of a chronic CBD treatment in reducing nicotine dependence using measures of withdrawal symptoms including somatic signs, hyperalgesia, and weight gain during acute and protracted abstinence.MethodsMale and female Wistar rats were made dependent on nicotine using osmotic minipumps (3.15 mg/kg/day) for 2 weeks, after which minipumps were removed to induce spontaneous withdrawal. Three groups received CBD injections at doses of 7.5, 15, and 30 mg/kg/day for 2 weeks, starting 1 week into chronic nicotine infusion. The control groups included rats with nicotine minipumps that received vehicle injections of sesame oil instead of CBD; rats implanted with saline minipumps received sesame oil injections (double vehicle) or the highest dose of CBD 30 mg/kg/day. Throughout the experiment, serum was collected for determination of CBD and nicotine concentrations, mechanical sensitivity threshold and withdrawal scores were measured, and body weight was recorded.ResultsCBD prevented rats from exhibiting somatic signs of withdrawal and hyperalgesia during acute and protracted abstinence. There was no dose-response observed for CBD, suggesting a ceiling effect at the doses used and the potential for lower effective doses of CBD. The saline minipump group did not show either somatic signs of withdrawal or hyperalgesia during acute and protracted abstinence, and the highest dose of CBD used (30 mg/kg/day) did not alter these results.ConclusionsThis preclinical study suggests that using CBD as a strategy to alleviate the withdrawal symptoms upon nicotine cessation may be beneficial.

Infusion pumps have been widely used in clinical settings for the administration of medications and fluids. We present the digital droplet infusion (DDI) device, a low-cost, high-precision digital infusion system, utilizing a microfluidic discretization unit to convert continuous flow into precisely delivered droplet aliquots and a valving unit to control the duration and frequency of flow discretization. The DDI device relies on a distinct capillarity-dominated process of coalescence and pinch-off of droplets for flow digitization, which is monitored by a pair of conductive electrodes located before and after the junction. The digital feedback-controlled flow rate can be employed to adjust a solenoid valve for refined infusion management. With this unique digital microfluidic approach, the DDI technology enables a simple yet powerful infusion system with an ultrahigh resolution of digital droplet transfer volume, as small as 57 nL, which is three orders of magnitude lower than that of clinical standard infusion pumps, as well as a wide range of digitally adjustable infusion rates ranging from 0.1 mL h-1 to 10 mL h-1, in addition to an array of programmable infusion profiles and safety features. Its modular design enables fast assembly using only off-the-shelf and 3D-printed components. Overall, benefiting from its simple device architecture and excellent infusion performance, the DDI technology has great potential to become the next-generation clinical standard for drug delivery with its high precision and ultimate portability at a low cost.

BACKGROUND Continuous peripheral nerve blocks can be administered as continuous infusion, patient-controlled boluses, automated boluses, or a combination of these modalities. MATERIAL AND METHODS Ten patients undergoing either ankle (5) or distal radius (5) open reduction and internal fixation received single-injection ropivacaine sciatic nerve block or infraclavicular brachial plexus block and catheter. Infusion pumps were set to begin administering additional ropivacaine 6 h following the initial block as automated boluses supplemented with patient-controlled boluses. RESULTS Patients had similar pain scores when compared to previously published controls; however, local anesthetic consumption was lower in the patients, resulting in increased infusion and analgesia duration by 1 or more days in each group. CONCLUSIONS For infraclavicular and popliteal sciatic catheters, automated boluses may provide a longer duration of analgesia than continuous infusions following painful hand and ankle surgeries, respectively.

BackgroundCritically ill neonates and pediatric patients commonly require multiple low flow infusions. Volume limitations are imposed by small body habitus and co-morbidities like cardiopulmonary disease, renal failure, or fluid overload. Vascular access is limited by diminutive veins. Maintenance fluids or parenteral nutrition in conjunction with actively titrated infusions such as insulin, fentanyl, prostaglandins, inotropes and vasopressors may necessitate simultaneous infusions using a single lumen to maintain vascular catheter patency. This requirement for multiple titratable infusions requires concentrated medications at low flows, rather than more dilute drugs at higher flows that in combination may volume overload small infants.AimTo determine whether carrier fluid reduces variability that variability of low flow drug infusions is proportional to syringe size in pediatric critical care.MethodsWe assessed concentrations of orange "drug" in a 0.2 mL/h low flow clinical model with blue dyed carrier fluid at 5 mL/h, using 3-, 10-, or 60-mL syringes. A graduated volumetric pipette was used to measure total flow. Mean time to target concentration was 30, 21, and 46 min in 3-, 10-, and 60-mL syringes, respectively (P = 0.42). After achieving target concentration, more dilute drug was delivered by 60-mL (P < 0.001) and 10-mL syringes (P = 0.04) compared to 3-mL syringes. Drug overdoses were observed during the initial 45 min of infusion in 10-and 60-mL syringes. Total volumes infused after target concentration were less in the 60-mL condition compared to 3-mL (P < 0.01) and 10-mL (P < 0.001) syringes.ResultsLinear mixed effects models demonstrated lesser delivered drug concentrations in the initial 30 min by 3-mL compared to 10-and 60-mL syringes (P = 0.005 and P < 0.001, respectively) but greater drug concentrations and total infused drug in the subsequent 30-60 and 60-90 min intervals with the 3- and 10-mL compared to 60-mL syringes.ConclusionWith carrier fluid, larger syringes were associated with significantly less drug delivery, less total volume delivered, and other flow problems in our low flow drug model. Carrier fluid should not be used to compensate for inappropriately large syringes in critical low flow drug infusions.

AimTo assess the associations between demographic and clinical characteristics and sensor glucose metrics in young children with type 1 diabetes, using masked, continuous glucose monitoring data from children aged 2 to < 8 years.Research design and methodsThe analysis included 143 children across 14 sites in the USA, enrolled in a separate clinical trial. Eligibility criteria were: age 2 to 10.0 mmol/l) and a median of ~1 h/day in hypoglycaemia (

Purpose of reviewThis review considers statistical issues in the design and analysis of the studies used to develop long-acting formulations of antiretrovirals for pre-exposure prophylaxis (PrEP).Recent findingAn abundant pipeline of products is maturing. Accelerating their evaluation as clinical products requires abandonment of noninferiority standards. Randomized trials should be based on the comparison of principled but innovative estimates of background HIV risk and enrich enrollment for those who do not desire current PrEP products. At every stage of testing, innovative analyses can be applied to help inform and accelerate later studies.SummaryThe development of new long-acting PrEP regimens can be accelerated by innovations in design, ingenuity in synthesizing data sources, and application of causal inference methods.

BACKGROUND: We determined whether intrathecally delivering the same daily dose of morphine (MS) at a fixed concentration of 25 mg/mL by periodic boluses versus continuous infusion would reduce intrathecal mass (IMs) formation in dogs. METHODS: Adult dogs (hound cross, n = 32) were implanted with intrathecal catheters connected to SynchroMed II infusion pumps. Animals were randomly assigned to receive infusion of 0.48 mL/day of saline or MS dosing (12 mg/day at 25 mg/mL) as boluses: x1 (q24hour), x2 (q12hour), x4 (q6hour), or x8 (q3hour) given at the rate of 1000 μL/hour, or as a continuous infusion (25 mg/mL/20 μL/hour). RESULTS: With IT saline, minimal pathology was noted. In contrast, animals receiving morphine displayed spinally compressing durally derived masses with the maximal cross-sectional area being greatest near the catheter tip. Histopathology showed that IMs consisted of fibroblasts in a collagen (type 1) matrix comprised of newly formed collagen near the catheter and mature collagen on the periphery of the mass. The rank order of median cross-sectional mass area (mm2 ) was: Saline: 0.7 mm2 ; x2: 1.8 mm2 ; x4: 2.7 mm2 ; x1: 2.7 mm2 ; x8: 4.2 mm2 ; Continuous: 8.1 mm2 , with statistical difference from saline being seen with continuous (p

ObjectiveTo evaluate end-user acceptance and the effect of a commercial handheld decision support device in pediatric intensive care settings. The technology, pac2, was designed to assist nurses in calculating medication dose volumes and infusion rates at the bedside.Materials and methodsThe devices, manufactured by InformMed Inc., were deployed in the pediatric and neonatal intensive care units in 2 health systems. This mixed methods study assessed end-user acceptance, as well as pac2's effect on the cognitive load associated with bedside dose calculations and the rate of administration errors. Towards this end, data were collected in both pre- and postimplementation phases, including through ethnographic observations, semistructured interviews, and surveys.ResultsAlthough participants desired a handheld decision support tool such as pac2, their use of pac2 was limited. The nature of the critical care environment, nurses' risk perceptions, and the usability of the technology emerged as major barriers to use. Data did not reveal significant differences in cognitive load or administration errors after pac2 was deployed.Discussion and conclusionDespite its potential for reducing adverse medication events, the commercial standalone device evaluated in the study was not used by the nursing participants and thus had very limited effect. Our results have implications for the development and deployment of similar mobile decision support technologies. For example, they suggest that integrating the technology into hospitals' existing IT infrastructure and employing targeted implementation strategies may facilitate nurse acceptance. Ultimately, the usability of the design will be essential to reaping any potential benefits.

Glial cell line-derived neurotrophic factor (GDNF) has demonstrated neurorestorative and neuroprotective effects in rodent and nonhuman primate models of Parkinson's disease. However, continuous intraputamenal infusion of GDNF (100 µg/day) resulted in multifocal cerebellar Purkinje cell loss in a 6-month toxicity study in rhesus monkeys. It was hypothesized that continuous leakage of GDNF into the cerebrospinal fluid compartment during the infusions led to down-regulation of GDNF receptors on Purkinje cells, and that subsequent acute withdrawal of GDNF then mediated the observed cerebellar lesions. Here we present the results of a 9-month toxicity study in which rhesus monkeys received intermittent intraputamenal infusions via convection-enhanced delivery. Animals were treated with GDNF (87.1 µg; N = 14) or vehicle (N = 6) once every 4 weeks for a total of 40 weeks (11 treatments). Four of the GDNF-treated animals were utilized in a satellite study assessing the impact of concomitant catheter repositioning prior to treatment. In the main study, eight animals (5 GDNF, 3 control) were euthanized at the end of the treatment period, along with the four satellite study animals, while the remaining eight animals (5 GDNF, 3 control) were euthanized at the end of a 12-week recovery period. There were no GDNF-related adverse effects and in particular, no GDNF-related microscopic findings in the brain, spinal cord, dorsal root ganglia, or trigeminal ganglia. Therefore, 87.1 µg/4 weeks is considered the no observed adverse effect level for GDNF in rhesus monkeys receiving intermittent, convection-enhanced delivery of GDNF for 9 months.

BackgroundIt remains unknown whether continuous or scheduled intermittent bolus local anesthetic administration is preferable for transversus abdominis plane (TAP) catheters. We therefore tested the hypothesis that when using TAP catheters, providing local anesthetic in repeated bolus doses increases the cephalad-caudad cutaneous effects compared with a basal-only infusion.MethodsBilateral TAP catheters (posterior approach) were inserted in 24 healthy volunteers followed by ropivacaine 2 mg/mL administration for a total of 6 hours. The right side was randomly assigned to either a basal infusion (8 mL/h) or bolus doses (24 mL administered every 3 hours for a total of 2 bolus doses) in a double-masked manner. The left side received the alternate treatment. The primary end point was the extent of sensory deficit as measured by cool roller along the axillary line at hour 6 (6 hours after the local anesthetic administration was initiated). Secondary end points included the extent of sensory deficit as measured by cool roller and Von Frey filaments along the axillary line and along a transverse line at the level of the anterior superior iliac spine at hours 0 to 6.ResultsAlthough there were statistically significant differences between treatments within the earlier part of the administration period, by hour 6 the difference in extent of sensory deficit to cold failed to reach statistical significance along the axillary line (mean = 0.9 cm; SD = 6.8; 95% confidence interval -2.0 to 3.8; P = .515) and transverse line (mean = 2.5 cm; SD = 10.1; 95% confidence interval -1.8 to 6.8; P = .244). Although the difference between treatments was statistically significant at various early time points for the horizontal, vertical, and estimated area measurements of both cold and mechanical pressure sensory deficits, no comparison remained statistically significant by hour 6.ConclusionsNo evidence was found in this study involving healthy volunteers to support the hypothesis that changing the local anesthetic administration technique (continuous basal versus hourly bolus) when using ropivacaine 0.2% and TAP catheters at 8 mL/h and 24 mL every 3 hours significantly influences the cutaneous effects after 6 hours of administration. Additional research is required to determine whether changing variables (eg, local anesthetic concentration, basal infusion rate, bolus dose volume, and/or interval) would provide different results.

BackgroundIt remains unknown whether continuous or scheduled intermittent bolus local anesthetic administration is preferable for transversus abdominis plane (TAP) catheters. We therefore tested the hypothesis that when using TAP catheters, providing local anesthetic in repeated bolus doses increases the cephalad-caudad cutaneous effects compared with a basal-only infusion.MethodsBilateral TAP catheters (posterior approach) were inserted in 24 healthy volunteers followed by ropivacaine 2 mg/mL administration for a total of 6 hours. The right side was randomly assigned to either a basal infusion (8 mL/h) or bolus doses (24 mL administered every 3 hours for a total of 2 bolus doses) in a double-masked manner. The left side received the alternate treatment. The primary end point was the extent of sensory deficit as measured by cool roller along the axillary line at hour 6 (6 hours after the local anesthetic administration was initiated). Secondary end points included the extent of sensory deficit as measured by cool roller and Von Frey filaments along the axillary line and along a transverse line at the level of the anterior superior iliac spine at hours 0 to 6.ResultsAlthough there were statistically significant differences between treatments within the earlier part of the administration period, by hour 6 the difference in extent of sensory deficit to cold failed to reach statistical significance along the axillary line (mean = 0.9 cm; SD = 6.8; 95% confidence interval -2.0 to 3.8; P = .515) and transverse line (mean = 2.5 cm; SD = 10.1; 95% confidence interval -1.8 to 6.8; P = .244). Although the difference between treatments was statistically significant at various early time points for the horizontal, vertical, and estimated area measurements of both cold and mechanical pressure sensory deficits, no comparison remained statistically significant by hour 6.ConclusionsNo evidence was found in this study involving healthy volunteers to support the hypothesis that changing the local anesthetic administration technique (continuous basal versus hourly bolus) when using ropivacaine 0.2% and TAP catheters at 8 mL/h and 24 mL every 3 hours significantly influences the cutaneous effects after 6 hours of administration. Additional research is required to determine whether changing variables (eg, local anesthetic concentration, basal infusion rate, bolus dose volume, and/or interval) would provide different results.

A continuous peripheral nerve block (CPNB) consists of a percutaneously inserted catheter with its tip adjacent to a target nerve/plexus through which local anesthetic may be administered, providing a prolonged block that may be titrated to the desired effect. In the decades after its first report in 1946, a plethora of data relating to CPNB was published, much of which was examined in a 2011 Anesthesia & Analgesia article. The current update is an evidence-based review of the CPNB literature published in the interim. Novel insertion sites include the adductor canal, interpectoral, quadratus lumborum, lesser palatine, ulnar, superficial, and deep peroneal nerves. Noteworthy new indications include providing analgesia after traumatic rib/femur fracture, manipulation for adhesive capsulitis, and treating abdominal wall pain during pregnancy. The preponderance of recently published evidence suggests benefits nearly exclusively in favor of catheter insertion using ultrasound guidance compared with electrical stimulation, although little new data are available to help guide practitioners regarding the specifics of ultrasound-guided catheter insertion (eg, optimal needle-nerve orientation). After some previous suggestions that automated, repeated bolus doses could provide benefits over a basal infusion, there is a dearth of supporting data published in the past few years. An increasing number of disposable infusion pumps does now allow a similar ability to adjust basal rates, bolus volume, and lockout times compared with their electronic, programmable counterparts, and a promising area of research is communicating with and controlling pumps remotely via the Internet. Large, prospective studies now document the relatively few major complications during ambulatory CPNB, although randomized, controlled studies demonstrating an actual shortening of hospitalization duration are few. Recent evidence suggests that, compared with femoral infusion, adductor canal catheters both induce less quadriceps femoris weakness and improve mobilization/ambulation, although the relative analgesia afforded by each remains in dispute. Newly published data demonstrate that the incidence and/or severity of chronic, persistent postsurgical pain may, at times, be decreased with a short-term postoperative CPNB. Few new CPNB-related complications have been identified, although large, prospective trials provide additional data regarding the incidence of adverse events. Lastly, a number of novel, alternative analgesic modalities are under development/investigation. Four such techniques are described and contrasted with CPNB, including single-injection peripheral nerve blocks with newer adjuvants, liposome bupivacaine used in wound infiltration and peripheral nerve blocks, cryoanalgesia with cryoneurolysis, and percutaneous peripheral nerve stimulation.

A continuous peripheral nerve block (CPNB) consists of a percutaneously inserted catheter with its tip adjacent to a target nerve/plexus through which local anesthetic may be administered, providing a prolonged block that may be titrated to the desired effect. In the decades after its first report in 1946, a plethora of data relating to CPNB was published, much of which was examined in a 2011 Anesthesia & Analgesia article. The current update is an evidence-based review of the CPNB literature published in the interim. Novel insertion sites include the adductor canal, interpectoral, quadratus lumborum, lesser palatine, ulnar, superficial, and deep peroneal nerves. Noteworthy new indications include providing analgesia after traumatic rib/femur fracture, manipulation for adhesive capsulitis, and treating abdominal wall pain during pregnancy. The preponderance of recently published evidence suggests benefits nearly exclusively in favor of catheter insertion using ultrasound guidance compared with electrical stimulation, although little new data are available to help guide practitioners regarding the specifics of ultrasound-guided catheter insertion (eg, optimal needle-nerve orientation). After some previous suggestions that automated, repeated bolus doses could provide benefits over a basal infusion, there is a dearth of supporting data published in the past few years. An increasing number of disposable infusion pumps does now allow a similar ability to adjust basal rates, bolus volume, and lockout times compared with their electronic, programmable counterparts, and a promising area of research is communicating with and controlling pumps remotely via the Internet. Large, prospective studies now document the relatively few major complications during ambulatory CPNB, although randomized, controlled studies demonstrating an actual shortening of hospitalization duration are few. Recent evidence suggests that, compared with femoral infusion, adductor canal catheters both induce less quadriceps femoris weakness and improve mobilization/ambulation, although the relative analgesia afforded by each remains in dispute. Newly published data demonstrate that the incidence and/or severity of chronic, persistent postsurgical pain may, at times, be decreased with a short-term postoperative CPNB. Few new CPNB-related complications have been identified, although large, prospective trials provide additional data regarding the incidence of adverse events. Lastly, a number of novel, alternative analgesic modalities are under development/investigation. Four such techniques are described and contrasted with CPNB, including single-injection peripheral nerve blocks with newer adjuvants, liposome bupivacaine used in wound infiltration and peripheral nerve blocks, cryoanalgesia with cryoneurolysis, and percutaneous peripheral nerve stimulation.

BackgroundIt remains unknown whether continuous or scheduled intermittent bolus local anesthetic administration is preferable for adductor canal perineural catheters. Therefore, we tested the hypothesis that scheduled bolus administration is superior or noninferior to a continuous infusion on cutaneous knee sensation in volunteers.MethodsBilateral adductor canal catheters were inserted in 24 volunteers followed by ropivacaine 0.2% administration for 8 hours. One limb of each subject was assigned randomly to a continuous infusion (8 mL/h) or automated hourly boluses (8 mL/bolus), with the alternate treatment in the contralateral limb. The primary end point was the tolerance to electrical current applied through cutaneous electrodes in the distribution of the anterior branch of the medial femoral cutaneous nerve after 8 hours (noninferiority delta: -10 mA). Secondary end points included tolerance of electrical current and quadriceps femoris maximum voluntary isometric contraction strength at baseline, hourly for 14 hours, and again after 22 hours.ResultsThe 2 administration techniques provided equivalent cutaneous analgesia at 8 hours because noninferiority was found in both directions, with estimated difference on tolerance to cutaneous current of -0.6 mA (95% confidence interval, -5.4 to 4.3). Equivalence also was found on all but 2 secondary time points.ConclusionsNo evidence was found to support the hypothesis that changing the local anesthetic administration technique (continuous basal versus hourly bolus) when using an adductor canal perineural catheter at 8 mL/h decreases cutaneous sensation in the distribution of the anterior branch of the medial femoral cutaneous nerve.

BackgroundIt remains unknown whether continuous or scheduled intermittent bolus local anesthetic administration is preferable for adductor canal perineural catheters. Therefore, we tested the hypothesis that scheduled bolus administration is superior or noninferior to a continuous infusion on cutaneous knee sensation in volunteers.MethodsBilateral adductor canal catheters were inserted in 24 volunteers followed by ropivacaine 0.2% administration for 8 hours. One limb of each subject was assigned randomly to a continuous infusion (8 mL/h) or automated hourly boluses (8 mL/bolus), with the alternate treatment in the contralateral limb. The primary end point was the tolerance to electrical current applied through cutaneous electrodes in the distribution of the anterior branch of the medial femoral cutaneous nerve after 8 hours (noninferiority delta: -10 mA). Secondary end points included tolerance of electrical current and quadriceps femoris maximum voluntary isometric contraction strength at baseline, hourly for 14 hours, and again after 22 hours.ResultsThe 2 administration techniques provided equivalent cutaneous analgesia at 8 hours because noninferiority was found in both directions, with estimated difference on tolerance to cutaneous current of -0.6 mA (95% confidence interval, -5.4 to 4.3). Equivalence also was found on all but 2 secondary time points.ConclusionsNo evidence was found to support the hypothesis that changing the local anesthetic administration technique (continuous basal versus hourly bolus) when using an adductor canal perineural catheter at 8 mL/h decreases cutaneous sensation in the distribution of the anterior branch of the medial femoral cutaneous nerve.

Fetal nicotine exposure increased risk of developing cardiovascular disease later in life. The present study tested the hypothesis that perinatal nicotine-induced programming of heart ischemia-sensitive phenotype is mediated by enhanced reactive oxygen species (ROS) in offspring. Nicotine was administered to pregnant rats via subcutaneous osmotic minipumps from day 4 of gestation to day 10 after birth, in the absence or presence of a ROS inhibitor, N-acetyl-cysteine (NAC) in drinking water. Experiments were conducted in 8 month old age male offspring. Isolated hearts were perfused in a Langendorff preparation. Perinatal nicotine treatment significantly increased ischemia and reperfusion-induced left ventricular injury, and decreased post-ischemic recovery of left ventricular function and coronary flow rate. In addition, nicotine enhanced cardiac ROS production and significantly attenuated protein kinase Cε (PKCε) protein abundance in the heart. Although nicotine had no effect on total cardiac glycogen synthase kinase-3β (GSK3β) protein expression, it significantly increased the phosphorylation of GSK3β at serine 9 residue in the heart. NAC inhibited nicotine-mediated increase in ROS production, recovered PKCε gene expression and abrogated increased phosphorylation of GSK3β. Of importance, NAC blocked perinatal nicotine-induced increase in ischemia and reperfusion injury in the heart. These findings provide novel evidence that increased oxidative stress plays a causal role in perinatal nicotine-induced developmental programming of ischemic sensitive phenotype in the heart, and suggest potential therapeutic targets of anti-oxidative stress in the treatment of ischemic heart disease.

Fetal nicotine exposure increased risk of developing cardiovascular disease later in life. The present study tested the hypothesis that perinatal nicotine-induced programming of heart ischemia-sensitive phenotype is mediated by enhanced reactive oxygen species (ROS) in offspring. Nicotine was administered to pregnant rats via subcutaneous osmotic minipumps from day 4 of gestation to day 10 after birth, in the absence or presence of a ROS inhibitor, N-acetyl-cysteine (NAC) in drinking water. Experiments were conducted in 8 month old age male offspring. Isolated hearts were perfused in a Langendorff preparation. Perinatal nicotine treatment significantly increased ischemia and reperfusion-induced left ventricular injury, and decreased post-ischemic recovery of left ventricular function and coronary flow rate. In addition, nicotine enhanced cardiac ROS production and significantly attenuated protein kinase Cε (PKCε) protein abundance in the heart. Although nicotine had no effect on total cardiac glycogen synthase kinase-3β (GSK3β) protein expression, it significantly increased the phosphorylation of GSK3β at serine 9 residue in the heart. NAC inhibited nicotine-mediated increase in ROS production, recovered PKCε gene expression and abrogated increased phosphorylation of GSK3β. Of importance, NAC blocked perinatal nicotine-induced increase in ischemia and reperfusion injury in the heart. These findings provide novel evidence that increased oxidative stress plays a causal role in perinatal nicotine-induced developmental programming of ischemic sensitive phenotype in the heart, and suggest potential therapeutic targets of anti-oxidative stress in the treatment of ischemic heart disease.

Effective treatment of glioblastoma (GBM) remains a formidable challenge. Survival rates remain poor despite decades of clinical trials of conventional and novel, biologically targeted therapeutics. There is considerable evidence that most of these therapeutics do not reach their targets in the brain when administered via conventional routes (intravenous or oral). Hence, direct delivery of therapeutics to the brain and to brain tumors is an active area of investigation. One of these techniques, convection-enhanced delivery (CED), involves the implantation of catheters through which conventional and novel therapeutic formulations can be delivered using continuous, low-positive-pressure bulk flow. Investigation in preclinical and clinical settings has demonstrated that CED can produce effective delivery of therapeutics to substantial volumes of brain and brain tumor. However, limitations in catheter technology and imaging of delivery have prevented this technique from being reliable and reproducible, and the only completed phase III study in GBM did not show a survival benefit for patients treated with an investigational therapeutic delivered via CED. Further development of CED is ongoing, with novel catheter designs and imaging approaches that may allow CED to become a more effective therapeutic delivery technique.

BackgroundIt remains unknown whether local anaesthetic dose is the only factor influencing continuous popliteal-sciatic nerve block effects, or whether concentration, volume, or both exert an influence as well.MethodsBilateral sciatic catheters were inserted in volunteers (n=24). Catheters were randomly assigned to ropivacaine of either 0.1% (8 ml h(-1)) or 0.4% (2 ml h(-1)) for 6 h. The primary endpoint was the tolerance to transcutaneous electrical stimulation within the tibial nerve distribution at hour 6. Secondary endpoints included current tolerance at other time points and plantar flexion maximum voluntary isometric contraction (22 h total).ResultsAt hour 6, tolerance to cutaneous stimulation for limbs receiving 0.1% ropivacaine was [mean (standard deviation)] 27.0 (20.2) vs26.9 (20.4) mA for limbs receiving 0.4% [estimated mean difference 0.2 mA; 90% confidence interval (CI) -8.2 to 8.5; P=0.02 and 0.03 for lower and upper boundaries, respectively]. Because the 90% CI fell within the prespecified tolerance ±10 mA, we conclude that the effect of the two concentration/volume combinations were equivalent. Similar negative findings were found for the secondary outcomes.ConclusionsFor continuous popliteal-sciatic nerve blocks, we found no evidence that local anaesthetic concentration and volume influence block characteristics, suggesting that local anaesthetic dose (mass) is the primary determinant of perineural infusion effects in this anatomic location. These findings suggest that for ambulatory perineural local anaesthetic infusion-for which there is usually a finite local anaesthetic reservoir-decreasing the basal rate while increasing the local anaesthetic concentration may allow for increased infusion duration without compromising postoperative analgesia.Clinical trial registrationNCT01898689.

UnlabelledMigalastat HCl (AT1001, 1-Deoxygalactonojirimycin) is an investigational pharmacological chaperone for the treatment of α-galactosidase A (α-Gal A) deficiency, which leads to Fabry disease, an X-linked, lysosomal storage disorder. The currently approved, biologics-based therapy for Fabry disease is enzyme replacement therapy (ERT) with either agalsidase alfa (Replagal) or agalsidase beta (Fabrazyme). Based on preclinical data, migalastat HCl in combination with agalsidase is expected to result in the pharmacokinetic (PK) enhancement of agalsidase in plasma by increasing the systemic exposure of active agalsidase, thereby leading to increased cellular levels in disease-relevant tissues. This Phase 2a study design consisted of an open-label, fixed-treatment sequence that evaluated the effects of single oral doses of 150 mg or 450 mg migalastat HCl on the PK and tissue levels of intravenously infused agalsidase (0.2, 0.5, or 1.0 mg/kg) in male Fabry patients. As expected, intravenous administration of agalsidase alone resulted in increased α-Gal A activity in plasma, skin, and peripheral blood mononuclear cells (PBMCs) compared to baseline. Following co-administration of migalastat HCl and agalsidase, α-Gal A activity in plasma was further significantly increased 1.2- to 5.1-fold compared to agalsidase administration alone, in 22 of 23 patients (95.6%). Importantly, similar increases in skin and PBMC α-Gal A activity were seen following co-administration of migalastat HCl and agalsidase. The effects were not related to the administered migalastat HCl dose, as the 150 mg dose of migalastat HCl increased α-Gal A activity to the same extent as the 450 mg dose. Conversely, agalsidase had no effect on the plasma PK of migalastat. No migalastat HCl-related adverse events or drug-related tolerability issues were identified.Trial registrationClinicalTrials.gov NCT01196871.

BackgroundIt remains unknown whether local anaesthetic dose is the only factor influencing continuous popliteal-sciatic nerve block effects, or whether concentration, volume, or both exert an influence as well.MethodsBilateral sciatic catheters were inserted in volunteers (n=24). Catheters were randomly assigned to ropivacaine of either 0.1% (8 ml h(-1)) or 0.4% (2 ml h(-1)) for 6 h. The primary endpoint was the tolerance to transcutaneous electrical stimulation within the tibial nerve distribution at hour 6. Secondary endpoints included current tolerance at other time points and plantar flexion maximum voluntary isometric contraction (22 h total).ResultsAt hour 6, tolerance to cutaneous stimulation for limbs receiving 0.1% ropivacaine was [mean (standard deviation)] 27.0 (20.2) vs26.9 (20.4) mA for limbs receiving 0.4% [estimated mean difference 0.2 mA; 90% confidence interval (CI) -8.2 to 8.5; P=0.02 and 0.03 for lower and upper boundaries, respectively]. Because the 90% CI fell within the prespecified tolerance ±10 mA, we conclude that the effect of the two concentration/volume combinations were equivalent. Similar negative findings were found for the secondary outcomes.ConclusionsFor continuous popliteal-sciatic nerve blocks, we found no evidence that local anaesthetic concentration and volume influence block characteristics, suggesting that local anaesthetic dose (mass) is the primary determinant of perineural infusion effects in this anatomic location. These findings suggest that for ambulatory perineural local anaesthetic infusion-for which there is usually a finite local anaesthetic reservoir-decreasing the basal rate while increasing the local anaesthetic concentration may allow for increased infusion duration without compromising postoperative analgesia.Clinical trial registrationNCT01898689.

UnlabelledMigalastat HCl (AT1001, 1-Deoxygalactonojirimycin) is an investigational pharmacological chaperone for the treatment of α-galactosidase A (α-Gal A) deficiency, which leads to Fabry disease, an X-linked, lysosomal storage disorder. The currently approved, biologics-based therapy for Fabry disease is enzyme replacement therapy (ERT) with either agalsidase alfa (Replagal) or agalsidase beta (Fabrazyme). Based on preclinical data, migalastat HCl in combination with agalsidase is expected to result in the pharmacokinetic (PK) enhancement of agalsidase in plasma by increasing the systemic exposure of active agalsidase, thereby leading to increased cellular levels in disease-relevant tissues. This Phase 2a study design consisted of an open-label, fixed-treatment sequence that evaluated the effects of single oral doses of 150 mg or 450 mg migalastat HCl on the PK and tissue levels of intravenously infused agalsidase (0.2, 0.5, or 1.0 mg/kg) in male Fabry patients. As expected, intravenous administration of agalsidase alone resulted in increased α-Gal A activity in plasma, skin, and peripheral blood mononuclear cells (PBMCs) compared to baseline. Following co-administration of migalastat HCl and agalsidase, α-Gal A activity in plasma was further significantly increased 1.2- to 5.1-fold compared to agalsidase administration alone, in 22 of 23 patients (95.6%). Importantly, similar increases in skin and PBMC α-Gal A activity were seen following co-administration of migalastat HCl and agalsidase. The effects were not related to the administered migalastat HCl dose, as the 150 mg dose of migalastat HCl increased α-Gal A activity to the same extent as the 450 mg dose. Conversely, agalsidase had no effect on the plasma PK of migalastat. No migalastat HCl-related adverse events or drug-related tolerability issues were identified.Trial registrationClinicalTrials.gov NCT01196871.

BackgroundSingle-injection transversus abdominis plane (TAP) block provides postoperative analgesia and decreases supplemental analgesic requirements. However, there is currently no evidence from randomized, controlled studies investigating the possible benefits of continuous TAP blocks. Therefore, the aim of this randomized, triple-masked, placebo-controlled study was to determine if benefits are afforded by adding a multiple-day, ambulatory, continuous ropivacaine TAP block to a single-injection block following hernia surgery.MethodsPreoperatively, subjects undergoing unilateral inguinal (N=19) or peri-umbilical (N=1) hernia surgery received unilateral or bilateral TAP perineural catheter(s), respectively. All received a ropivacaine 0.5% (20 mL) bolus via the catheter(s). Subjects were randomized to either postoperative perineural ropivacaine 0.2% or normal saline using portable infusion pump(s). Subjects were discharged home where the catheter(s) were removed the evening of postoperative day (POD) 2. Subjects were contacted on POD 0-3. The primary endpoint was average pain with movement (scale: 0-10) queried on POD 1.ResultsTwenty subjects of a target 30 were enrolled due to the primary surgeon's unanticipated departure from the institution. Average pain queried on POD 1 for subjects receiving ropivacaine (N=10) was a mean (standard deviation) of 3.0 (2.6) vs 2.8 (2.7) for subjects receiving saline (N=10; 95% confidence interval difference in means -2.9 to 3.4; P=0.86). There were no statistically significant differences detected between treatment groups in any secondary endpoint.ConclusionsThe results of this study do not support adding an ambulatory, continuous ropivacaine infusion to a single-injection ropivacaine TAP block for hernia surgery. However, the present investigation was underpowered, and further study is warranted.

BackgroundSingle-injection transversus abdominis plane (TAP) block provides postoperative analgesia and decreases supplemental analgesic requirements. However, there is currently no evidence from randomized, controlled studies investigating the possible benefits of continuous TAP blocks. Therefore, the aim of this randomized, triple-masked, placebo-controlled study was to determine if benefits are afforded by adding a multiple-day, ambulatory, continuous ropivacaine TAP block to a single-injection block following hernia surgery.MethodsPreoperatively, subjects undergoing unilateral inguinal (N=19) or peri-umbilical (N=1) hernia surgery received unilateral or bilateral TAP perineural catheter(s), respectively. All received a ropivacaine 0.5% (20 mL) bolus via the catheter(s). Subjects were randomized to either postoperative perineural ropivacaine 0.2% or normal saline using portable infusion pump(s). Subjects were discharged home where the catheter(s) were removed the evening of postoperative day (POD) 2. Subjects were contacted on POD 0-3. The primary endpoint was average pain with movement (scale: 0-10) queried on POD 1.ResultsTwenty subjects of a target 30 were enrolled due to the primary surgeon's unanticipated departure from the institution. Average pain queried on POD 1 for subjects receiving ropivacaine (N=10) was a mean (standard deviation) of 3.0 (2.6) vs 2.8 (2.7) for subjects receiving saline (N=10; 95% confidence interval difference in means -2.9 to 3.4; P=0.86). There were no statistically significant differences detected between treatment groups in any secondary endpoint.ConclusionsThe results of this study do not support adding an ambulatory, continuous ropivacaine infusion to a single-injection ropivacaine TAP block for hernia surgery. However, the present investigation was underpowered, and further study is warranted.

Intrathecal drug delivery systems are becoming an increasingly common modality used by physicians to treat patients. Specifically, chronic spasticity secondary to multiple sclerosis (MS) may be treated with intrathecal baclofen (ITB) therapy when oral antispasmodics do not provide adequate relief. ITB therapy is effective, localizes drug delivery, and does not have the same degree of intolerable systemic effects often seen with oral and parenteral medications. As the use of intrathecal drug delivery systems has become more common, so has the incidence of adverse events. ITB administration requires the surgical implantation of indwelling catheters and a pump reservoir. Although this therapy is useful in treating spasticity, risks unique to intrathecal drug delivery systems include medication dosing errors, pump malfunction, infection, and catheter breakage or dislocation. To our knowledge intrathecal pump catheter migration into the spinal cord is a very rare complication with only 2 such complications reported. We present a case of an intrathecal baclofen pump catheter that was initially believed to have migrated into the spinal cord and the innovative use of cinefluoroscopy and digital subtraction used to identify catheter placement. Moreover, after confirmation of the catheter position within the spinal cord on magnetic resonance imaging (MRI) our team elected to perform a laminectomy, which demonstrated that the catheter was not in the spinal cord but was surrounded by arachnoid adhesions. We hope our efforts will provide the clinician insight into the common difficulties that arise and how best to troubleshoot them to serve this specific patient population and prevent potentially life-threatening complications.

Endothelial dysfunction is a common early pathogenic event in patients with type 2 diabetes (T2D) who exhibit cardiovascular disease. In the present study, we have examined the effect of SKA-31, a positive modulator of endothelial Ca(2+)-activated K(+) (KCa) channels, on total coronary flow in isolated hearts from Goto-Kakizaki rats, a non-obese model of T2D exhibiting metabolic syndrome. Total coronary flow and left ventricular developed pressure were monitored simultaneously in isolated, spontaneously beating Langendorff-perfused hearts. Acute administrations of bradykinin (BK) or adenosine (ADO) increased coronary flow, but responses were significantly blunted in diabetic hearts at 10-12 and 18-20weeks of age compared with age-matched Wistar controls, consistent with the presence of endothelial dysfunction. In contrast, SKA-31 dose-dependently (0.01-5μg) increased total coronary flow to comparable levels in both control and diabetic rat hearts at both ages. Flow responses to sodium nitroprusside were not different between control and diabetic hearts, suggesting normal arterial smooth muscle function. Importantly, exposure to a sub-threshold concentration of SKA-31 (i.e. 0.3μM) rescued the impaired BK and ADO-evoked vasodilatory responses in diabetic hearts. Endothelial KCa channel activators may thus help to preserve coronary flow in diabetic myocardium.

Endothelial dysfunction is a common early pathogenic event in patients with type 2 diabetes (T2D) who exhibit cardiovascular disease. In the present study, we have examined the effect of SKA-31, a positive modulator of endothelial Ca(2+)-activated K(+) (KCa) channels, on total coronary flow in isolated hearts from Goto-Kakizaki rats, a non-obese model of T2D exhibiting metabolic syndrome. Total coronary flow and left ventricular developed pressure were monitored simultaneously in isolated, spontaneously beating Langendorff-perfused hearts. Acute administrations of bradykinin (BK) or adenosine (ADO) increased coronary flow, but responses were significantly blunted in diabetic hearts at 10-12 and 18-20weeks of age compared with age-matched Wistar controls, consistent with the presence of endothelial dysfunction. In contrast, SKA-31 dose-dependently (0.01-5μg) increased total coronary flow to comparable levels in both control and diabetic rat hearts at both ages. Flow responses to sodium nitroprusside were not different between control and diabetic hearts, suggesting normal arterial smooth muscle function. Importantly, exposure to a sub-threshold concentration of SKA-31 (i.e. 0.3μM) rescued the impaired BK and ADO-evoked vasodilatory responses in diabetic hearts. Endothelial KCa channel activators may thus help to preserve coronary flow in diabetic myocardium.

BackgroundWe aimed to determine with this randomized, triple-masked, placebo-controlled study if benefits are afforded by adding a multiple-day, ambulatory, continuous ropivacaine paravertebral nerve block to a single-injection ropivacaine paravertebral block after mastectomy.MethodsPreoperatively, 60 subjects undergoing unilateral (n = 24) or bilateral (n = 36) mastectomy received either unilateral or bilateral paravertebral perineural catheter(s), respectively, inserted between the third and fourth thoracic transverse process(es). All subjects received an initial bolus of ropivacaine 0.5% (15 mL) via the catheter(s). Subjects were randomized to receive either perineural ropivacaine 0.4% or normal saline using portable infusion pump(s) [5 mL/h basal; 300 mL reservoir(s)]. Subjects remained hospitalized for at least 1 night and were subsequently discharged home where the catheter(s) were removed on postoperative day (POD) 3. Subjects were contacted by telephone on PODs 1, 4, 8, and 28. The primary end point was average pain (scale, 0-10) queried on POD 1.ResultsAverage pain queried on POD 1 for subjects receiving perineural ropivacaine (n = 30) was a median (interquartile) of 2 (0-3), compared with 4 (1-5) for subjects receiving saline (n = 30; 95% confidence interval difference in medians, -4.0 to -0.3; P = 0.021]. During this same period, subjects receiving ropivacaine experienced a lower severity of breakthrough pain (5 [3-6] vs 7 [5-8]; P = 0.046) as well. As a result, subjects receiving perineural ropivacaine experienced less pain-induced physical and emotional dysfunction, as measured with the Brief Pain Inventory (lower score = less dysfunction): 14 (4-37) versus 57 (8-67) for subjects receiving perineural saline (P = 0.012). For the subscale that measures the degree of interference of pain on 7 domains, such as general activity and relationships, subjects receiving perineural saline reported a median score 10 times higher (more dysfunction) than those receiving ropivacaine (3 [0-24] vs 33 [0-44]; P = 0.035). In contrast, after infusion discontinuation, there were no statistically significant differences detected between treatment groups.ConclusionsAfter mastectomy, adding a multiple-day, ambulatory, continuous ropivacaine infusion to a single-injection ropivacaine paravertebral nerve block results in improved analgesia and less functional deficit during the infusion. However, no benefits were identified after infusion discontinuation.

We report a new method to display the minute fluctuations induced by syringe pumps on microfluidic flows by using a liquid-liquid system with an ultralow interfacial tension. We demonstrate that the stepper motor inside the pump is a source of fluctuations in microfluidic flows by comparing the frequencies of the ripples observed at the interface to that of the pulsation of the stepper motor. We also quantify the fluctuations induced at different flow rates, using syringes of different diameters, and using different syringe pumps with different advancing distances per step. Our work provides a way to predict the frequency of the fluctuation that the driving syringe pump induces on a microfluidic system and suggests that syringe pumps can be a source of fluctuations in microfluidic flows, thus contributing to the polydispersity of the resulting droplets.

We report a new method to display the minute fluctuations induced by syringe pumps on microfluidic flows by using a liquid-liquid system with an ultralow interfacial tension. We demonstrate that the stepper motor inside the pump is a source of fluctuations in microfluidic flows by comparing the frequencies of the ripples observed at the interface to that of the pulsation of the stepper motor. We also quantify the fluctuations induced at different flow rates, using syringes of different diameters, and using different syringe pumps with different advancing distances per step. Our work provides a way to predict the frequency of the fluctuation that the driving syringe pump induces on a microfluidic system and suggests that syringe pumps can be a source of fluctuations in microfluidic flows, thus contributing to the polydispersity of the resulting droplets.

BackgroundWe aimed to determine with this randomized, triple-masked, placebo-controlled study if benefits are afforded by adding a multiple-day, ambulatory, continuous ropivacaine paravertebral nerve block to a single-injection ropivacaine paravertebral block after mastectomy.MethodsPreoperatively, 60 subjects undergoing unilateral (n = 24) or bilateral (n = 36) mastectomy received either unilateral or bilateral paravertebral perineural catheter(s), respectively, inserted between the third and fourth thoracic transverse process(es). All subjects received an initial bolus of ropivacaine 0.5% (15 mL) via the catheter(s). Subjects were randomized to receive either perineural ropivacaine 0.4% or normal saline using portable infusion pump(s) [5 mL/h basal; 300 mL reservoir(s)]. Subjects remained hospitalized for at least 1 night and were subsequently discharged home where the catheter(s) were removed on postoperative day (POD) 3. Subjects were contacted by telephone on PODs 1, 4, 8, and 28. The primary end point was average pain (scale, 0-10) queried on POD 1.ResultsAverage pain queried on POD 1 for subjects receiving perineural ropivacaine (n = 30) was a median (interquartile) of 2 (0-3), compared with 4 (1-5) for subjects receiving saline (n = 30; 95% confidence interval difference in medians, -4.0 to -0.3; P = 0.021]. During this same period, subjects receiving ropivacaine experienced a lower severity of breakthrough pain (5 [3-6] vs 7 [5-8]; P = 0.046) as well. As a result, subjects receiving perineural ropivacaine experienced less pain-induced physical and emotional dysfunction, as measured with the Brief Pain Inventory (lower score = less dysfunction): 14 (4-37) versus 57 (8-67) for subjects receiving perineural saline (P = 0.012). For the subscale that measures the degree of interference of pain on 7 domains, such as general activity and relationships, subjects receiving perineural saline reported a median score 10 times higher (more dysfunction) than those receiving ropivacaine (3 [0-24] vs 33 [0-44]; P = 0.035). In contrast, after infusion discontinuation, there were no statistically significant differences detected between treatment groups.ConclusionsAfter mastectomy, adding a multiple-day, ambulatory, continuous ropivacaine infusion to a single-injection ropivacaine paravertebral nerve block results in improved analgesia and less functional deficit during the infusion. However, no benefits were identified after infusion discontinuation.

BackgroundThe authors tested the hypotheses that, compared with an overnight continuous femoral nerve block (cFNB), a 4-day ambulatory cFNB increases ambulation distance and decreases the time until three specific readiness-for-discharge criteria are met after tricompartment total knee arthroplasty.MethodsPreoperatively, all patients received a cFNB (n = 50) and perineural ropivacaine 0.2% from surgery until the following morning, at which time they were randomly assigned to either continue perineural ropivacaine or switch to perineural normal saline. Primary endpoints included (1) time to attain three discharge criteria (adequate analgesia, independence from intravenous analgesics, and ambulation of at least 30 m) and (2) ambulatory distance in 6 min the afternoon after surgery. Patients were discharged with their cFNB and a portable infusion pump, and catheters were removed on postoperative day 4.ResultsPatients given 4 days of perineural ropivacaine attained all three discharge criteria in a median (25th-75th percentiles) of 25 (21-47) h, compared with 71 (46-89) h for those of the control group (estimated ratio, 0.47; 95% confidence interval, 0.32-0.67; P

BackgroundThe authors tested the hypotheses that, compared with an overnight continuous femoral nerve block (cFNB), a 4-day ambulatory cFNB increases ambulation distance and decreases the time until three specific readiness-for-discharge criteria are met after tricompartment total knee arthroplasty.MethodsPreoperatively, all patients received a cFNB (n = 50) and perineural ropivacaine 0.2% from surgery until the following morning, at which time they were randomly assigned to either continue perineural ropivacaine or switch to perineural normal saline. Primary endpoints included (1) time to attain three discharge criteria (adequate analgesia, independence from intravenous analgesics, and ambulation of at least 30 m) and (2) ambulatory distance in 6 min the afternoon after surgery. Patients were discharged with their cFNB and a portable infusion pump, and catheters were removed on postoperative day 4.ResultsPatients given 4 days of perineural ropivacaine attained all three discharge criteria in a median (25th-75th percentiles) of 25 (21-47) h, compared with 71 (46-89) h for those of the control group (estimated ratio, 0.47; 95% confidence interval, 0.32-0.67; P

BACKGROUND AND OBJECTIVES:Ambulatory perineural local anesthetic infusion is a relatively new method for providing postoperative analgesia, and many aspects of this technique remain in the domain of conjecture and speculation. This retrospective chart review and survey was undertaken to investigate patients' opinions on various aspects of their ambulatory perineural infusion experience. METHODS:Patients who had received an ambulatory perineural infusion from the University of Florida were identified via pharmacy records. Patients were contacted by phone and were asked various questions regarding their experiences and preferences during and after their perineural infusion. RESULTS:Of 217 patients identified, 215 charts were located and retrieved. Of these, 137 (64%) were successfully contacted and 131 (61%) consented to take part in the survey. More than 97% of patients reported that they felt "safe" during home infusion, that one physician telephone call each night was optimal contact, and that they were comfortable removing the catheter with instructions given over the phone. Only 4% would have preferred to return for catheter removal, and 43% felt that they would have been comfortable with only written instructions for catheter removal. CONCLUSION:This investigation suggests that perineural local anesthetic infusion is generally well tolerated by ambulatory patients.

BACKGROUND AND OBJECTIVES:Ambulatory perineural local anesthetic infusion is a relatively new method for providing postoperative analgesia, and many aspects of this technique remain in the domain of conjecture and speculation. This retrospective chart review and survey was undertaken to investigate patients' opinions on various aspects of their ambulatory perineural infusion experience. METHODS:Patients who had received an ambulatory perineural infusion from the University of Florida were identified via pharmacy records. Patients were contacted by phone and were asked various questions regarding their experiences and preferences during and after their perineural infusion. RESULTS:Of 217 patients identified, 215 charts were located and retrieved. Of these, 137 (64%) were successfully contacted and 131 (61%) consented to take part in the survey. More than 97% of patients reported that they felt "safe" during home infusion, that one physician telephone call each night was optimal contact, and that they were comfortable removing the catheter with instructions given over the phone. Only 4% would have preferred to return for catheter removal, and 43% felt that they would have been comfortable with only written instructions for catheter removal. CONCLUSION:This investigation suggests that perineural local anesthetic infusion is generally well tolerated by ambulatory patients.

Background and objectivesLocal anesthetics infused via perineural catheters postoperatively decrease opioid use and side effects while improving analgesia. However, the infusion pumps described for outpatients have been limited by several factors, including the following: limited local anesthetic reservoir volume, fixed infusion rate, and inability to provide patient-controlled doses of local anesthetic in combination with a continuous infusion. We describe a patient undergoing open rotator cuff repair who was discharged home with an interscalene perineural catheter and a mechanical infusion pump that allowed a variable rate of continuous infusion, as well as patient-controlled boluses of local anesthetic for over 4 days.Case reportA 77-year-old woman, who had previously required a 3-day hospital admission for acute postoperative pain following an open repair of her left rotator cuff, presented for an open repair of her contralateral rotator cuff. Preoperatively she received an interscalene block and perineural catheter. After the procedure she was discharged home with a portable pump that infused ropivacaine continuously at a rate of 6 mL/h and allowed a 2-mL patient-controlled bolus every 20 minutes (550-mL reservoir). The basal infusion was decreased, as tolerated, by having the patient reprogram the pump with instructions given over the telephone. Without the use of any oral opioids, the patient scored her surgical pain 0 to 1 (on a scale of 0 to 10) while at rest and 2 to 3 for 2 physical therapy sessions during which she used the bolus function to reinforce her analgesia. After 98 hours of infusion, the patient's husband removed the catheter with instructions given over the telephone, and her subsequent surgical pain was treated with oral opioids.ConclusionContinuous, perineural local anesthetic infusions are possible on an ambulatory basis for multiple days using a portable, programmable pump that provides a variable basal infusion rate, patient-controlled boluses, and a large anesthetic reservoir.

Background and objectivesLocal anesthetics infused via perineural catheters postoperatively decrease opioid use and side effects while improving analgesia. However, the infusion pumps described for outpatients have been limited by several factors, including the following: limited local anesthetic reservoir volume, fixed infusion rate, and inability to provide patient-controlled doses of local anesthetic in combination with a continuous infusion. We describe a patient undergoing open rotator cuff repair who was discharged home with an interscalene perineural catheter and a mechanical infusion pump that allowed a variable rate of continuous infusion, as well as patient-controlled boluses of local anesthetic for over 4 days.Case reportA 77-year-old woman, who had previously required a 3-day hospital admission for acute postoperative pain following an open repair of her left rotator cuff, presented for an open repair of her contralateral rotator cuff. Preoperatively she received an interscalene block and perineural catheter. After the procedure she was discharged home with a portable pump that infused ropivacaine continuously at a rate of 6 mL/h and allowed a 2-mL patient-controlled bolus every 20 minutes (550-mL reservoir). The basal infusion was decreased, as tolerated, by having the patient reprogram the pump with instructions given over the telephone. Without the use of any oral opioids, the patient scored her surgical pain 0 to 1 (on a scale of 0 to 10) while at rest and 2 to 3 for 2 physical therapy sessions during which she used the bolus function to reinforce her analgesia. After 98 hours of infusion, the patient's husband removed the catheter with instructions given over the telephone, and her subsequent surgical pain was treated with oral opioids.ConclusionContinuous, perineural local anesthetic infusions are possible on an ambulatory basis for multiple days using a portable, programmable pump that provides a variable basal infusion rate, patient-controlled boluses, and a large anesthetic reservoir.