Programmable Infusion Pump Research Articles

Minimally invasive nasal infusion (MINI) approach for CNS delivery of protein therapeutics: A case study with ovalbumin

One of the primary obstacles in treating central nervous system (CNS) disorders lies in the limited ability of disease-modifying drugs to cross the blood-brain barrier (BBB). Our previously described Minimally Invasive Nasal Depot (MIND) technique has proven successful in delivering various drugs to the brain in rat models via a trans-olfactory mucosal approach. In this study, we introduce a novel Minimally Invasive Nasal Infusion (MINI) delivery approach for administering ovalbumin, a model protein, utilizing a programmable infusion pump (iPRECIO SMP-310R) in a mouse model. This research highlights the significant role of olfactory mucosa in nose-to-brain delivery, with an efficacy of nearly 45% compared to intracerebroventricular (ICV) administration. This demonstrates its potential as an alternative procedure for treating CNS diseases, offering a greater safety profile relative to the highly invasive clinical routes traditionally adopted for CNS drug delivery.

Circadian Clock Genes Are Regulated by Rhythmic Corticosterone at Physiological Levels in the Rat Hippocampus

Plain Language SummaryAll mammals, including humans, have an internal 24 h biological clock enabling us to synchronize and optimize our physiology to daily life. The 24 h circadian clock of body is localized in neurons of the suprachiasmatic nucleus (SCN) located in the hypothalamus of the brain and is characterized by rhythmic activity of special clock genes. Circadian 24 h rhythms are present throughout the brain, including the hippocampus, where clock genes seem to be important for memory and mood. However, the signaling mechanism controlling circadian clock gene rhythms in the hippocampus is unknown. We hypothesized that oscillations of clock genes in the hippocampus could be driven by a well-established SCN-controlled circadian rhythm in glucocorticoid hormones from the adrenal glands, known as stress hormone or cortisol in humans and corticosterone in rodents. To test this hypothesis, we generated a rat surgical animal model, in which the SCN and adrenal glands were removed and a 24 h exogenous corticosterone rhythm at normal physiological levels was reestablished by use of an implanted programmable infusion pump. Removal of the SCN efficiently abolished clock gene rhythms in the hippocampus; however, reintroducing the natural glucocorticoid rhythm led to reestablishment of 24 h activity rhythms in hippocampal clock genes. Thus, our data suggest that rhythmic hormone release from the adrenal glands drives hippocampal clock gene rhythms and therefore provides a dynamic 24 h hormonal link between the circadian clock of the SCN and circadian function of the hippocampus.

Understanding the effects of opioids vs non-opioids in the treatment of neonatal abstinence syndrome, an in vitro model.

Neonatal abstinence syndrome (NAS) refers to cadre of withdrawal manifestations in infants born to mothers who used illicit and licit substances during pregnancy. The increasing prevalence of NAS has been largely due to the maternal use of opioids during pregnancy. NAS contributes to increased morbidity and long-term disability in surviving infants. Clinically, oral opioid therapies for opioid exposure have been a standard treatment with morphine (MO) being the most commonly used medication. Recently, a non-opioid agent, clonidine (CD) has also been used with potentially favorable short- and long-term outcomes in infants. However, data regarding the cellular and molecular effects of these treatments on the developing brain is still lacking due to a lack of a reliable animal model that targets the neonatal brain. To address this gap in knowledge we determined the effects of MO or CD on the cell death of neonatal cortical explant cultures that were exposed to oxycodone (OXY) in utero. Sprague Dawley rats were randomized and implanted with programmable infusion pumps before mating to receive either the OXY (dose increasing from 1.21-1.90 mg/kg/day to a maximum dose of 2.86-3.49 mg/kg/day) or normal saline (NS) throughout pregnancy and until one week after delivery. Male and female rat pups were sacrificed on postnatal day 4, and the prefrontal cortex (PFC) and hippocampus (HC) were dissected and treated with MO (0.10-1.00 µM) or CD (1.20-120.00 µM) in culture media. After 5 days of treatment the explants were labeled with propidium iodide to detect cell death. Dead cells were analyzed and counted under fluorescence microscopy. In explants from the PFC, cell death was greater in those prenatally exposed to OXY and postnatally treated with MO (OXY/MO) (736.8 ± 76.5) compared to OXY/CD (620.9 ± 75.0; p = 0.005). In the HC explants, mean cell death counts were not significantly different between groups regardless of prenatal exposure or postnatal treatment (p = 0.19). The PFC is vital in controlling higher-order executive functions such as behavioral flexibility, learning and working memory. Therefore, our finding is consistent with executive function problems in children with prenatal opioid exposure.

Low-cost, programmable infusion pump with bolus mode for in-vivo imaging

Syringe pumps are routinely used in biomedical imaging laboratories for delivering contrast agents and either infusing or injecting a precise amount of liquids. Commercial syringe pumps that are developed by specialized companies are expensive and only have standard functions, which often do not meet the requirements of individual experiments. In this paper, we demonstrate an open–source single syringe pump with the possibility of adapting to the needs of a researcher. The device that was designed, is controlled by an Arduino Leonardo, along with the stepper motor driver. For sending commands and receiving the current plunger position, a C# software was developed with serial communication via USB. Additionally, the 3D models were made in a universal way, which allows for the use of any syringe size. An example of the application of the syringe pump for biomedical applications was demonstrated using electron resonance imaging (ERI). The single syringe pump tests were demonstrated by simulating the filling of a particular volume inside the resonator. This example reflects the clearance process after an intravascular (I.V) drug administration in the murine model. The experiments were performed on an ERI TM 600 tomograph. The results confirmed that the designed syringe pump allowed for controlling the infusion speed and injected volume. Moreover, we present a user-friendly and open-source graphical interface that is a low-cost alternative for commercial devices.

Reduced Sensitivity to Anesthetic Agents upon Lesioning the Mesopontine Tegmental Anesthesia Area in Rats Depends on Anesthetic Type.

The brainstem mesopontine tegmental anesthesia area is a key node in circuitry responsible for anesthetic induction and maintenance. Microinjecting the γ-aminobutyric acid-mediated (GABAergic) anesthetic pentobarbital in this nucleus rapidly and reversibly induces general anesthesia, whereas lesioning it renders the animal relatively insensitive to pentobarbital administered systemically. This study investigated whether effects of lesioning the mesopontine tegmental anesthesia area generalize to other anesthetic agents. Cell-selective lesions were made using ibotenic acid, and rats were later tested for changes in the dose-response relation to etomidate, propofol, alfaxalone/alfadolone, ketamine, and medetomidine delivered intravenously using a programmable infusion pump. Anesthetic induction for each agent was tracked using five behavioral endpoints: loss of righting reflex, criterion for anesthesia (score of 11 or higher), criterion for surgical anesthesia (score of 14 or higher), antinociception (loss of pinch response), and deep surgical anesthesia (score of 16). As reported previously for pentobarbital, on-target mesopontine tegmental anesthesia area lesions reduced sensitivity to the GABAergic anesthetics etomidate and propofol. The dose to achieve a score of 16 increased to 147 ± 50% of baseline in control animals ± SD (P = 0.0007; 7 lesioned rats and 18 controls) and 136 ± 58% of baseline (P = 0.010; 6 lesioned rats and 21 controls), respectively. In contrast, responsiveness to the neurosteroids alfaxalone and alfadolone remained unchanged compared with baseline (94 ± 24%; P = 0.519; 6 lesioned rats and 18 controls) and with ketamine increased slightly (90 ± 11%; P = 0.039; 6 lesioned rats and 19 controls). The non-GABAergic anesthetic medetomidine did not induce criterion anesthesia even at the maximal dose tested. The dose to reach the maximal anesthesia score actually obtained was unaffected by the lesion (112 ± 8%; P = 0.063; 5 lesioned rats and 18 controls). Inability to induce anesthesia in lesioned animals using normally effective doses of etomidate, propofol, and pentobarbital suggests that the mesopontine tegmental anesthesia area is the effective target of these, but not necessarily all, GABAergic anesthetics upon systemic administration. Cortical and spinal functions are likely suppressed by recruitment of dedicated ascending and descending pathways rather than by direct, distributed drug action.

Accuracy and Precision of the SynchroMed II Pump

The objective of this study was to evaluate the accuracy and precision of SynchroMed II programmable infusion pumps for delivery of intrathecal baclofen to treat severe spasticity. Retrospective chart review study. Urban academic rehabilitation clinic. Patients with spasticity treated with intrathecal baclofen. A retrospective chart review of 149 patients inclusive of 755 individual patient encounters more than a 2.5-year span for baclofen pump refills was performed. Charts were reviewed to obtain data on the concentration and dose of intrathecal baclofen, aspirated and residual volumes, age of the pump, and reservoir volume of the pump. Flow rate (mL/day) was calculated for each chronological visit. Flow rates from clinical data were used to calculate the accuracy and precision based on the manufacturer's specifications for both the 20 mL and 40 mL pumps. The infused volume accuracy and precision of both the 20 mL pumps and 40 mL pumps remained within manufacturer's specifications while delivering drug at a rate slightly lower than predicted. There were no cases of pump over-infusion. There is a statistically significant decrease in flow rate accuracy over the lifespan of the pump. SynchroMed II pumps infuse at slightly less than their predicted rate while remaining within the manufacturer's specifications. No pump over-infusions were noted. Pump flow rate declines over time. Further study is warranted to assess the impact of this flow rate decrease on patient treatment and safety.

An audit of propofol administration in the intensive care unit: Infusion pump–recorded versus electronically documented amounts

BackgroundAlthough propofol is widely used for sedation in intensive care units around Australia, evaluation of bedside nursing practices of the administration of propofol have been limited. We investigated whether there was a discrepancy between the amount of propofol delivered by the infusion pump and that recorded electronically and consequently patient exposure to avoidable harms. AimsThe aim of this research was to compare the total amount of propofol administered to intensive care patients via a programmable infusion pump with that documented in the electronic medical record (EMR). Secondary objectives were to ascertain the percentage of 1) patients exposed to a propofol dose greater than recommended and 2) daily energy requirements administered as propofol infusion. MethodsThis was a prospective, observational study of total propofol delivered to 50 patients in a 14-bed metropolitan, Australian intensive care unit. Infusion pump data and entries from the EMR were collated. ResultsPropofol sedation was administered for a median 18 (interquartile range: 14–47) hours with median total propofol 3025 mg (interquartile range: 1840–7755 mg) by pump and 3250 mg (interquartile range: 1915–6960 mg) by EMR, i.e. 1.9 (interquartile range: 1.3–2.3) mg/kg/hour by pump (correlation coefficient = 0.99). The total bolus propofol documented in the EMR was a median 330 mg (interquartile range: −838 to −124) less than the pump amount. Nineteen (38%) patients had no EMR-documented propofol boluses yet had received at least one bolus via the pump. In two of 50 (4%) patients, the pump propofol infusion dose was above the recommended maximum safe dose of 4 mg/kg/h. ConclusionIn this cohort of patients, the bolus administration of propofol was frequently not documented, potentially placing some patients at risk of drug-related toxicity. Further research to develop and implement strategies to improve the documentation of propofol administration is indicated.

Systematic patient involvement for homebased outpatient administration of complex chemotherapy in acute leukemia and lymphoma.

Based on experience with comprehensive patient involvement, we present data from implementation of portable, programmable infusion pumps (PPP) for home-based chemotherapy administration in patients with acute leukaemia and in lymphoma patients receiving (carmustine, etoposide, cytarabine, melphalan) BEAM regimen. Data from 84 patients, receiving 177 cycles of PPP administered chemotherapy, showed convincing safety with minor equipment errors encountered and with high patient satisfaction. In-hospital days could be reduced with 52% out of a total of 1197 treatment days. Homebased PPP has several advantages from a patient perspective and furthermore frees up in-hospital beds for patients in need of them.

Persistent Left Ventricular Diastolic Stiffening Despite Cessation of Intermittent Myocardial Stretch in Swine

ObjectiveBuilding on our observation that myocardial stretch induced by an acute elevation in left ventricular (LV) preload produces reversible systolic dysfunction and cardiomyocyte apoptosis, we recently demonstrated that swine subjected to intermittent myocardial stretch (IMS) for 2 weeks exhibit an adaptive increase in LV diastolic stiffness that protects the heart from stretch‐induced injury during subsequent periods of hemodynamic overload. The present study was designed to determine whether this pattern of myocardial remodeling and protection against stretch‐induced stunning is reversed by cessation of IMS.MethodsSwine (n=6) were instrumented with an indwelling jugular vein catheter through which phenylephrine (PE; 300 μg/min; 2 hours/day) was administered via programmable infusion pump to intermittently raise LV end‐diastolic pressure (EDP) for 2 weeks (IMS). Hemodynamic and echocardiographic responses were evaluated under propofol anesthesia at the initial study and after 2‐weeks of IMS. Daily PE infusions were subsequently stopped to provide a 2‐week period in which animals were no longer subjected to IMS. A final physiologic study was then performed (“4‐week study”) to assess the persistence of IMS‐induced alterations in LV function. At each study, serial blood sampling was performed to assess serum cTnI levels via porcine‐specific ELISA. Postmortem analysis of interstitial collagen deposition was completed on picrosirius red‐stained LV tissue sections and compared to animals subjected to 2 weeks of IMS (n=8) and age‐matched controls (n=5).ResultsAt the initial study, PE‐induced preload elevation elicited a significant increase in LV end‐diastolic volume (ΔEDV: 14±3 mL/m2, p<0.05) that caused stretch‐induced stunning and a marked elevation in serum cTnI (Figure). After 2 weeks of IMS, chamber dilatation during PE was attenuated (ΔEDV: 4±1 mL/m2, p=ns) by a significant increase in LV diastolic stiffness (ΔEDP/ΔEDV during PE from 0.8±0.2 to 2.3±0.5 mmHg/mL, p<0.05) that prevented stretch‐induced systolic dysfunction and cTnI release (Figure). Adaptive LV stiffening (ΔEDP/ΔEDV: 3.3±1.4 mmHg/mL) and protection against stretch‐induced injury (ΔEDV: 3±1 mL/m2) were still observed at the 4‐week study despite cessation of IMS during the previous 2 weeks. Persistent LV diastolic stiffening was also demonstrated by admittance catheter‐derived assessment of the EDPVR, which revealed an increase in the LV stiffness constant (β) at the 2‐week (0.055±0.013) and 4‐week (0.043±0.009) studies compared with normal controls (0.025±0.003; both p<0.05). Consistent with the notion that IMS‐induced remodeling is not reversed by cessation of episodic preload elevation, interstitial collagen deposition after the 4‐week study (16.3±1.1%) was comparable to that observed in animals subjected to 2 weeks of IMS (11.2±1.3 %) and significantly higher than normal controls (6.6±0.7 %).ConclusionThese results demonstrate that IMS‐induced LV diastolic stiffening is not reversed by simply discontinuing transient episodes of hemodynamic overload. This likely relates to an inability to replenish myocytes lost to stretch‐induced apoptosis and remove interstitial collagen without additional regenerative and/or anti‐fibrotic therapy. These findings may have implications for the treatment of patients with heart failure with preserved ejection fraction whom exhibit LV stiffening without persistent hypertension or anatomic LV hypertrophy.Support or Funding InformationSupported by the National Heart Lung and Blood Institute (HL‐055324 and HL‐061610), the American Heart Association (17SDG33660200), the National Center for Advancing Translational Sciences (UL1TR001412), the Department of Veterans Affairs (1IO1BX002659), and the Albert and Elizabeth Rekate Fund in Cardiovascular Medicine.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Abstract 5146: Establishment of an orthotopic bladder cancer model to evaluate continuous intravesical delivery of small molecule inhibitors in the nude rat

Abstract Bladder cancer is a disease with high unmet need, with no new treatments being registered in the last two decades. Intravesical delivery is an attractive option for organ-confined bladder cancer; indeed, non-muscle invasive disease is currently treated by intravesical administration of agents such as bacillus Calmette-Guerin (BCG) and mitomycin C, and neoadjuvant intravesical therapy has the potential to preserve the bladder and improve survival in M0 muscle invasive disease. Intravesical delivery has the potential to increase the therapeutic index compared with systemic dosing routes, particularly if the duration of exposure can be extended. In order to explore this concept, we have developed an orthotopic model of bladder cancer and a drug delivery method to administer gemcitabine into the nude rat bladder for one week. An orthotopic model of bladder cancer was established by serial passaging of MGH-U3 human bladder cancer cells into the muscle wall. Tumor take-rate and growth was monitored by ultrasound imaging. Serial ex vivo - in vivo passaging increased growth and take rate of the tumors in both orthotopic and subcutaneous locations. Orthotopic implantation of cells following two previous passages in vivo resulted in reproducible tumor growth and take rates of >90%. Immunohistochemistry analysis showed that the orthotopic tumors were stably epithelial in phenotype after three serial in vivo passages. Principal component analysis of gene expression (GE) data from RNA sequencing of the parental cell line, sequentially passaged cells growing ex vivo, and both subcutaneous and orthotopically implanted tumours after various numbers of passages revealed three clusters; two distinct but closely related clusters representing the orthotopic and subcutaneously growing tumors, and another distinct cluster representing the various cell lines. This analysis showed that in vitro/in vivo location of growth is a more important determinant of global GE than the process of serial passaging in vivo. We have used the iPRECIO programmable infusion pump system to continuously infuse gemcitabine into the bladders of rats with orthotopic bladder tumors. Infusion of 2.5 mg/day at a flow rate of 5 ul/h for 7 days resulted in urine concentrations in the range of 1- 10 mM (∼ 1000-fold greater than systemic plasma drug concentrations), a 4-fold increase of γH2AX and induction of both necrosis and apoptosis (10-fold induction of cleaved casapse 3) in the orthotopic tumors. This model system holds considerable potential for evaluation of intravesical small molecule therapies that are potentially translatable to patients. Citation Format: Leigh J. Williams, Stephanie K. Klein, Danielle Greenawalt, Dawn Trueman, Helen Musgrove, Helen Jones, Linette Ruston, Barry R. Davies. Establishment of an orthotopic bladder cancer model to evaluate continuous intravesical delivery of small molecule inhibitors in the nude rat. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5146. doi:10.1158/1538-7445.AM2015-5146

Assessment of telemetry and fluidic control system used in the Medstream programmable infusion system: an in vivo and in vitro study.

The MedStream Programmable Infusion Pump, an intrathecal pump indicated for the treatment of chronic intractable pain and severe spasticity (CE-mark) or severe spasticity (US), has a highly accurate medication delivery (within 10% of the programmed flow rate) and is certified for use in 3-Tesla magnetic resonance imaging systems (conditional). Performance of the telemetric link between external control-unit and implanted pump was assessed in sheep (in vivo) up to 26 weeks, resulting in 1040 communication sessions. The telemetric communication envelope (communication distance and maximum antenna tilt angles) and communication duration were characterized in an in vitro test. Capacitance measurements of the piezoelectric actuator of the valve, valve flow rates, and leak rates were measured in an in vitro cyclic accelerated aging test to assess reliability of the valve over 6,200 k cycles. The pump was well tolerated in vivo; all communication sessions between control-unit and pump were successful (P = 6.889 × 10(-14)). Mean communication distance between pump and control-unit was 3.8 cm, with the maximum antenna tilt angles being 40° (θy) and 50° (θx) for all test cases; the maximum communication duration was 5.5 s. Capacitance measurements, flow rates, and leak rates were within ±10 % range up to 6,200 k cycles corresponding to approximately 10 times the valve cycles over the specified service life of the pump (8 years), except for one flow-rate value, which can be explained by the measurement setup. These results demonstrate the reliability of the telemetry link and piezoelectric valve system of the MedStream Programmable Infusion Pump.

A novel type of implantable and programmable infusion pump for small laboratory animals

Introduction The iPRECIO™ (Primetech Corporation, Tokyo, Japan) is a new form of pump for infusing small laboratory animals. The key features of the iPRECIO™ are that it can be implanted within the animal, it is refillable, and it is programmable. The infusion start-points and end-points are adjustable, infusion rate can be altered, and the infusion solution can be changed after the pump is implanted. In order to confirm the precision of the iPRECIO™, in vivo and in vitro experiments were employed. Methods In the in vitro experiment, at the excretion rate of 1 μl/h for 336 h, 15 μl/h for 96 h, and 30 μl/h for 120 h, the decrease in each pump weight was used to estimate the actual excretion volume. In the in vivo experiments, the iPRECIO™ was chronically implanted in rats, angiotensin II was infused, and arterial pressure (AP) was monitored. Results In the in vitro experiment, the volume of solution excreted from the pump increased with time, and the volume excreted matched the programmed volume. The infusion rate also changed at the scheduled time. In the in vivo experiment, AP increased and decreased on schedule, and a dose-dependent pressor response to angiotensin II occurred. Furthermore, after exchanging saline with angiotensin II, AP increased and decreased on schedule. Discussion Present data of the in vitro and in vivo experiments indicates that the iPRECIO™ worked precisely, making it suitable for a variety of experiments involving small laboratory animals.

Programmable Infusion Pump and Catheter: Evaluation Using 3-Tesla Magnetic Resonance Imaging

Objective. This study assessed 3-Tesla magnetic resonance imaging (MRI) issues for a programmable infusion pump and associated catheters. Methods. A programmable infusion pump and associated catheters (MedStream Programmable Infusion Pump, 40mL; SureStream TI Coil-Reinforced Intraspinal Catheter; SureStream TI Connector; and SureStream Silicone Catheter; Codman and Shurtleff Inc., a Johnson & Johnson Company, Raynham, MA, USA) underwent evaluation for magnetic field interactions (deflection angle and torque), heating (transmit/receive body radiofrequency coil; whole-body averaged specific absorption rate, 3W/kg for 15min), functional changes (before and after MRI using eight different MRI conditions), and artifacts (T1-weighted spin-echo and gradient-echo pulse sequences) at 3-Tesla. Results. The programmable infusion pump and associated catheters exhibited minor magnetic field interactions. Heating was not excessive (≤1.9°), especially considering the experimental conditions used for this evaluation (ie, relatively high radiofrequency power/specific absorption rate level and use of a nonperfused phantom). The function of three out of six pumps was temporarily altered by exposures to 3-Tesla MRI conditions. Reset was achieved in each case. Artifacts were relatively large for the pump and minor for the catheter. Conclusions. The programmable infusion pump and catheters will not pose increased risk to a patient examined using 3-Tesla MRI as long as specific safety guidelines are followed, which includes interrogation of the pump post-MRI to ensure proper settings. Artifacts for the programmable infusion pump may impact the diagnostic use of MRI if the area of interest is in the same area or near the device.

Programmable Infusion Pumps in ICUs: An Analysis of Corresponding Adverse Drug Events

BackgroundPatients in intensive care units (ICUs) frequently experience adverse drug events involving intravenous medications (IV-ADEs), which are often preventable.ObjectivesTo determine how frequently preventable IV-ADEs in ICUs match the safety features of a programmable infusion pump with safety software (“smart pump”) and to suggest potential improvements in smart-pump design.DesignUsing retrospective medical-record review, we examined preventable IV-ADEs in ICUs before and after 2 hospitals replaced conventional pumps with smart pumps. The smart pumps alerted users when programmed to deliver duplicate infusions or continuous-infusion doses outside hospital-defined ranges.Participants4,604 critically ill adults at 1 academic and 1 nonacademic hospital.MeasurementsPreventable IV-ADEs matching smart-pump features and errors involved in preventable IV-ADEs.ResultsOf 100 preventable IV-ADEs identified, 4 involved errors matching smart-pump features. Two occurred before and 2 after smart-pump implementation. Overall, 29% of preventable IV-ADEs involved overdoses; 37%, failures to monitor for potential problems; and 45%, failures to intervene when problems appeared. Error descriptions suggested that expanding smart pumps’ capabilities might enable them to prevent more IV-ADEs.ConclusionThe smart pumps we evaluated are unlikely to reduce preventable IV-ADEs in ICUs because they address only 4% of them. Expanding smart-pump capabilities might prevent more IV-ADEs.

The Use of Implanted Programmable Infusion Pumps in the Management of Nonmalignant, Chronic Low-Back Pain

Objectives. To assess the mode-of-use of implanted programmable infusion pumps in patients with nonmalignant, chronic low-back pain. Materials and Methods. Charts from 101 consecutive eligible patients were analyzed retrospectively. Data were extracted relating to patient demographics, pump mode of infusion and flow rate, and medications used. Results. Morphine was the agent most frequently used and most patients received one medication at each visit. At the last visit, 94.1% of patients were receiving constant-flow treatment; 90.1% had received such treatment for≥sixmonths and 68.3% throughout the entire analysis period. For patients attaining constant-flow treatment, mean time from implantation to start of such treatment was 2.7months. Discussion. The results suggest that many patients with nonmalignant low-back pain could be implanted with a constant-flow pump when their programmable device needs replacing or, in some cases, at the start of intrathecal treatment. This would reduce costs and the requirement for surgery.

Treatment of severe spacticity in multiple sclerosis by continuous intrathecal baclofen

Successful treatment of severe spasticity represents an imperative of symptomatic therapy of multiple sclerosis (MS) due to a significant improvement of physical, psychic and social rehabilitation of MS patients, as well as a long-term cost savings for the additional treatments of conditions arising from uncontrolled severe spasticity. Continuous intrathecal administration of baclofen (ITB), using a subcutaneously implanted programmable infusion pump, is a minimally invasive, reversible method for the treatment of severe diffuse spasticity of the spinal origin. The first two cases in our country, treated by ITB due to severe spasticity caused by MS, were reported. Despite the local complications of surgical wound healing above the implanted components of the ITB-system in one patient, the optimal reduction of spasticity the with complete elimination of spastic pain was obtained in both patients. Our initial experiences confirmed ITB as a safe and effective therapeutical option for the treatment of intractable spasticity in patients with MS. Major prerequisites for this were adequate patient selection and good control of the basic disease. The use of the minimal invasive implantation technique and the experience in choosing of the adequate ITB-system components, could successfully prevent the occurrence of local complications related to the impaired healing of the ITB-system implantation site.

Patient-Controlled Analgesia

One of the most common methods for providing postoperative analgesia is via patient-controlled analgesia (PCA). Although the typical approach is to administer opioids via a programmable infusion pump, other drugs and other modes of administration are available. This article reviews the history and practice of many aspects of PCA and provides extensive guidelines for the practice of PCA-administered opioids. In addition, potential adverse effects and recommendations for their monitoring and treatment are reviewed.

Standardized Vasoactive Medications: A Unified System for Every Patient, Everywhere

Providing medications used in emergency cardiovascular care (ECC) in an efficient and consistent manner is a cornerstone for achieving excellent patient care and safety. For neonatal, pediatric, and adult patients who move through different specialty areas in a tertiary hospital, it is essential to have a standardized protocol for these medications that can be followed regardless of location or practitioner. Our institution developed a protocol for intravenous push (IVP) and continuous infusion (CI) medications based on the Neonatal Resuscitation Program (NRP), Pediatric Advanced Life Support (PALS) and Advanced Cardiovascular Life Support (ACLS) guidelines. This protocol incorporates these guidelines into a single reference sheet (Emergency Drug Sheet) based on the patient's weight using a computer software program. The program provides the option for either pediatric (weight-based) or adult (weight-based and standard dose) dosing. The CI section uses a limited number of concentrations, which meets the JCAHO mandate. Commercially available products are used, when possible, in response to USP <797>. It also serves as the standard protocol for vasoactive medications in all patient care settings in conjunction with programmable infusion pump technology. The software program is easy to use; the Emergency Drug Sheet is easy to read; and the program is available everywhere in the hospital. The standard CI protocol used with the Emergency Drug Sheet reduces unclear orders, standardizes drug preparation, and decreases the time to medication delivery. It could serve as a model for community hospitals, as well as tertiary facilities.

Manejo de la espasticidad en pacientes con lesión medular con infusión de baclofeno intratecal mediante bomba implantable

This article presents three cases of severe medullar lesion following trauma, resulting in tetraplegia and severe spasticity, and evaluates the safety and efficacy of treatment with intrathecal baclofen. In order to evaluate the patients' reaction to intrathecal baclofen, they were tested with trial doses of baclofen via a spinal tap prior to implanting the pump. This treatment brought a significant reduction of rigidity and spasticity for more than eight hours in all three cases rated according to Ashworth and Penn Spasm Frequency scales. A programmable infusion pump with an intrathecal catheter for administration of baclofen was then implanted in all three patients. The patients underwent neurological checkups every three months. They all showed satisfactory clinical improvement with progressive adjustments to the baclofen doses. No serious complications have been observed

An automated drug delivery system for focal epilepsy

Previous studies have demonstrated the ability to stop seizures in animal models with injection of antiepileptic medication directly onto the seizure focus. The present experiments describe automated detection and focal therapy for seizures in the laboratory setting. Focal seizures were created in Sprague–Dawley rats using bicuculline, a GABA antagonist. Computerized detection of seizures was linked to a programmable infusion pump to deliver either diazepam (DZP) or pH-balanced vehicle (VEH) directly onto the seizure focus. Mean numbers of seizures following initial delivery of drug were 2.9±1.45 for the VEH-treated group and 0.2±0.42 for the DZP-treated group ( P<0.0001, Student’s t-test, nonpaired, one-tailed). In another series of experiments, early injection of DZP shortened seizure duration. Three DZP-treated animals died. This model provides proof-in-principle for the development of a clinically applicable treatment for intractable partial epilepsy. Such therapy might avoid some of the problems inherent to systemic administration of antiepileptic drugs.