Implanted Pumps Research Articles

Intravenous treprostinil via an implantable pump in pediatric pulmonary arterial hypertension

Intravenous prostacyclin-based therapy improves survival in children with pulmonary arterial hypertension (PAH), but is typically administered via an external infusion pump, which places a considerable burden on the patient. Implanted pumps may overcome some of the limitations of external pumps. We describe the first long-term use of an implanted pump for intravenous treprostinil delivery in a pediatric patient with PAH. Our patient was experiencing marked dyspnea on exertion despite triple combination therapy with bosentan, sildenafil, and inhaled iloprost. Parenteral prostacyclin-based therapy was discussed and the patient rejected options involving external pumps; she finally chose intravenous treprostinil delivery via an implanted pump (LENUS Pro®; fixed flow rate; 20 ml reservoir). The patient underwent pump implantation in July 2012 (aged 14 years) under general anesthesia with no peri- or postoperative complications. She showed marked improvements in fatigue and dyspnea over the subsequent weeks, and her inhaled iloprost regimen was slowly decreased and stopped after six months. During follow-up, the pump showed an unexpected, progressive increase in flow rate that allowed a treprostinil dose of 170 ng/kg/min to be achieved, but at the cost of shortened intervals between refills. The pump was therefore replaced in August 2017 with a newer model with an adjustable flow rate (Siromedes®). A catheter dislocation was corrected under local anesthesia one week after the replacement surgery. The patient is currently receiving treprostinil 170 ng/kg/min with percutaneous refills every 12–13 days. Thus, implantable pumps might be a valuable alternative to external pumps for treprostinil infusion in pediatric PAH.

Implantable Pump For Long-Term Chemotherapy Administration Via the Hepatic Artery: Has It Fulfilled Its Promise?

The 1983 editorial was written to highlight an article from Weiss et al utilizing an implantable pump, a technical advance that allowed long-term, relatively safe, hepatic artery infusions (HAI) of chemotherapy for patients with primary or metastatic lesions in the liver. Metastatic spread to the liver occurs in 50% to 60% of patients with colorectal cancer, and eventually leads to death in those individuals not cured by surgery, because of tumor size, involvement of both lobes,orinsufficientliverreserve.Long-termintra-arterialchemotherapy has the potential to deliver higher doses of drug to the tumors compared with systemic treatment and with less systemic toxicity. The ideal drug in this regard is florodeoxyuridine (FUDR), as it is metabolized rapidly by the liver (first pass); thus, only small amounts escape into the circulation. What has happened during the past 25 years? As predicted in the editorial, the implantable pump has allowed “the exploration of other drugs and dosage schedules, as well as innovative techniques to deliver drugs at the tumor site.” Various drugs have been delivered via HAI to treat colorectal cancer; however, no single agent has been proven to be better than FUDR. The addition of LV has increased the response rate, and dexamethasone (Dex) has decreased the incidence of biliary toxicity, the major toxicity of HAI. Drawbacks to the use of implanted pumps for HAI have been the cost, and the need for an experienced team of surgeons and medical oncologists. The effort required and the lack of clear benefit, together with advances in the systemic treatment of liver metastases from colorectal cancer have relegated this approach to a few centers with expertise and with innovative ideas that attempt to utilize HAI to deliver novel therapies, such as replicating viruses to the tumor, or to use intra-arterial FUDR in combination with systemic therapy to deal with systemic spread of tumor despite control of liver metastases. Two recent studies deserve mention. The first is a Cancer and Leukemia Group B study that illustrates the difficulty of doing a randomized trial of HAI versus systemic drug delivery. In this multi-institutional 24-month trial that took 4 years to accumulate 135 patients, the overall survival was significantly longer for patients receiving FUDR/LV/Dex via HAI (24 months) as compared with patients treated with systemic fluorouracil/LV using the 5-day schedule (20 months). Previous studies demonstrated a doubling of the response rate with HAI, but not an increase in survival. The second recent study of note added either systemic oxaliplatin plus irinotecan to intra-arterial FUDR/Dex or systemic oxaliplatin, FU/LV to intra-arterial FUDR. Although a small study, the responses of patients were 90% for the first regimen and 87% for the second regimen. Remarkably, seven of 18 patients treated with the oxalopitecan plus irinotecan plus FUDR/Dex regimen became operable and had residual tumor resected. Where do we go from here? Clearly, as systemic therapy of colorectal cancer improves, we may eventually forgo the use of HAI and the need for the implantable pump. However, given that the best way to deliver a fluoropyrimidine to patients with hepatic metastases from colorectal cancer is via HAI, the combination of systemic chemotherapy and intra-arterial chemotherapy with FUDR, in patients with isolated liver metastases that are not candidates for resection makes sense. This option seems also to more effective in patients with liver metastases in first relapse after initial therapy as compared with systemic therapy. The implantable pump has fulfilled its promise, and we look forward to additional innovative use of this method to deliver antitumor agents to the liver to improve the outcome of patients with liver metastases from colorectal cancer.

Implantable insulin pumps: the Veterans Administration Study, a decade later

The Veterans Administration Cooperative Study (VACS) on implanted pumps was a pioneering experience which produced relevant information worthy of reconsideration even 10 years later. It was the first, and still the only, multicenter, randomized clinical trial of implantable insulin pump (IIP) therapy accomplished independent of industry. In a cohort of 121 type 2 diabetics already treated with insulin the study demonstrated a significant benefit of IIP in terms of stability of glycaemic control, reduction of hypoglycaemic events, reduced weight increase and improved quality of life. Furthermore the study was important in introducing a group of important academic centres to the use of IIP therapy. A series of sub-studies contributed productively. Altered production of pump insulin during the study, the short period of observation (one year), unavoidable biases introduced by the unblinded and unprotocolized insulin adjustments were limitations. Neverthless, the VACS, as an independent, rigorous multicenter trial, was successful in demonstrating certain benefits of IIP therapy and raising its profile in the U.S.A.

The EVADIAC experience

The EVADIAC association (EVAluation dans le Diabète des Implants ACtifs) was created in 1990 in Cassis, France, at the beginning of implanted insulin pump treatment in France. In fact the first four centers (Strasbourg, Marseille, Montpellier, Toulouse) experiencing the treatment by continous intraperitoneal insulin infusion with implantable pumps (CIPII) derided to join in a group with the primary objective to monitor the safety of the technique. The founding members built the statutes of EVADIAC and the goals were defined as: • Collecting and spreading all the required elements in order to assess the quality of the diabetes treatment by active implants. • Evaluating the benefits of such a treatment in patients with diabetes in order to improve its use. • Promoting every study and research about this kind of treatment. • Communicating with all the related national and international organizations. Due to the impulse of the first president, Ph. Vague, and his successors (M. Pinget, J.P. Tauber, J.L. Selam, V. Lassmann-Vague, E. Renard, H. Hanaire-Broutin), the group enlarged and gathers now 14 centers: Bordeaux, Corbeil, Dijon, Le Mans, Lille, Lyon, Marseille, Montpellier, Paris, Reims, Rennes. St Etienne, Strasbourg, Toulouse. The energy and enthusiasm of all EVADSAC members have allowed a large development and a broad experience of insulin implanted pumps treatment in France.

A Clinical Study of Intrathecal Baclofen Using a Programmable Pump for Intractable Spasticity

Guillaume D, Van Havenbergh A, Vloeberghs M, Vidal J, Roeste G. A clinical study of intrathecal baclofen using a programmable pump for intractable spasticity. Objective To determine the impact of intrathecal baclofen (ITB) therapy on outcomes of functional independence, pain, subjective improvement, performance, and standard measures of spasticity. Design A noncomparative, multicenter, prospective cohort trial of patients with implanted pumps followed up over a 12-month period for the assessment of spasticity, pain, and function. Setting Twenty-four European centers of neurology or rehabilitation familiar with implantable pump technique participated. Participants Patients with intractable spasticity (N=138) who responded positively to a trial dose of baclofen (n=133) and who began ITB therapy (n=129) were enrolled. Intervention Implantation of a Medtronic SynchroMed Infusion System with the administration of ITB therapy. Main Outcome Measures Ashworth Scale assessment, Penn Spasm Frequency Scale scores, pain assessment, FIM instrument scores or WeeFIM scores for children, Canadian Occupational Performance Measure (COPM), and subjective ratings of overall relief were the tools administered. Results Muscle tone, spasm scores, and pain intensity reductions were observed. Overall FIM scores increased significantly in cognitive and motor function. COPM scores for both performance and satisfaction also improved significantly. Patients reported increased relief from pain and spasticity, supported by physician reports. Forty-three percent of patients reported adverse events, mostly related to patients’ underlying conditions (20%), the device implant surgery (10%), or complications with the catheter (9%). Conclusions ITB therapy using a programmable pump is clinically effective and well tolerated, despite a seemingly high level of adverse events, in patients with intractable spasticity of spinal or cerebral origin and may offer improvements in pain relief and function.

Intrathecal drug therapy using the Codman Model 3000 Constant Flow Implantable Infusion Pumps: experience with 17 cases

The objective of this study was to evaluate the accuracy, reliability, safety, and efficacy of the Codman Model 3000 Constant Flow Implantable Infusion Pump for intrathecal baclofen delivery as a therapeutic option for the treatment of severe spasticity. The distinctive features of this pump include a raised, easily palpable septum, a safety valve protecting the bolus pathway, no programmer needed, and no battery to fail. A total of 17 patients with spinal cord injury, multiple sclerosis, or cerebral palsy were implanted with this pump. The accuracy of the pump and drug treatment efficacy was determined at each visit and adjustments to the dosages were made as required. All the intrathecal drug delivery system complications were reviewed. The expected efficacy was achieved. The accuracy of the implanted pumps ranged from 90-97% (average 94%). There were no complications due to primary pump problems. The complications reported are similar to other implantable infusion devices and include dehiscence of the suture line, pressure ulcer development, formation of seroma, inversion of the pump, baclofen overdose, and catheter failures. The Codman Model 3000 Constant Flow Implantable Infusion Pump is an accurate, reliable, and convenient option for patients needing intrathecal baclofen therapy, with complications similar to other available pumps.

Immunogenicity of long-term intraperitoneal insulin administration with implantable programmable pumps. Metabolic consequences.

To assess immunogenicity of intraperitoneal insulin infusion via implanted pumps by two methods and to evaluate the possible influence of an increased antibody level on metabolic and clinical parameters. We studied insulin antibody levels in 17 type I diabetic patients before and until 24 months after implantation of a programmable pump delivering insulin intraperitoneally. Antibody levels were determined by radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA). They were correlated with HbA1c, insulin requirements, free insulin, and the incidence of hypoglycemia. Insulin antibodies increased as soon as the 3rd month after implantation. This increase was sustained throughout the study period (month 0, 25.4 +/- 16.2%; month 3, 41.2 +/- 23.5%; month 12, 45.9 +/- 26%; month 24, 48.7 +/- 25%). The data was correlated with the two assay methods (RIA and ELISA). Postimplantation level was correlated with preimplantation level, which could indicate a predictive value of the latter . No correlation was observed with any metabolic parameters, particularly the number of hypoglycemic episodes. Our results indicate that intraperitoneal insulin administration by implantable programmable pumps leads to an increase of insulin antibodies, which are probably high-affinity antibodies (recognized by both RIA and ELISA). This increase in insulin immunogenicity did not induce significant metabolic consequences, which is reassuring for the future of programmable insulin pumps.

NURSING CARE OF PATIENTS WITH IMPLANTED PUMPS

The implantable pump systems are totally implantable drug delivery systems designed for long-term infusion therapy. These systems have made it possible to maintain the regional delivery of cytotoxic agents and analgesics in a relatively safe and convenient manner for the patient. Regular maintenance is required. The nurse plays a key role in maintaining implantable pump systems, and he or she must have a thorough understanding of the systems and their various applications. Although these systems are complex, the discomfort and restrictions imposed on the patient by their use are minimal. The required maintenance is infrequent and simple enough to allow for greater mobility and freedom from hospitalization for the patient.

Intraarterial infusion chemotherapy for hepatic carcinoma using a totally implantable infusion pump.

Intraarterial infusion chemotherapy has several theoretical advantage over conventional therapy for the treatment of unresectable malignancies. However, the catheter problems and patient restriction to the hospital associated with its use have resulted in infrequent application and a notable lack of progress in this field of oncology. This paper describes the use of a totally implantable, percutaneously refillable infusion pump in 5 patients with primary or metastatic carcinoma of the liver. The infusion cannulae were placed into the hepatic arteries under direct vision at laparotomy, and the pumps were placed in subcutaneous pockets. Four patients received infusions of 5-fluorodeoxyuridine at rates of 0.2-0.5 mg/kg/day for periods of three to 29 weeks; the pump in the fifth patient was defective and was removed. The implanted pumps were well tolerated in these subjects, who received chemotherapy as outpatients; the only adverse effects noted were related to FUDR toxicity. This implantable infusion pump appears to be a practical means of delivering long-term intraarterial infusion chemotherapy to outpatients.

The effect of continuous heparin infusion for one year on serum cholesterol and triglyceride concentrations in the dog

Fourteen normal dogs received continuous infusions of intravenous heparin for one year by means of an implantable infusion pump. Heparin was admistered at an overall mean rate of 666 units/kg/day, a dose sufficient to prolong the Lee-White clotting time to greater than twice normal. Eight control, animals, under the same dietary and activity regimen, received continuous infusions of bacteriostatic water for one year by means of implanted pumps. Serum cholesterol concentrations rose to 50% above control values after one month of heparin infusion, and remained significantly ( P < 0.05) elevated at this level for the remaining 11 months. Serum triglyceride levels were unchanged. A possible mechanism for this elevation resides in the known effect of heparin to increase plasma free fatty acid concentrations by its activation of lipoprotein lipase. These results may have implications for the long-term use of heparin anticoagulation in the treatment of atherosclerotic states in man.