Implantable pumps

The driving force for drag release from a pump is a pressure difference that causes the bulk flow of a drag, or drug solution, from the device at a controlled rate. This is in contrast to the polymeric controlled release systems described above, where the driving force is due to the concentration difference of the drag between the formulation and the surrounding environment. Pressure differences in an implantable pump can be created by osmotic or mechanical action, as described below. 

Osmosis is defined as the movement of water through a semi-permeable membrane into a solution. The semipermeable membrane is such that only water molecules can move through it the movement of solutes, including drags, is restricted (although the extent of this restriction depends on the characteristics of the 

The volume flow rate arising from the influx of water into the solution is determined by a number of factors  

These parameters affecting the volume influx of water can be expressed by dV ALp(trAiT-AF) dt h 

Common semipermeable membranes and osmotic agents used in osmotic pumps are summarized in Table 4.6. 

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The ventricular assist device (VAD) is a surgically implanted pump that reduces or replaces the work of the right, left, or both ventricles. Ventricular assist devices are currently indicated for short-term support in patients refractory to pharmacologic therapies, as long-term bridge therapy (a temporary transition treatment) in patients awaiting cardiac transplant, or in some instances, as the destination therapy (treatment for patients in lieu of cardiac transplant for those who are not appropriate candidates for transplantation).1 The most common complications are infection and thromboembolism. Other... 

Fig. 24 (A) top view and (B) a cross-sectional illustration of the INFUSAID Model 400 implantable pump. (Courtesy of Infusaid Inc., Norwood, MA.)...

P. J. Blackshear, Implantable pumps for insulin delivery Current clinical status, in Drug Delivery Systems, Fundamentals and Techniques (P. Johnson and J. G. Lloyd-Jones, eds.), Ellis Horwood, Chichester, 1987, p. 139. 

A new trend in the delivery of medicines is to employ a device component. This may be an implantable pump for insulin, a metallic stent coated with a drug, or unit capable of rapidly vaporizing a discrete dose for inhalation. Such products are regulated by the FDA as "combination" products and may be reviewed by multiple Centers within the Agency, which may require additional levels of documentation to support the product design. 

Intrathecal Management of severe spasticity of spinal cord origin in patients who are unresponsive to oral baclofen therapy or experience intolerable CNS side effects at effective doses. Intended for use by the intrathecal route in single bolus test doses (via spinal catheter or lumbar puncture) and, for chronic use, only in implantable pumps approved by the FDA specifically for the administration of baclofen into the intrathecal space. 

The currently available percutaneously implanted pumps offer short term ventricular support only. They have been mostly used in acute cardiogenic shock to provide acute hemodynamic stability before another definitive therapy like revascularization, surgical LVAD, or transplantation. Following is a description of the currently available percuatneous LVADs. 

Repeated episodes of catheter obstruction by fibrin clots or omental encapsulation can be a problem during continuous peritoneal insulin infusion from implanted pumps (SEDA 20, 397). In the encapsulated tissue, collagen fibrosis, inflammatory reactions with lymphocytes, and amyloid-like deposits reacting to anti-insulin antibodies can occur higher macrophage chemotaxis may also promote these processes. 

Diabetes mellitus in a 36-year-old man with acute pancreatitis could not be controlled with continuous subcutaneous insulin infusion, even with doses up to 1800 U/ day, because of insulin resistance (168). Intravenous insulin by pump had to be stopped because of a catheter infection. The continuous subcutaneous infusion of freeze-dried insulin and the addition of aprotinin, a protease inhibitor, soluble dexamethasone or prednisolone, and intravenous immunoglobulin was ineffective. An implantable pump for intraperitoneal delivery established good regulation at a dosage of 30 U/day. 

Continuous intraperitoneal insulin infusion with implantable pumps has been assessed in 34 patients with poorly controlled diabetes (231). In two patients, the pump was explanted in one patient with Werner s syndrome (no subcutaneous fat) the pump was explanted because of infection in the pocket, and one pump was explanted because the patient had local complaints and psychological problems. One patient refused to be included. Patients were followed for 58 months. HbAic fell from 10.0 to 9.0% in the first year and remained there. Median days in hospital fell from 45 to 13 after 1 year. The quality of life was relatively low and many had psychiatric problems. Although long-term glycemic control improved and lengths of hospital stay were reduced, normal glucose control and normal quality of life could not be achieved. 

There was no macrophage activation in 10 patients with obstructed (n = 3) or non-obstructed (n = 7) catheters in implantable pumps (239). 

Problems with insulin delivery in implanted pumps are difficult to correct. A change in Hoechst 21 pH-neutral semisynthetic insulin 400 U/ml in accordance with regulations of the European Pharmacopoeia (SEDA-20, 397) resulted in more frequent clogging when this insulin was used in the Minimed 2001 implantable pump (MIP 2001). From October 1995 to October 1996, 17 pumps were implanted (241). The refilling period was reduced from 90 to 30-45 days and the reservoirs were washed with insulin-free buffer before each refill. Backflow was seen in 13 pumps after a mean period of 7.2 months. Modification of the manufacturing process produced 21PH ETP insulin (human semisynthetic insulin, Genapol-stabilized) 400 U/ml, Hoechst, with improved stability since July 1997. All pumps were specifically cleaned before the new insulin was used for refill. The refill period was increased from 38 to 78 days. In 16 pumps, only one backflow was seen after 14 months. 

The incidence of catheter blockage did not change. The better stability of this insulin for implantable pumps has been confirmed in a study in which 88 pumps were refilled every 45 days and 108 pumps every 90 days (242). 

Riveline JP, Capeau J, Robert JJ, Varroud-Vial M, Cerf-Baron I, Deburge A, Charpentier G. Extreme subcutaneous insulin resistance successfully treated by an implantable pump. Diabetes Care 2001 24(12) 2155-6. 

Pinget M, Jeandidier N. Long term safety and efficacy of intraperitoneal insulin infusion by means of implantable pumps. Horm Metab Res 1998 30(8) 475-86. 

Kessler L, Tritschler S, Bohbot A, Sigrist S, Karsten V, Boivin S, Dufour P, Belcourt A, Pinget M. Macrophage activation in type 1 diabetic patients with catheter obstruction during peritoneal insulin delivery with an implantable pump. Diabetes Care 2001 24(2) 302-7. 

Renard E, Souche C, Jacques-Apostol D, Lauton D, Gibert-Boulet F, Costalat G, Bringer J, Jaffiol C. Improved stability of insulin delivery from implanted pumps using a new preparation process for infused insulin. Diabetes Care 1999 22(8) 1371-2. 

Rosenthal K. Implantable pumps deliver innovative pain management. Nurs Manage. 2003 34 46-49. 

In parenteral therapy, the subcutaneously implantable, osmotic mini-pumps developed by the Alza Corp. are used widely in experimental animal studies. The DUROS implant pump is a modified version of the Alzet pumps and was developed specifically for the controlled delivery of peptides and proteins (see Section 4.6.1.2). Osmotic mini-pumps, such as the Oros osmotic pump, are also available for controlled... 

Table 4.6 Semipermeable membranes and osmotic agents commonly used in osmotic pressure-activated implantable pumps...

The Duros implant pump is a modified version of the Alzet miniosmotic pump which additionally contains a piston to control drug flow, between the osmotic engine and the drag resorvoir (Figure 4.18). 

The advance in microelectronics in the 1970s provided the momentum to develop externally programmable implantable pump systems. Such pumps were finally developed in the early 1980s and they allow physicians and patients to precisely control the infusion rate of a drag. Thus externally programmable pumps can facilitate ... 

The SynchroMed implantable pump was the first externally programmable implant pump to be introduced in the United States (in 1988). The major components are a miniature peristaltic pump, a drag reservoir (18 ml), a battery, an antenna, a microprocessor and a catheter through which infusate is delivered to a specific site. 

In the MiniMed implantable pump, a piston pump drives insulin through the delivery catheter. A patented solenoid motor controls the piston movement, to aspirate insulin from the reservoir chamber into the piston chamber and then push it through the insulin delivery catheter. 

The Arrow implantable pump is non-programmable and delivers infusate (2-deoxy-5-fluorouridine, morphine sulfate, baclofen, or heparinized saline) at 3 pre-set flow rates. The pump is divided into two chambers by accordion-like movable bellows. Infusate is placed in the inner dmg reservoir chamber and Freon propellant in the outer chamber (Figure 4.19). 

Figure 4.19 The cross-sectional view of the Arrow model 3000 implantable pump, showing the pumping mechanism...

The Infusaid pump is another fixed-rate implantable pump that shares many similar features, including the Freon pumping principle, with the Arrow pump. 

What is the principle that has been utilized in the development of the Alzet and the Duros implant pumps in which a dmg solution or suspension is confined in a semi-permeable membrane that allows only water molecules to move through it ... 

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