Regional Infusion Therapy Research Articles

The role of hyperosmolar solutions in the physician’s practice

Background. The goal of infusion therapy (IT) is to maintain central euvolemia without excess sodium and water. The term “restrictive IT”, which allows hypovolemia, should be replaced by the term “IT with a zero balance”. Individualized targeted IT involves monitoring cardiac output, optimizing stroke volume, and preventing episodes of hypovolemia. Less stringent restrictions on preoperative nutrition contribute to better control of hemodynamic parameters.
 Objective. To describe the role of hyperosmolar solutions in the physician’s practice.
 Materials and methods. Analysis of literature sources on this issue.
 Results and discussion. Support of perioperative euvolemia is the basis of the concept of enhanced recovery and improvement of the surgery outcomes. Clinical indices of tissue perfusion adequacy include mean blood pressure, central and abdominal perfusion pressure, diuresis, consciousness level, skin perfusion, lactate and blood pH, etc. Each patient with suspected hypovolemia should be physically examined with an emphasis on searching for bleeding, dehydration, and other causes of hypovolemia. Fluid deficiency should be compensated before surgery. Hyperhydration must also be detected and eliminated timely, as the diagnosis and prediction of pulmonary edema are difficult. There are 4 phases in IT of shock: rescue (achieving blood pressure and cardiac output required for survival), optimization (ensuring sufficient oxygen delivery and lactate control), stabilization (preventing organ dysfunction after achieving hemodynamic stability), and de-escalation (ensuring negative fluid balance). In resuscitation of patients with sepsis and septic shock, the use of hydroxyethyl starch (HES) is not recommended; crystalloids should be preferred over gelatin. If HES were still prescribed, their introduction should be stopped if there are signs of kidney damage or signs of coagulopathy. It is also proposed not to administer hyperoncotic solutions to critically ill patients outside of clinical trials. New colloidal solutions should be introduced into clinical practice only after the establishment of safety for the patient. Following an appeal by HES-manufacturing companies, the Pharmacovigilance and Risk Assessment Committee of the European Medicines Agency stated that HES could be used for massive bleeding at the discretion of the chief physician. Continued use of HES in the postoperative period should be further investigated, including monitoring of renal function for 90 days. In general, the use of HES in clinical practice remains relevant in conditions such as massive bleeding or penetrating trauma, as well as for preloading before regional anesthesia and IT of critical conditions without the risk of bleeding. Modern HES should be used and the dose should not exceed 30 ml/kg. The benefits of preoperative targeted preload optimization using HES are beyond doubt, while recommendations for the overall hazard of these solutions are debatable and inconclusive. The volume of injected solutions should be monitored during IT, as infusion of large volumes of crystalloids may cause pulmonary edema and large volumes of 0.9 % NaCl may lead to the development of hyperchloremic metabolic acidosis. Hypertonic solutions have been shown to be effective in reducing the number of abdominal complications of pancreatoduodenectomy, reducing the length of stay on mechanical ventilation in patients with hemorrhagic shock, and in a number of other interventions. Fluid resuscitation with a small volume of hypertonic saline after damage control operations significantly reduces the length of stay in the intensive care unit, decreases the likelihood of acute respiratory distress syndrome, sepsis and multiple organ failure, reduces 30-day mortality. In patients with brain injuries, hypertonic solutions reduce intracranial pressure and help to balance the fibrinolysis system by reducing secondary brain damage. Unfortunately, most (60 %) of the solutions on the market are unbalanced (Hohn R., 2014). The reasons for this include lower cost of the latter, the lack of understanding of the benefits of alternatives by doctors, the lack of awareness of the seriousness of these solutions’ disadvantages. Due to the risk of acidosis on the background of unbalanced solutions, chloride-restrictive IT should be followed. Hyperosmolar balanced solution Reosorbilact (“Yuria-Pharm”) helps to activate the sympathetic nervous system, which leads to increased blood pressure, decreased diuresis, adrenaline release and increase of circulating blood volume by contracting the spleen. Reosorbilact quickly normalizes hemodynamic parameters, microcirculation, laboratory and biochemical parameters, stabilizes and normalizes the function of external respiration and blood circulation. The use of osmotic drugs Reosorbilact and Xylate (“Yuria-Pharm”) is indicated for plasma volume replacement in hypovolemia of various origins.
 Conclusions. 1. Perioperative euvolemia is the main principle of perioperative IT. 2. It is not recommended to use HES in intensive care. 3. HES remain relevant in acute hypovolemia and blood loss. 4. Balanced hyperosmolar solutions (Reosorbilact) are an alternative to HES in the treatment of patients with multiple organ failure in intensive care units.

Temozolomide is a novel regional infusion agent for the treatment of advanced extremity melanoma

Background Regional infusion therapy with melphalan (LPAM) is an accepted treatment for advanced extremity melanoma. However, much room exists for improving the therapeutic index of this type of therapy. Methods Isolated limb infusion (ILI) with temozolomide (TMZ), a novel methylating agent, was performed using a nude rat bearing human melanoma xenograft. Additional rats were treated systemically with TMZ, or regionally with LPAM or 10% dimethyl sulfoxide (DMSO; control) using ILI. Results Rats that received systemic TMZ showed a poor tumor response and no tumor regression. In contrast, intra-arterial TMZ demonstrated a prolongation of tumor growth delay in a dose-responsive manner. In comparison with LPAM of equitoxic dose, TMZ provided both longer tumor growth delay and a greater number of tumor regressions. Conclusions These data suggest that ILI with TMZ is an effective treatment for advanced extremity melanoma and may be better than LPAM in this setting.

Combination therapy in oncology (multimodal treatment) in pancreatic tumors

The majority of patients with pancreatic cancer have systemic disease already at diagnosis, and nearly all patients will develop recurrence following radical resection. Thus, surgical treatment alone is insufficient. The paper focuses on adjuvant multimodal treatment and reviews the current status of pre- and postoperative chemoradiation, intraoperative radiotherapy (IORT), adjuvant chemotherapy, and regional infusion therapy. Studies in this area are hampered by often being non-randomized and with too few patients included. Overall there presently is no adjuvant multimodal treatment which can be suggested for routine use. However, two ongoing prospective randomized studies (ESPAC-1 and an EORTC study) will have enough statistical power to give reliable information on the topic. It is hoped that these and other studies will form the basis for further proper clinical trials on multimodal treatment in pancreatic cancer with the aim at long last to improve the extremely poor survival in these patients.

Transcatheter treatment of hepatic metastases.

After successful removal of a primary tumor, the exclusive or dominant site of metastatic spread is often the liver. Existing palliative treatments, particularly chemotherapy, have low success rates. Fortuitous physiologic circumstances allow the use of regional treatments, such as hepatic artery infusion therapy, for both primary and secondary malignant tumors in the liver. Despite encouraging results in early uncontrolled trials, subsequent randomized studies have failed to show survival benefit with regional infusion therapy via surgically implanted pumps in patients who have colorectal metastases, the most common tumor studied. Dissatisfaction with current treatments has led to a host of novel therapies, including embolization of liver tumors and the combined infusion of embolic particles and chemotherapeutic agents (i.e., chemoembolization).

Regional infusion chemotherapy for colorectal hepatic metastases—where is it going?

Colorectal cancer is the second most frequent cause of cancer death in the U.K. responsible for 22,000 deaths per annum. The incidence of hepatic metastases in those relapsing after 'curative ' surgery is at least 50°,~, and there is clearly a need tbr more effective treatment. Interest in regional inliasion chemotherapy arose because of the failure of systemic therapy to influence the course of the disease. Regional infusion chemotherapy to the liver was first at tempted over 30 years ago. Initially, t reatment was carried out using percutaneously placed angiographic catheters. However, this was associated with cracked and blocked catheters as well as gastroduodenal and hepatic toxicity. However, since 1980, interest has been rekindled due to the development of the implantable pump. The accuracy and reliability of these pumps means that patients can now receive continuous treatment as an outpatient without interfering with daily activities. The main limitations of the system are the requirement for low volume chemotherapy in a stable solution, the cost of the pump and its implantation. The requirements for regional infusion therapy for liver metastases are:

Gastroduodenal artery‐duodenal fistula: A complication of continuous floxuridine (FUDR) infusion into the gastroduodenal artery

This case report describes a patient who for 31 months has received regional intrahepatic chemotherapy from a continuous infusion pump and who developed a gastroduodenal artery-duodenal fistula, a previously unreported complication of regional infusion therapy. The patient presented with signs and symptoms of upper gastrointestinal bleeding. The clinical evaluation and management are described. An angiogram was performed through the auxillary septum to identify the source of bleeding. The possible etiologic factors in this case are discussed. We believe that this complication will continue to be rare, but health care providers should be aware of its presentation and its preferred method of evaluation and management.

Isolated liver perfusion in dogs.

The surgical treatment of liver tumors has been complemented by regional infusion therapy with cytostatics in many centres over the past few years (Ansfield et al. 1971; Misra et al. 1977; Ramming et al. 1976; Taylor 1978). The liver is thus supplied with high doses of cytostatics via the arterial or portal system. However, after passing through the liver these drugs enter the systemic circulation and cause the familiar side effects. Moreover, the results of controlled studies which have become available show that survival times could not be substantially prolonged.