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Intermittent subcutaneous injections for symptom control in hospice care: a retrospective investigation.

An alternative route to oral medications used by some hospice programs is intermittent injections of medications using an indwelling subcutaneous butterfly needle. The nurse places the infusion sets and instructs caregivers on medication administration. Although this method has become more common in hospice care, it has not received much attention in part because of a lack of data to support its efficacy. This study describes the use of intermittent subcutaneous medications for symptom relief in a home hospice program. A chart review was conducted of the 191 patients who received medications by this route during three calendar years; 77% had cancer. The average duration of hospice care was 25 days; on average, intermittent subcutaneous medications were instituted 4 days prior to the patient's death. The main indications for this route were inability to swallow/somnolence (65%), and pain unresponsive to oral medication (19%). Symptoms to be controlled by this method were pain (88%), anxiety (72%), and dyspnea (4%). Morphine was used most frequently for pain, and Ativan was used most frequently for anxiety. Side effects from the medications and problems with this route of administration were rarely reported, thereby supporting the practicality of this method in hospice care. These results form the foundation for a prospective study that is documenting staff, patient, and caregiver variables that impact on the effectiveness and manageability of this method of symptom management in hospice care.

Adult↗

Pharmacokinetic model to describe the lymphatic absorption of r-metHu-leptin after subcutaneous injection to sheep.

PURPOSE: The purpose of this work was to develop a pharmacokinetic model to describe the contribution of the lymphatics to the absorption and bioavailability of r-metHu-Leptin administered by subcutaneous (SC) injection to sheep. METHODS: r-metHu-Leptin was administered either by bolus intravenous injection (0.1 mg/kg) into the jugular vein or by SC injection (0.15 mg/kg) into the interdigital space of the hind leg. The SC groups included a non-cannulated control group and a lymph-cannulated group, in which peripheral lymph was continuously collected from a cannula in the efferent popliteal lymph duct. Serum and lymph concentrations were determined by enzyme-linked immunosorbent assay and profiles were modeled using compartmental pharmacokinetic methods. The fraction of the dose reaching the systemic circulation (Fsys) and the proportions of the absorbed dose taken up via the blood (Fblood) and lymph (Flymph) were determined. RESULTS: Serum and lymph concentration vs. time profiles were well described by a two compartment model with parallel first order absorption into blood and lymph. Fsys for the SC control group was 60.4 +/- 8.4%. In the lymph-cannulated group, 21.7 +/- 6.4% of the dose was recovered in serum and 34.4 +/- 9.7% was recovered in peripheral lymph giving a total fraction absorbed (Fabs) of 56.0 +/- 10.3%. Fsys for the SC control group was not significantly different to Fabs in the lymph-cannulated group. CONCLUSION: This study has shown that the lymph represents the predominant pathway for absorption of r-metHu-Leptin after SC administration.

Animals↗

Serum complement activity and serum enzymes in rats after a subcutaneous injection of toxin prepared from Pasteurella multocida type D.

Toxin produced by Pasteurella multocida type D was investigated for its effect on serum complement and serum biochemistry in rats. Rats were given a sublethal single subcutaneous injection of D toxin equivalent to 0.2 microgram/kg of body weight. Serum obtained 1, 3, 5 and 7 days post-treatment was tested for complement activity, total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP). Serum complement titers were significantly elevated (P less than 0.05) at all times after injection of toxin compared to rats injected with diluent and tested at the same intervals. Bilirubin was decreased but both control and D toxin-treated rats had low concentrations of bilirubin in their sera. The other biochemical constituents measured had no consistent pattern that would indicate liver damage in the rats.

Alanine Transaminase↗

Efficacy of the fluorescent dyes Fast Blue, Fluoro-Gold, and Diamidino Yellow for retrograde tracing to dorsal root ganglia after subcutaneous injection.

The present study was designed to investigate the efficacy of the fluorescent dyes Fast Blue (FB), Fluoro-Gold (FG), and Diamidino Yellow (DY) for retrograde tracing of lumbar dorsal root ganglia after their subcutaneous injection into different hindlimb digits. Injections of equal volumes (0.5 microl) of 51% FB or 2% FG resulted in similar mean numbers of sensory neurones labelled by each tracer. Injection of equal volumes (0.5 microl) of FB or FG in a single digit followed 10 days later by a second injection of the same volume of 5% DY into the same digit resulted in similar mean numbers of labelled sensory neurones for each of the three tracers. Furthermore, on average, 75% of all the FB-labelled cells and 74% of all FG-labelled cells also contained DY. Repeating the same experiment with an increased volume of DY (1.5 microl) resulted in an increase in the mean number of double-labelled profiles to 82 and 84% for FB and FG, respectively. The results show that FB, FG and DY label similar numbers of cutaneous afferents and that a high level of double labelling may be obtained after sequential injections in digits. These properties make them suitable candidates in investigations where a combination of tracers with similar labelling efficacies is needed.

Animals↗

The role of lymph node cells in the inhibition of metastasis by subcutaneous injection of Lactobacillus casei in mice.

The role of lymph node cells in the inhibition of metastasis of B16-BL6, a highly metastatic variant of B16 melanoma, by Lactobacillus casei YIT9018 (LC 9018) in C57BL/6 mice was determined. Subcutaneous (s.c.) injection of LC 9018 into the left inguinal or the left axillary region inhibited both axillary lymph node and lung metastasis of B16-BL6 after surgical excision of the tumors resulting from inoculation into the left front footpad of the mice. There was, however, little inhibition of the metastasis when LC 9018 was given in the inguinal or axillary region opposite the tumor inoculation. The s.c. injection of LC 9018 into the left inguinal region also augmented not only the cytolytic activity of the left inguinal lymph node cells but also the left axillary lymph node cells against B16-BL6 in vitro. However, the antimetastatic effect of LC 9018 was decreased when LC 9018 was injected s.c. into mice in which the left inguinal lymph nodes had been resected. Furthermore, natural killer cell activity of the left inguinal lymph node cells from mice injected s.c. with LC 9018 was augmented. These results suggest that the lymph node cells activated by the s.c. injection of LC 9018 played an important role in the inhibition of the metastasis and that the treatment with LC 9018 augmented the host immune response.

Adjuvants, Immunologic↗

Influence of subcutaneous injection site on the steady-state pharmacokinetics of enfuvirtide (T-20) in HIV-1-infected patients.

BACKGROUND: Enfuvirtide is the first in a new class of antiretrovirals (ARVs), the fusion inhibitors, and the first ARV to be administered by subcutaneous (s.c.) injection. OBJECTIVES: The primary objective of this study was to determine the steady-state pharmacokinetics and relative bioavailability of enfuvirtide following sc injection at three separate anatomical sites: abdomen (A), thigh (B) and arm (C). STUDY DESIGN: A single-center, open-label, multiple-dose, three-way randomized, crossover study. Twelve HIV-1-infected adults were recruited from three ongoing Phase II enfuvirtide clinical trials and randomized into three groups. Each group continued to receive s.c. injection of enfuvirtide, at a dose of 90 mg twice daily (bid), according to one of three treatment sequences: ABC, BCA or CAB; over three consecutive periods of approximately 7 days each. Plasma concentrations of enfuvirtide and its metabolite (Ro 50-6343) were measured using a validated liquid chromatography-tandem mass spectrometry method. RESULTS: The relative bioavailability of enfuvirtide, based on AUC12h and abdomen as a reference site, was 101% for thigh and 117% for arm. The AUC12h of Ro 50-6343 ranged from 14 to 16% of that for enfuvirtide. Although injection site reactions (ISRs) were common, the overall grading (based on pain or discomfort) of all reported ISRs was Grade 1 (mild). The incidence of ISRs varied according to the site of injection, as did the signs and symptoms associated with them. No patient required treatment for an ISR. CONCLUSIONS: Comparability among the three injection sites, in terms of both absorption and the ISR profile, allows HIV-1-infected patients the freedom to choose and to rotate, if necessary, the site of enfuvirtide injection among the three anatomical sites.

Dose-Response Relationship, Drug↗

[Low-dose oral etoposide and subcutaneous injection of low-dose cytosine arabinoside (Et-A non i.v.) with or without minimum anthracycline for refractory acute non-lymphoblastic leukemia].

Low-dose oral etoposide (50 mg for 10 to 14 days) and low-dose subcutaneous injection of cytosine arabinoside (15-20 mg/12 hours for 14 to 17 days) (Et-A non i.v.) were given to refractory acute non-lymphoblastic leukemia patients. Case 1 was a 47-year-old woman who had a relapsed M0. B-DOMP therapy failed but she recovered from severe infection. She had to go home to take care of her children. Et-A non i.v. was given for 14 days and 11 mg of mitoxantrone was added on the 3rd day. She achieved a complete remission (CR). Case 2 was a 72-year-old woman classified M4. Low-dose cytosine arabinoside (Ara-C) with additional daunorubicin (DNR) therapy failed. She became weaker due to the gastrointestinal toxicity of DNR. Et-A non i.v. was tried. Oral etoposide (Et) for 10 days and Ara-C for 14 days proved effective, and she achieved CR. Case 3 was a 59-year-old man with M4 developed from myelodysplastic syndrome, complicated with infection. Ara-C low-dose therapy was begun, but it was not effective. It was switched to Et-A non i.v., 40 mg of DNR was added, with 12 mg of mitoxantrone and double administration of 3 mg of vindesine. He also achieved CR. Et-A non i.v. therapy is effective and available for induction therapy with low toxicity and convenient to daily life.

Aged↗

Thermoregulatory responses of the rabbit to subcutaneous injection of sulfolane.

Earlier studies have shown that intraperitoneal injection of the industrial solvent sulfolane (tetrahydrothiophene-1,1-dioxide) caused a decrease in metabolic rate and a rapid, regulated hypothermia in mice and rats. In the present study, subcutaneous injections of 0, 100, 200, 400, 600, and 750 mg/kg sulfolane at an ambient temperature (Ta) of 10 degrees C caused a dose-dependent decrease in colonic temperature (Tc) of rabbits. Metabolic rate (MR) remained unchanged during the initial phase of the hypothermia for all dose groups; but peripheral vasodilation, as indicated by an increase in ear skin temperature, was seen at the higher dose levels. The observed thermoregulatory response to sulfolane was a function of Ta. Thus, at Tas of 10 and 20 degrees C, injection of 600 mg/kg sulfolane had no effect on MR but caused an increase in ear skin temperature. The magnitude of the hypothermia was similar at these two Tas, indicating the sulfolane-treated rabbits had some control over Tc. At a Ta of 28 degrees C, however, the animals became hyperthermic upon injection of 600 mg/kg sulfolane.

Animals↗

Continuous infusion or subcutaneous injection of granulocyte-macrophage colony-stimulating factor: increased efficacy and reduced toxicity when given subcutaneously.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a haematopoietic growth factor with a wide variety of applications in the clinic. In early phase I studies the continuous intravenous (c.i.) route of administration was often used. Later it was shown that subcutaneous (s.c.) administration was also effective. The optimal route of administration remains, however, poorly defined, and no studies have made a direct comparison between these two routes of administration. We treated patients with advanced breast cancer with moderately high-dose doxorubicin and cylophosphamide and GM-CSF. The first 14 patients received GM-CSF by c.i, while subsequently 47 patients received it s.c. Comparison between the two groups showed that c.i. GM-CSF was more toxic in several respects. There was a higher need for erythrocyte and platelet transfusions and a significant deterioration in the performance status. This study indicates that subcutaneous GM-CSF is the preferred route of administration. Randomised trials are, however, needed to confirm these conclusions.

Adult↗

Local tolerance of subcutaneous injections.

Human insulin-like growth factor I (hIGF-I) has several possible clinical applications. Because subcutaneous administration of the drug can cause pain, local tolerance to injection of different formulations with or without hIGF-I has been investigated in man using isotonic saline solution as reference. The formulations, made isotonic with NaCl, ranged in pH from 6 to 7 with phosphate buffer concentrations of 5 to 50 mM. The local tolerance after injection was assessed as injection pain on a visual analogue scale, pain duration and local tolerance (redness, paleness and oedema). The discomfort at the injection site was lowest with 10 mM phosphate, pH 7. Injection of buffer at pH 6 (50 mM phosphate) caused significantly more pain than using 10 mM phosphate, whereas the pain at pH 6 using 10 mM phosphate did not differ significantly from that experienced on injection of the solution at pH 7 using either 10 or 50 mM phosphate. hIGF-I itself did not seem to cause pain. We concluded that for subcutaneous injections at non-physiological pH, the buffer strength should be kept as low as possible to avoid pain upon injection. We also hypothesize that when a non-physiological pH must be used for stability reasons, a lower buffer strength enables more rapid normalization of the pH at the injection site.

Adolescent↗

Pharmacokinetics and pharmacodynamics of subcutaneous injection of long-acting human insulin analog glargine, NPH insulin, and ultralente human insulin and continuous subcutaneous infusion of insulin lispro.

To compare the pharmacokinetics/dynamics of the long-acting insulin analog glargine with NPH, ultralente, and continuous subcutaneous (SC) infusion of insulin lispro (continuous subcutaneous insulin infusion [CSII]), 20 C-peptide-negative type 1 diabetic patients were studied on four occasions during an isoglycemic 24-h clamp. Patients received SC injection of either 0.3 U/kg glargine or NPH insulin (random sequence, crossover design). On two subsequent occasions, they received either an SC injection of ultralente (0.3 U/kg) or CSII (0.3 U x kg(-1) x 24 h(-1)) (random sequence, crossover design). After SC insulin injection or CSII, intravenous (IV) insulin was tapered, and glucose was infused to clamp plasma glucose at 130 mg/dl for 24 h. Onset of action (defined as reduction of IV insulin >50%) was earlier with NPH (0.8 +/- 0.2 h), CSII (0.5 +/- 0.1 h), and ultralente (1 +/- 0.2 h) versus glargine (1.5 +/- 0.3 h) (P < 0.05) (mean +/- SE). End of action (defined as an increase in plasma glucose >150 mg/dl) occurred later with glargine (22 +/- 4 h) than with NPH (14 +/- 3 h) (P < 0.05) but was similar with ultralente (20 +/- 6 h). NPH and ultralente exhibited a peak concentration and action (at 4.5 +/- 0.5 and 10.1 +/- 1 h, respectively) followed by waning, whereas glargine had no peak but had a flat concentration/action profile mimicking CSII. Interindividual variability (calculated as differences in SD of plasma insulin concentrations and glucose infusion rates in different treatments) was lower with glargine than with NPH and ultralente (P < 0.05) but was similar with glargine and CSII (NS). In conclusion, NPH and ultralente are both peak insulins. Duration of action of ultralente is greater, but intersubject variability is also greater than that of NPH. Glargine is a peakless insulin, it lasts nearly 24 h, it has lower intersubject variability than NPH and ultralente, and it closely mimics CSII, the gold standard of basal insulin replacement.

Adult↗

Neutralization of a snake venom hemorrhagic metalloproteinase prevents coagulopathy after subcutaneous injection of Bothrops jararaca venom in rats.

Coagulopathy is one of the major complications following envenomations by crotalid and viperid snakes. The present study was undertaken to examine the effect of a hemorrhagic metalloproteinase in Bothrops jararaca venom, jararafibrase I (JF I), on the development of coagulopathy using rat snakebite model. Coagulation parameters were monitored after subcutaneous injection of B. jararaca crude venom, JF I-neutralized venom and purified JF I in rats. Crude venom induced unclottable blood and fibrinogen consumption, while JF I-neutralized venom and purified JF I did not induce coagulopathy. Plasma venom antigen level of rats given JF I-neutralized venom was lower than that of rats given crude venom. We conclude that venom hemorrhagic metalloproteinases play an important role in the development of coagulopathy through rapid spreading of venom coagulation components from the injected area into systemic circulation.

Animals↗

Serum melatonin after a single aqueous subcutaneous injection in Syrian hamsters.

A single injection of 25 micrograms melatonin was given subcutaneously in 0.1 ml saline either at 3 h into the light phase (morning) in female Syrian hamsters or at 1 h before the beginning of the dark phase (evening) in males (L/D 14/10 h). In both cases, the maximal mean serum values seen at 20 min after injection (50 ng/ml) were more than 1,000 times the normal nocturnal melatonin concentration. By 1 h after injection, serum melatonin had fallen to 10% (morning) or 4% (evening) of the respective 20-min value. The average half-times for plasma concentration during the second hour after injection were 14 min in the morning and 13 min in the evening. After either morning or evening injection, serum melatonin reached normal daytime concentration between 2 and 4 h after injection.

Animals↗

Biochemical changes in mouse lung after subcutaneous injection of the sulfur mustard 2-chloroethyl 4-chlorobutyl sulfide.

Sulfur mustard (HD) is a vesicant-type chemical warfare agent (CWA) introduced in World War I which continues to be produced, stockpiled, and occasionally deployed by some countries, and could be used potentially by terrorists. Exposure to HD can cause erythema, blisters, corneal opacity, and airway damage. We have reported previously that subcutaneous (SC) injection of immunodeficient athymic nude mice with the half mustard butyl 2-chloroethyl sulfide (BCS) causes systemic biochemical changes in several organs distal to the exposure site. In the present study, we examined the response of non-immunodeficient Swiss Webster mice to the mustard, 2-chloroethyl 4-chlorobutyl sulfide (CECBS). In a pilot study, we found that a single SC injection of 20-25 microl/mouse causes death within 24h. Consequently, we used 5 microl/mouse (approx. 0.017 mg/kg body weight) of neat CECBS or an equal volume of saline as control. We examined the lungs after 1, 24, and 48 h for biochemical changes including total and oxidized glutathione, protein, DNA, and lipid peroxidation contents in tissue homogenate, and superoxide dismutase, catalase, glucose-6-phosphate dehydrogenase, and glutathione S-transferases activities in the cytosol. After 1h and/or 24h, we found statistically significant changes that were resolved by 48 h. These changes mimicked those of HD and BCS and were generally consistent with free radical-mediated oxidative stress. The implications of these observations are two-fold. First, dermal exposure to low-dose mustard gas could elicit systemic changes impacting distal organs such as the lungs. It also suggests that antioxidants could potentially modulate the response and reduce the damage. Second, although the use of known CWAs such as HD is prohibited, analogs that are not recognized as agents are as toxic and could be dangerous if acquired and used by potential terrorists.

Animals↗

Subcutaneous injection of metallic mercury.

Deliberate self-injection of metallic mercury into subcutaneous tissue is uncommon. A 41-year-old lady with a history of schizophrenia was admitted to our hospital after deliberate injection of metallic mercury into her right wrist and antecubital fossa. Physical examination was unremarkable except for the injection marks over right antecubital fossa and wrist. The presence of subcutaneous mercury deposits in her right elbow and wrist was confirmed by X-rays and ultrasound scan. Three days later, erythema, swelling, induration and tenderness were seen over the injection sites. At the operation on day 9, mercury streaks were seen within the brachialis muscle belly, surrounded by friable necrotic tissues along the tract. A similar picture was noted in her right wrist. The necrotic tissues and mercury streaks were removed. The patient had been unco-operative and she only received incomplete treatment with dimercaprol and 2,3-dimercaptosuccinic acid. Her total blood mercury level (normal < 50 nmol/L) decreased from 101-151 nmol/L in the first two weeks to 42 nmol/L 3 months later. Her 24-hour urinary mercury excretion (normal < 10 nmol) changed from 55.7-209.5 nmol in the first 7 weeks to 125.4 nmol 3 months later. This case illustrates that soft tissue metallic mercury can produce local necrosis and may allow continuous absorption with persistent elevations in blood and urinary mercury levels. Therefore, early surgical removal of subcutaneous mercury deposits is required to prevent local complications and minimize the risk of systemic absorption and toxicity.

Adult↗

Assessment of glomerular filtration rate utilizing subcutaneously injected 51Cr-EDTA.

1. 51Cr-EDTA injected with lidocaine and epinephrine, as a subcutaneous button, is slowly absorbed, and a plasma level that is relatively stable can be maintained for a time sufficient to permit measurement of the renal clearance of EDTA, which is a measure of glomerular filtration rate (GFR). We studied this procedure in 32 normal volunteers and 24 patients with different glomerulopathies, comparing EDTA and creatinine clearances. In 20 patients these measurements were also compared with inulin clearance. 2. Creatinine clearance overestimates GFR due to tubular secretion of creatinine. This secretion is present even in patients with significantly reduced glomerular filtration rates. As a consequence, the lower the GFR the higher the overestimation will be. 3. A good correlation was obtained between the 51Cr-EDTA and inulin clearance: y(EDTA) = 4.21 + 0.88 x (inulin), r = 0.98. The procedure is simple to perform, and the radiotracer utilized is significantly less expensive than iothalamate.

Adolescent↗

Pharmacokinetic model for the absorption of subcutaneously injected soluble insulin and monomeric insulin analogues.

A subcutaneous insulin absorption model is presented for parameter estimation from the time course of plasma insulin. Modifications of a published model were made for the absorption of soluble insulin and monomeric insulin analogues in the range of therapeutic concentrations and volumes. The modified diffusion-dissociation model with distributed parameters was approximated by a multiple-compartment model. Subcutaneous absorption of soluble insulin and monomeric insulin analogues with various volumes, concentrations, and injection depths was simulated. The model for soluble insulin exhibits volume, concentration, and injection depth dependent absorption, as experimentally observed. It was found that binding of soluble insulin in the subcutaneous tissue is negligible for U-40 and U-100 strengths. The absorption of identical doses (10 U) of soluble U-40 insulin was markedly faster (T-50% = 159.4 min) than the absorption of U-100 (T-50% = 196.2 min). According to the simulation results, the absorption rate of monomeric analogues is not dependent on concentration. No significant chances of the absorption rate could also be observed by varying volume and injection depth of the monomeric analogues.

Computer Simulation↗

Prolonged survival of mice with myeloid leukemia by subcutaneous injection of recombinant human G-CSF.

We studied the effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on leukemia development and survival of mice with leukemia by using a radiation-induced myeloid leukemia cell line (C2M) with A-type phosphoglycerate kinase (PGK) as marker isoenzyme. C3H/He mice with B-type PGK were inoculated with 2 x 10(6) C2M cells through the tail vein. From the next day, they received a daily subcutaneous injection of 1 microgram rhG-CSF or control solution. The survival of rhG-CSF-treated recipients of C2M was significantly longer than control-solution-treated recipients. In rhG-CSF-treated recipients, not only spleen weight but also the number of blasts in hemopoietic organs was less than those in control recipients. While there was a remarkable decrease in bone marrow content of CFU-GM in control recipients, the content in rhG-CSF-treated recipients was comparable to that in normal mice. A reduced bone marrow and spleen content of leukemic colony-forming cells (L-CFU) was observed in rhG-CSF-treated recipients in comparison with control recipients. The electrophoretic analysis of PGK phenotypes of hemopoietic organs indicated the delayed appearance of A-type PGK from C2M cells in rhG-CSF-treated recipients. From these findings, we concluded that the injection of rhG-CSF delayed the onset of leukemia and improved the survival and several hematological parameters by suppressing C2M cells in recipient mice.

Animals↗