How to perform appropriate flushing after lipid emulsion administration using totally implantable venous access devices in long-term total parenteral nutrition and home parenteral nutrition.

BACKGROUND & AIMS: There has been no clear evidence regarding the appropriate method of flushing catheters and totally implantable venous access devices (TIVADs) after lipid emulsion (LE) administration. Therefore, the aim of the study was to identify appropriate methods of flushing to minimize residual LE when using TIVADs to ensure the safety of long-term total parenteral nutrition (TPN) and home parenteral nutrition (HPN). METHODS: A soybean oil LE containing indocyanine green (ICG) was administered from the injection site of the primary infusion set for flowing TPN, and LE dynamics were evaluated by a fluorescence imaging system. TIVADs were connected to the end of the infusion sets. After LE administration, the tubes and chambers were flushed from the injection site using saline at various speeds (20, 40, 60 mL/min), with and without pulsation. The washout effect of TPN solution after LE administration followed by flushing was examined, as was the washout effect of size differences in the infusion sets. RESULTS: When the LE was flushed with 20 mL of saline immediately after administering the LE using a standard infusion set (inner diameter 2.5 mm), the LE still remained in the tubes and chambers under any flushing condition. Flushing the LE from the injection site with 10 mL of saline and then flowing >240 mL of TPN solution were effective for minimizing residual LE inside the tubes and chambers. When using an infusion set with a small inner diameter (1.0 mm), the LE inside the tubes and chambers was almost discharged with ≥20 mL of saline immediately after administering the LE. In all settings, flushing with/without pulsation did not affect LE washout efficacy. CONCLUSIONS: Flushing immediately with saline ≥10 mL and then flowing >240 mL of primary PN solution after soybean oil LE administration using the standard infusion set or flushing with 20 mL saline immediately after administering the soybean oil LE using the infusion set with a small inner diameter are effective for minimizing the residual LE in the catheter and TIVAD, ensuring the safety of long-term TPN and HPN.

Trehalose solution protects mesothelium and reduces bowel adhesions.

BACKGROUND: Preventing interbowel adhesions still remains a challenge. Peritoneal mesothelial damage can induce postoperative adhesions. Our study evaluated the effects of 3% trehalose solution on mesothelial protection and adhesion prevention. Also, we compared this novel solution with Seprafilm regarding efficacy. METHODS: Mesothelial damage was induced on the cultured human mesothelial cell (Met-5A) and rabbit cecum-serosal surface by air-drying for 60 min, and trehalose solution was applied. Cell integrity was tested by measuring lactate dehydrogenase, and serosal-morphologic changes were analyzed using scanning electron microscopy. Intra-abdominal adhesions were induced in rabbits by the combination of abrasion and air-drying procedures. Animals were divided into four groups: control, 3% trehalose solution, Seprafilm, and 3% trehalose solution with Seprafilm. Adhesions were evaluated blindly 7 d later. RESULTS: Lactate dehydrogenase release from the Met-5A cells was reduced dose-dependently by trehalose (P < 0.05). Morphologic studies clearly showed that mesothelial cells on the serosal surface were kept intact by 3% trehalose solution. In a rabbit adhesion model, 3% trehalose solution reduced adhesions between bowel and bowel or bowel and surrounding structures (P < 0.01 versus control and Seprafilm). Seprafilm reduced adhesions between abdominal wall and underlying viscera (P < 0.01 versus control and 3% trehalose solution). Three-percent trehalose solution with Seprafilm showed additive effects of adhesion prevention, reducing adhesion formation at the previously mentioned sites. CONCLUSIONS: Three-percent trehalose solution protects mesothelial cells and leads to reduced adhesions between bowel and bowel or bowel and surrounding structures. This effect seems to be resulted from the characteristics of the solution covering most areas that potentially develop adhesions.

Imaging mass spectrometry evaluation of the effects of various irrigation fluids in a rat model of postoperative cerebral edema.

BACKGROUND: Using imaging mass spectrometry (IMS), we investigated the cerebral protective effect of an artificial cerebrospinal fluid (CSF), ARTCEREB (Artcereb, Otsuka Pharmaceutical Factory, Inc., Tokushima, Japan), as an irrigation and perfusion solution for neurosurgical procedures in a rat craniotomy model. METHODS: Wounds created in the rat cerebral cortex were continuously irrigated with Artcereb, normal saline, or lactated Ringer's solution at a steady rate for 4 hours, after which brain tissue was collected. Brain slices were prepared and analyzed using IMS. RESULTS: In tissue surrounding the injury, the signal intensity for Na adduct ions to phosphatidylcholine was high and that for K adduct ions to phosphatidylcholine was low. This is thought to reflect the level of water retention in brain cells and to be a change accompanying edema. The signal intensity with Na adduct ions to phosphatidylcholine was significantly lower in the Artcereb group than in the physiological saline or lactated Ringer's solution groups. CONCLUSIONS: IMS analysis in a rat craniotomy model indicated that the level of water retention in brain cells, calculated from the signal intensity of Na-adducted phosphatidylcholine around the wound area, was lowest in the Artcereb group, suggesting that artificial CSF that has similar composition and properties to human CSF can minimize edema in the brain surrounding the surgical wound.

Intrathecal disposition of ARTCEREB® irrigation and perfusion solution for cerebrospinal surgery in rats.

We investigated the disposition of ARTCEREB® irrigation and perfusion solution (Artcereb) during intrathecal perfusion in a lateral ventricle-cisternal perfusion model in conscious rats. In this perfusion model, the perfusion rate was set at 0.35 ml/kg/h, taking into consideration the clinical perfusion rate (500 ml/60 kg/d). The influence of Artcereb on electrolytes in cerebrospinal fluid (CSF) and blood were then investigated. After 24 h of ventriculocisternal perfusion with Artcereb using the push-pull method, output of K(+), Na(+) and Cl(-) to the cistern magna was very similar to input of these electrolytes in Artcereb infused intraventricularly. Recovery rates of K(+), Na(+) and Cl(-) after perfusion were 102%, 105% and 100% when calculated using the recovered perfusion solution. In addition, concentrations of K(+), Na(+) and Cl(-) in blood remained almost constant at near baseline levels throughout perfusion. Thus, intrathecally perfused Artcereb did not affect electrolyte balance in the CSF and blood. To confirm the dynamics of Artcereb distribution, a whole body autoradiography study was performed at 1 and 6 h after perfusion with ¹4C-inulin-added Artcereb. Radioactivity was detected in the entire CSF space of the brain, and the cribriform plate in the nasal cavity, and the cerebrospinal cavity. Radioactivity was observed in the bladder, thus suggesting that some ¹4C-inulin was transferred to the bloodstream via a physiological route, and was excreted renally.

Pharmacological assessment of ARTCEREB irrigation and perfusion solution for cerebrospinal surgery using primary cultures of rat brain cells.

ARTCEREB irrigation and perfusion solution (Artcereb), an ethical pharmaceutical, is typically applied inside the skull and spinal cavity as artificial fluid. Artcereb is composed of glucose and electrolytes (Na+, K+, Mg2+, Ca2+, Cl-, HCO3- and P) and has a pH of 7.3. An in vitro assessment of the effects of Artcereb on cell culture of rat fetal astrocytes or rat fetal brain cells was performed in comparison with normal saline and lactated Ringer's solutions. Furthermore, the effects of Artcereb on cell culture of rat fetal brain cells were also assessed in comparison with Krebs bicarbonate solution. Cell function after exposure to Artcereb was assessed based on 3H-thymidine incorporation activity. Cell function after exposure to Artcereb and lactated Ringer's solution in primary cultures of rat fetal astrocytes remained unaffected when compared to that after exposure to normal saline. Cell function after exposure to Artcereb in a primary culture of rat brain cells remained unaffected as compared to that after exposure to normal saline and lactated Ringer's solution. However, function decreased after exposure to a modified Artcereb formulation lacking bicarbonate, thus confirming that the presence of bicarbonate is essential for the Artcereb formulation.

[Pharmacological assessment of ARTCEREB irrigation and perfusion solution for cerebrospinal surgery based on glucose incorporation activity in primary cultures of rat brain cells].

ARTCEREB irrigation and perfusion solution (Artcereb) is typically used as an artificial fluid for applications inside the skull and spinal cavity. This in vitro study was conducted to assess the effects of Artcereb in cultures of rat fetal brain cells. Cell function following exposure to Artcereb was evaluated by measuring (3)H-deoxy-D-glucose incorporation activity. Cell function was significantly reduced in primary cultures of rat fetal brain cells at 0 h and 24 h after 1-h or 3-h exposure to normal saline as compared with Artcereb. Cell function was also significantly reduced at 24 h after 3-h exposure to lactated Ringer's solution as compared with Artcereb. Furthermore, cell function was significantly reduced at 24 h after 3-h exposure to a modified Artcereb formulation lacking either HCO(3)(-) or Mg(2+) as compared with Artcereb, while cell function was unaffected at 24 h after exposure to lactated Ringer's solution with HCO(3)(-) or normal saline with HCO(3)(-) as compared with Artcereb. These findings suggest the importance of the presence of HCO(3)(-) and Mg(2+) in the formulation of Artcereb.

Modulation of physiological hemostasis by irrigation solution: comparison of various irrigation solutions using a mouse brain surface bleeding model.

OBJECT: Intraoperative bleeding often obscures the surgical field and may cause neurological damage. The irrigation fluids used during surgery might affect physiological hemostasis because they modulate the extracellular fluid composition of the bleeding area directly. The authors therefore investigated the influence of irrigation fluid on hemostasis in a mouse brain surface bleeding model. METHODS: The cerebral cortices of ddY strain mice were exposed under irrigation with normal saline, lactated Ringer (LR) solution, or artificial CSF (ACF-95). To investigate the influence of electrolytes, calcium, potassium, or both were also added to the saline. After 10 minutes of irrigation at 100 ml/hour, sequential photographs of the surgical area were taken with a microscope, and the number of bleeding points was counted visually. Irrigation and counting were performed in a masked manner. RESULTS: There were significantly more bleeding points after irrigation with normal saline than with ACF-95; LR solution had a similar effect on physiological hemostasis as ACF-95. Saline augmented with calcium or potassium and calcium was superior to normal saline in terms of hemostasis. CONCLUSIONS: The authors demonstrated that the irrigation fluid used in neurosurgery affects bleeding at the surgical site. To avoid surgical site bleeding, ACF-95 and LR solution should be used as irrigation fluids instead of normal saline. The calcium and potassium content of irrigation solutions seems to be important in hemostasis.

Perfusion fluids used in neurosurgery affect cerebrospinal fluid and surrounding brain parenchyma in the rat ventriculocisternal perfusion model.

ARTCEREB, an irrigation and perfusion solution (Artcereb), is a preparation intended for the irrigation and perfusion of the cerebral ventricles, and it is therefore important to evaluate its effects on cerebrospinal fluid (CSF) and on the surrounding cerebrospinal parenchyma. To confirm the kinetics of the perfusion fluid component, we performed whole body autoradiography and examined glucose balance during ventriculocisternal perfusion with (14)C-glucose labeled Artcereb in the rat model, which simulates ventricular irrigation or ventriculocisternal perfusion in clinical neurosurgery. We also performed ventriculocisternal perfusion with Artcereb, lactated Ringer's solution, or normal saline, and observed the effect of these solutions on animal condition and on brain tissue morphology. In the kinetic study, diffusion of (14)C-glucose from the perfused Artcereb to the cerebrospinal tissue was seen on whole body autoradiography, and almost 90% of the glucose in the perfusion fluid was distributed to the cerebrospinal tissue and the systemic circulation. These data indicated that the perfusion fluid interacted actively with the CSF, surrounding parenchyma and the systemic circulation, and suggested that the formation of perfusion fluid affected CSF composition and cerebrospinal tissue functions. Animals perfused with normal saline were associated with serious symptoms including tonic convulsions and death, and exhibited neuronal death in the cerebrum. However, these severe changes were not observed in animals perfused with Artcereb or lactated Ringer's solution. We therefore propose that during neurosurgery, it is extremely important to use a physiological solution like Artcereb which closely resembles normal human CSF, in order to maintain cerebrospinal function and to alleviate postoperative adverse events.

[ARTCEREB irrigation and perfusion solution for cerebrospinal surgery: pharmacological assessment using human astrocytes exposed to test solutions].

ARTCEREB irrigation and perfusion solution (Artcereb) is a preparation intended for the irrigation and perfusion of the cerebral ventricles, and it is therefore important to evaluate the effects of Artcereb on brain cells. In vitro assessment of the effects of Artcereb in cell cultures of human fetal astrocytes was conducted in comparison with normal saline and lactated Ringer's solution. The effects of exposure to Artcereb were evaluated based on microscopic images of the mitochondria stained with rhodamine 123. The effects of exposure to Artcereb on cell function were also evaluated by quantitative analysis of mitochondrial activity based on rhodamine 123 and (3)H-thymidine incorporation. Morphological changes in nuclear structure were also evaluated. The results of the present study showed that cell function in cell cultures of human astrocytes was relatively unaffected by exposure to Artcereb as compared with normal saline or lactated Ringer's solution, suggesting that Artcereb has less effect on brain cells than normal saline or lactated Ringer's solution when used for the irrigation or perfusion of the cerebral ventricles.

Various irrigation fluids affect postoperative brain edema and cellular damage during experimental neurosurgery in rats.

BACKGROUND: This study was conducted to investigate how various irrigation fluids used during neurosurgical procedures affect the degree of postoperative brain edema and cellular damage during experimental neurosurgery in rats. METHODS: The cerebral cortex was exposed and incised crosswise with a surgical knife under irrigation with an artificial CSF, lactated Ringer's solution, or normal saline. Four hours after injury, irrigation was stopped and brain tissue samples were obtained from injured and uninjured sites. Specific gravity, cerebrovascular permeability, and TTC staining of the samples were evaluated. Incision and irrigation of the brain were not performed on the control group. RESULTS: At the injured site, specific gravities of the samples in the normal saline group and the lactated Ringer's solution group were significantly lower than the specific gravity in the artificial CSF group. The EB concentration was significantly higher in the lactated Ringer's solution group and relatively high in the normal saline group as compared with the artificial CSF group. TTC staining did not differ significantly between the artificial CSF group and the control group. It was significantly lower in the lactated Ringer's solution group and the normal saline group than in the control group and the artificial CSF group. CONCLUSIONS: As compared with normal saline and lactated Ringer's solution, artificial CSF reduced postoperative brain edema, cerebrovascular permeability, and cellular damage in sites injured by experimental neurosurgery in rats.