A novel percutaneous barrier device that permits safe subcutaneous access.

Successful subcutaneous access is important for optimal management of internal artificial organs and treatment of many diseases. However, skin downgrowth and tissue infection are still significant problems in the use of devices that require long-term subcutaneous access. The authors developed a new percutaneous device that provides a unique biologic boundary with surrounding connective tissue while minimizing the risk of complications. This new percutaneous device is made of a circumferential, strong, thin, and flexible mesh collar with millimeter size holes for connecting the structure. It has two distinct functional portions: a connecting zone and a sealing line. The most important features of the structure are: 1) Connective tissue grows through the millimeter size pores of the connecting zone to form a strong bond between the device and healthy tissue. 2) The millimeter size pores of the connecting zone allow capillaries to grow through its entire surface, ensuring sufficient blood supply. 3) The tissue of the connecting zone and the device surface form a biosealed junction (sealing line). This sealing line is protected by the connecting zone and is free from external forces acting on local skin. 4) The device is generally functional immediately after surgical implantation. The subcutaneous perimeter of the functional dome contains extruded rigid rings of millimeter size holes permitting growth of subcutaneous tissue through the device. This functions as the minor connecting structure of the device. Four of five implanted rabbits have remained healthy 8 months postimplantation without antibiotic administration. The fifth rabbit died 4 months postimplantation for reasons unrelated to the device. Gross or histopathologic inspection revealed no signs of tissue injury or inflammation. Growth of healthy connective tissue was clearly observed. These results indicate this percutaneous device can provide a strong, stable, and effective connection to internal organs without bioboundary damage, skin downgrowth, or tissue infection.

Maintaining normal intracranial pressure in a rabbit model during treatment of severe diabetic ketoacidemia.

Increased intracranial pressure (ICP) resulting in death or neurologic morbidity continues to complicate traditional management of diabetic ketoacidemia (DKA) in pediatric patients. When ICP or cerebrospinal fluid pressures have been measured, correction of hyperglycemia in animals and treatment of DKA in humans have consistently resulted in pathologic increases in ICP. We hypothesized that elevations in ICP can be minimized if changes in effective osmolality (Eosm) are controlled during treatment of DKA. During a six-hour study period, three groups of rabbits were studied: a normal control group of nondiabetic animals (Cnor, n = 10), a control group of animals with DKA (CDKA, n = 8), and an experimental group of animals with DKA (EDKA, n = 8). There was no significant difference between the two groups with DKA regarding pretreatment degree of dehydration, blood pressure, hyperglycemia, acidemia or ICP. During the treatment period, Cnor received maintenance fluids only. CDKA received insulin and an assumed volume of deficit (150 ml/kg) along with maintenance fluids and urinary output replacement with 0.45% NaCl. EDKA received insulin and one-half the volume of deficit calculated by the weight lost with 0.9% NaCl plus maintenance fluids. There was no significant difference between CDKA and EDKA regarding the rate at which DKA was corrected. While CDKA demonstrated a progressive and statistically significant increase in ICP, EDKA exhibited no such increase in ICP compared to normal, nondiabetic controls (Cnor) during treatment. Changes in Eosm during treatment in CDKA compared to Cnor and in CDKA compared to EDKA were significantly greater (p < .01), however, changes in EOSM in EDKA compared to Cnor were not significant. These data support the clinical observation that decreasing EOSM during treatment of DKA is associated with increased ICP and suggest that DKA can be treated effectively with i.v. fluids and insulin without increasing ICP.

Physiologic management of diabetic ketoacidemia. A 5-year prospective pediatric experience in 231 episodes.

OBJECTIVE: To determine whether gradual rehydration in moderate and severe diabetic ketoacidemia (DKA) can safely prevent untoward declines in calculated effective osmolality (Eosm) early in treatment and, hence, help prevent major central nervous system complications. DESIGN: Prospective study. SETTING: Three tertiary care hospitals. PATIENTS: Two hundred thirty-one consecutive episodes of DKA in 149 patients aged 10 months to 20 years admitted during a 5-year period. INTERVENTIONS: Insulin therapy in addition to rehydration using an estimated volume of deficit with planned administration over 48 hours; initial administration of rehydration solutions with an osmolality approximating that of the patient; and intensive patient monitoring. MEASUREMENTS: Mean lowest calculated Eosm (EosmL) during the first 24 hours of treatment; trend of the concentration of sodium in serum in the first 12 hours of treatment; comparison of pretreatment serum concentrations of glucose, urea nitrogen, and corrected sodium between mildly and very severely dehydrated patients; and patient outcome. RESULTS: A mean (+/- SD) EosmL of 285.8 +/- 10.5 mOsm/kg Nater and an increase in the concentration of sodium in serum in 90% of episodes were documented. There were statistically significant differences in serum concentrations of glucose, urea nitrogen, and corrected sodium in mildly vs very severely dehydrated patients. There were no deaths or near-death episodes. CONCLUSIONS: Management of moderate and severe DKA with a 48-hour planned rehydration is safe and prevents untoward declines in Eosm. Coupled with intensive monitoring, gradual rehydration can protect against life-threatening increases in intracranial pressure and brain herniation.

Brain osmoregulation during extreme and moderate dehydration in a rat model of severe DKA.

To determine if osmoprotective molecules accumulate in the brain during severe DKA with extreme (DKA-E) and moderate (DKA-M) dehydration, Fischer 344 rats (250-350g) were given STZ 45 mg/kg (i.p.) and allowed food and water ad lib. DKA-M received NaCl 77 mmol/L 60 ml/kg (i.p.) q 4 hrs. on day 2. All rats were anesthetized and sacrificed at 48 hrs. Half of each brain was used to measure water content (BWC) and half to measure Na+, K+, and organic osmoles by HPLC. Just prior to expiration, values for mean concentration of serum glucose (mmol/L) percent weight loss and median blood pH for DKA-E were 33.4, 19%, 6.98; for DKA-M, 16.8, 7.5% and 6.84, respectively. Means +/- SEM were compared by Student's t-test. Percent BWC was 76.3, 77.3 and 77.6 in DKA-E, DKA-M and normal controls, respectively (NS). Brain Na+ and K+ were increased in DKA-M compared to controls (p < .05) but not significantly different in DKA-E compared to controls. Of organic osmoles measured (umol/g wet weight) taurine was significantly increased (p < .01) in DKA-E and DKA-M (8.04 +/- .39 and 9.73 +/- .78, respectively) as compared to controls (5.92 +/- .35) as was myoinositol in DKA-E compared to controls (9.96 +/- .39 vs. 8.87 +/- .28) (p < .05) and urea in DKA-E as compared to controls (14.24 +/- 3.9 vs. 4.14 +/- .52) (p < .01). DKA-M were not significantly different for brain myoinositol or urea as compared to control animals. There was no significant difference in brain glutamine between either study group and controls. Preservation of brain water despite systemic dehydration can be partly explained by increased brain concentrations of osmoprotective molecules. Such adaption in the clinical setting of DKA warrants a cautious repair of dehydration and hyperosmolality.

Minimizing the risk of brain herniation during treatment of diabetic ketoacidemia: a retrospective and prospective study.

We studied retrospectively, 219 episodes of diabetic ketoacidemia in 119 patients aged 13 months to 30 years, to determine the trend of the concentration of sodium in serum as glucose declined during treatment of uncomplicated episodes and of episodes with complications attributable to brain swelling. Of 20 complication, 13 were minor (headache only) and 7 major (death or near death). The concentration of sodium in serum failed to rise as that of glucose declined in 82 (54%) of 164 uncomplicated episodes and in 18 (95%) of 20 complicated episodes (p less than 0.01). Hence complications were more likely to occur among patients with a failure of the concentration of sodium to rise as glucose declined. Fifty-eight episodes of diabetic ketoacidemia in 40 patients aged 1 1/2 to 20 years were then studied prospectively on a 48-hour treatment plan to provide the volume of deficit evenly, with half the deficit of sodium in the first 42 hours. Sodium concentration in serum rose in 55 (95%) of 58 episodes as that of glucose declined. No patient had a major complication. We conclude that failure of the sodium concentration measured in serum to rise as glucose concentration declines is a marker for excessive administration of free water. An expanded repair period, with repair fluid containing an average of 125 mmol/L Na+ early in therapy, will usually protect against a downward trend in the concentration of sodium in serum and therefore against a rapid decline in effective serum osmolality. This regimen may be protective against near-death episodes and brain herniation during treatment.

Familial glucocorticoid deficiency in a girl with familial hypophosphatemic rickets.

Familial glucocorticoid deficiency is a rare multisystem disorder characterized by glucocorticoid deficiency with normal mineralocorticoid activity, achalasia of the cardia, and alacrima. Familial hypophosphatemic rickets is characterized by selective renal phosphate wasting with subsequent hypophosphatemia and an inappropriately low 1,25-dihydroxyvitamin D concentration for the degree of hypophosphatemia. A 6-year-old girl with both disorders is described. A biochemical relationship between familial glucocorticoid deficiency and familial hypophosphatemic rickets could not be defined; the influence of cortisol on her serum calcium level, phosphorus level, and rickets, as well as the natural history of these two entities, is described.