The true epidural space: possible consequences for administered material-based drug delivery systems.
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Drug Delivery Systems↗
Biomedical subjects
H H Korsten
Publications and source records attributed to H H Korsten.
Butyl-p-aminobenzoate. Preparation, characterization and quality control of a suspension injection for epidural analgesia.
The conditions for the preparation of a 10% butyl-p-aminobenzoate suspension for epidural administration were investigated. Pharmaceutically acceptable suspensions are composed of butyl-p-aminobenzoate particles dispersed in a solvent consisting of the surfactant polysorbate 80 added to normal saline in a concentration of 0.25 mg/ml. pH Correction is not necessary. The suspensions are sterilized at 120 degrees C followed by special milling procedures to accomplish acceptable particle size. Butyl-p-aminobenzoate suspensions are stable at 4 degrees C during a period of at least four weeks.
Analgesics↗
Long-lasting epidural sensory blockade by n-butyl-p-aminobenzoate in the terminally ill intractable cancer pain patient.
An aqueous suspension of n-butyl-p-aminobenzoate (BAB), a highly lipid-soluble congener of benzocaine, was applied epidurally in terminally ill cancer patients with intractable pain. The suspension consisted of 10% BAB and 0.025% of the nonionic surfactant polysorbate 80 in 0.9% sodium chloride. Twelve consecutive patients received epidural BAB because pain was uncontrollable either by palliative radiotherapy or oral or epidural administrations of analgesics. The catheter or injecting needle was positioned at the segmental level of the pain. Repeated epidural injections were administered. In all patients, long-lasting sensory blockade (segmental analgesia) occurred, accompanied by a marked reduction or even absence of pain. In all patients, treatment with epidural opioids, alone or combined with local anesthetics, was no longer necessary. Five of the 12 patients did not require further administration of oral opioids. Motor, bowel, and bladder function were well preserved. In 6 patients, extensive necropsy of the spinal cord and spinal nerves did not reveal pathomorphologic changes. The outer aspect of the dura showed signs of focal necrosis on microscopy, yet its collagen structure and thickness were unchanged. Epidurally, focal infiltrative reactions were seen. The epidural use of an extremely lipid-soluble--hence hydrophobic--local anesthetic, with an exceptionally low pKa (2.3), formulated in suspension of the base, is conceptually innovative and needs further investigation. The authors conclude that the epidural administration of a BAB suspension may be an effective alternative to the neurolytic agents alcohol and phenol and may replace procedures such as cordotomy. Further investigation to determine the safety of BAB in this patient group appears warranted.
Adult↗
Long-lasting epidural sensory blockade by n-butyl p-aminobenzoate in the dog: neurotoxic or local anesthetic effect?
An aqueous suspension of n-butyl p-aminobenzoate (BAB), a highly lipid-soluble congener of benzocaine, was applied epidurally and around ulnar nerves in dogs. The suspension consisted of 10% BAB and 0.025% polysorbate in 0.9% NaCl. Sensory effects were tested by electrical stimulation. Three epidural injections were given, and the dogs were killed after 21 days. The increase in stimulation threshold was comparable to the effect of lidocaine in a concentration between 0.5% and 1%. Increased sensory threshold lasted for days, whereas no long-lasting motor effects were observed. Pathomorphologic changes were found primarily in the dorsal spinal nerve roots, although slight changes were also found in the ventral spinal roots. White matter degeneration was found only in the lumbar dorsal columns. This result suggested Wallerian degeneration in the dorsal spinal nerves and was at variance with recently published data on epidural BAB. No changes were observed in the ulnar nerves. The authors demonstrated that the pathomorphologic changes were induced by the BAB suspension and not by the suspending additive polysorbate 80. It was postulated that the suspension of BAB, which contains particles of a median size of 15 microns, was mainly confined to the dorsal epidural space where neurolytic changes in axons of the dorsal spinal nerve roots and dorsal columns are induced. This may explain the long-lasting sensory effects seen in intractable cancer pain patients after epidural BAB administration. More research is necessary to define the distribution of BAB in nervous tissue after its epidural administration and to better characterize toxicity, neurolytic effects, and regeneration of nervous tissue after BAB administrations.
Analgesia, Epidural↗
Pulmonary shunting after cardiopulmonary bypass.
The effect of cardiopulmonary bypass (CPB) on pulmonary function was investigated in 32 adult patients, including 23 patients undergoing coronary artery bypass grafting and nine patients undergoing heart-valve replacement. Clinical indicators for pulmonary insufficiency, such as chest X-ray, gas exchange and lung function tests were measured. Transthoracic electrical impedances were measured, and the mean specific thoracic impedance (RHO) was calculated. (RHO is an accurate indicator for the intrathoracic fluid content; low RHO values correspond with high intrathoracic fluid content.) Significant postoperative decreases in RHO were paralleled by a significant impairment of gas exchange. Chest X-rays demonstrated accumulation of intrathoracic fluid. Lung function tests showed significant postoperative decreases in lung volumes and vital capacity. These findings are consistent with the concept that CPB provokes an inflammatory reaction in the lung. The non-invasive RHO measurement proved to be simple and in good agreement with clinical indicators. This method may be a real asset in the prevention and treatment of pulmonary dysfunction after CPB. The possibility of calibrating RHO with respect to absolute values of intrathoracic fluid content should be investigated.
Cardiography, Impedance↗
Emergency aortic valve replacement in the 24th-week of pregnancy.
The incidence of heart disease during pregnancy has declined from 3.6% to approximately 1.5% over the last 25 years as a result of better medical and surgical care. Rheumatic heart disease still accounts for 75% of cases and the incidence of bacterial endocarditis during pregnancy is about 1 in 8000. Seaworth and Durack reviewed 124 cases found in the literature of a 40 year period. The experience of any anesthetist with such cases will thus be limited. In this case report a patient is described who required emergency aortic valve replacement in the 24th week of pregnancy. The effect of the non-pulsatile flow during the extracorporeal circulation on the foetal unit will be discussed. Recommendations for the perioperative management include a normothermic high flow, high pressure perfusion technique, monitoring of foetal heart rate and uterine activity and vigorous tocolysis using beta sympathomimetics and progesterone.
Acute Disease↗
Aortic valve replacement in the second trimester of pregnancy: a case report.
A 36 year old woman with left heart failure and right-sided hemiparesis due to endocarditis of the aortic valve underwent urgent aortic valve replacement during the 24th week of gestation. High-flow high-pressure normothermic perfusion during cardiopulmonary bypass was performed. Peri-operative fetal heart rate and uterine contractions were monitored. Severe fetal heart rate decelerations and loss of variability as well as uterine contractions were observed during surgery. Uterine contractions were treated medically. Pregnancy was carried to term and a healthy baby was delivered vaginally. The effect of the nonpulsating cardiac pump during extracorporeal circulation on the fetus will be discussed. Recommendations for the peri-operative management of the fetal unit are made.
Adult↗
Observations on blood flow related electrical impedance changes in rigid tubes.
Mammalian blood in pulsatile flow through a rigid tube has been shown to be anisotropic with regard to its electrical conductivity. When flow increases there is a rise in conductivity in the longitudinal and a fall in the radial direction. These changes are caused by flow-dependent variations in the orientation of the disk-shaped erythrocytes.
Animals↗
GASTON: an architecture for the acquisition and execution of clinical guideline-application tasks.
Recently, studies have shown the benefits of using clinical guidelines in the practice of medicine. There have been numerous efforts to develop clinical decision support systems that support guideline-based care in an automated fashion, covering a wide range of clinical settings and tasks. Despite these efforts, only a few systems progressed beyond the prototype stage and the research laboratory. For guideline-based clinical decision support systems to be successful, a balance must be made between intuitive but imprecise representations usually encountered by most of today's systems and representations that support a strong underlying clinical performance model. The project described in this paper tries to achieve such a balance. It presents the GASTON architecture that contains a set of reusable software components for the application of guidelines, including design-time components to facilitate the guideline authoring process based on guideline representation models along with execution-time components for building decision support systems that incorporate these guidelines. This architecture was used to develop several guideline representation models such as a rule-based representation to model rule-based guidelines and guideline representation models that address more complex tasks. Also, decision support systems that incorporate these models were developed with the architecture. For the representation and application of various classes of guidelines, rules were also viewed as instances of more complex tasks. By identifying similar characteristics of sets of rules, we developed several tasks such as a drug intera ction and drug contraindication task. Based on these models, we have developed and validated guidelines and decision support systems for use in several application domains such as intensive care, family physicians and psychiatry. In order to be able to represent more complex time-oriented plans, new guideline representation models are being developed.
Algorithms↗
Spinal anesthesia. Volume or concentration--what matters?
BACKGROUND AND OBJECTIVES: An investigation was made of the effects of volume and concentration of a constant dose of subarachnoid lidocaine on the extent and duration of sensory and motor anesthesia produced, as well as of the lidocaine concentration of the cerebrospinal fluid (CSF) as a function of time. METHODS: In a prospective study, 40 American Society of Anesthesiologists (ASA) status 2 or 3 patients were assigned to one of five groups, who received a 70-mg subarachnoid dose of lidocaine hydrochloride as a 0.5, 1, 2, 5, or 10% solution. Dural puncture was performed at the L3-L4 interspace with a 19.5-gauge Periquick needle (Pajunk, Germany), and a 24-gauge catheter was inserted 3-4 cm into the subarachnoid space. The patient remained in the lateral position during injection of the local anesthetic and was then turned to the supine horizontal position. The level of anesthesia and the motor block were measured at 5, 10, 15, 20, 30, 40, 50, and 60 minutes and then at 15-minute intervals until the effect of the anesthesia had ceased. Samples of CSF were collected at the same times that the pinprick and motor block measurements were made. RESULTS: Five minutes after injection, a median sensory block height of T4 or T5 was observed in all groups. The range of mean total times to complete recovery of the sensory blocks was 139-152 minutes, while that for the motor blocks of the lower extremities was 100-122 minutes. The values were similar in all groups (P > .05). The motor block was complete in all patients 10 minutes after the lidocaine injection. Five minutes after injection, the mean CSF lidocaine concentration was highest in the 10% group (P < .001 vs. the other four groups). At 15 minutes, the only statistical difference was found between the 0.5% and the 10% group (P = .026). At 20 minutes, the CSF lidocaine concentrations were similar in all groups (P > .05). CONCLUSIONS: A constant 70-mg dose of subarachnoid lidocaine produced the same pinprick level of analgesia, degree of motor block, and duration of spinal anesthesia in spite of being injected over an extremely broad range of concentrations and volumes. Despite the fact that all patients received the same dose of lidocaine, the CSF concentrations at 5, 10, and 15 minutes were different and directly related to the concentration of the solution injected. at 20 minutes, the CSF concentrations were similar in all groups. These results indicate a relatively uniform distribution of lidocaine in the CSF for all solutions tested.
Aged↗