Fentanyl: clinical use as postoperative analgesic--epidural/intrathecal route.

The administration of epidural and intrathecal opioids for the management of postoperative pain is well established. Fentanyl, because of its greater lipophilicity, offers a number of advantages over morphine for epidural analgesia, including a lower incidence of side effects and reduced risk of delayed-onset respiratory depression. The relatively short duration of action of epidural fentanyl makes this agent more ideally suited for continuous infusion or patient-controlled epidural analgesia (PCEA). The effective doses and adverse effects profile of epidural fentanyl are reasonably well understood. Because of the lack of spread through the cerebrospinal fluid (CSF) and hence the segmental nature of the analgesia achieved, location of epidural catheter placement is of paramount importance when this agent is used. Prolonged epidural infusion of fentanyl may result in high systemic concentrations not dissimilar to IV infusion, and, therefore, the greatest efficacy of epidural fentanyl administration may be in combination with low concentrations of bupivacaine, an approach that achieves a synergistic effect. 2-Chloroprocaine has been shown to antagonize epidural fentanyl analgesia. Intrathecal fentanyl for postoperative analgesia is limited by its short duration of action with single-bolus administration. The widespread international increase in the use of epidural fentanyl for postoperative analgesia promises further improvements and refinement in techniques.     

Opioids: clinical use as anesthetic agents.

Opioids (narcotic analgesics) are widely used in the practice of anesthesia for preanesthetic medication, systemic and spinal analgesia, supplementation of general anesthetic agents, and as primary anesthetics. The last use is particularly widespread for major surgical operations, especially those involving patients with cardiovascular disease. The use of opioids in anesthetic doses is based on the absence of cardiac depression by the opioids. As with all anesthetic drugs, the opioids have limitations and side effects, but for the most part, these are easily managed on the basis of knowledge of their pharmacology. The key to their efficient use is careful titration of dose according to the individual patient's responses to the drug as well as to noxious stimulation. Although there is a very wide margin of safety, allowing administration of enormous doses intraoperatively when the patient's ventilation is supported mechanically, the disadvantage of using doses far in excess of the individual patient's need is a prolonged recovery from anesthesia with the risk of postoperative ventilatory depression. Titration of the dose can be facilitated by computer-controlled infusion pumps with the benefit that the recovery time from anesthetic doses can be appropriate for the individual patient and surgical procedure, and postoperative analgesia can be continued by patient-controlled analgesia, which is another example of computer-controlled opioid infusion. Although specific opioid antagonists are available, their use to antagonize residual anesthetic effects is potentially hazardous.     

The intrathecal humoral immune response: laboratory analysis and clinical relevance.

In normal conditions, albumin and immunoglobulin (Ig)G in the cerebrospinal fluid (CSF) originate from the blood, and there is no antibody production within the central nervous system. Up to 20% of CSF proteins are intrathecally synthesized, but the major fraction is blood-derived. The CSF/serum albumin quotient (QAlb) is the best marker of the blood-CSF barrier function. The corresponding immunoglobulin quotients (QIGG, QIGA, QIGM) are not linearly related to QAlb and their correlations are defined by an hyperbolic equation. This equation is used to discriminate between a blood-derived and a locally produced fraction of immunoglobulins in case of an intrathecal humoral immune response. The detection of CSF-specific oligoclonal IgG is more sensitive than the quantitative comparison between QIGG and QAlb. A further step is the determination of antibody indices and the detection of specific oligoclonal antibodies by antigen-driven immunoblots. CSF analysis remains a cornerstone for the diagnosis of various neurological disorders, including multiple sclerosis and infectious diseases of the central nervous system.     

Incidence and characteristics of naloxone use in postoperative pain management: a critical examination of naloxone use as a potential quality measure.

The administration of naloxone may be an important monitor of the quality and safety of postoperative pain management. However, studies that support the use of naloxone as a quality measure are absent. The purposes of this study are to determine the incidence and factors associated with naloxone administration in the postoperative setting and to critically examine naloxone as a potential quality measure. Participants included all postoperative adult inpatients at an academic hospital who received naloxone and an equal number of matched control patients who did not receive naloxone during the calendar year 2003. Medical record audits were performed to examine patient demographics, relevant medical history, postoperatively administered analgesics and central nervous system depressants, documented sedation and respiratory assessments, reason provided for naloxone administration, and patient outcome. Naloxone was administered to .53% (56/10,511) of all adult inpatient postoperative patients. Patients who received naloxone were significantly older and received more central nervous system depressants than cohorts. No significant differences were found in comorbidities, route of opioid administration, or amount of opioids taken by the two groups. Reversal of excessive opioid-induced sedation was the primary reason provided for naloxone administration. However, 25% of the patients were later determined to have a new diagnosis that contributed to sedation. Examination of naloxone administration proved useful in uncovering deficits in structures and processes of care. However, caution is warranted when using naloxone as a quality measure to avoid the implication that higher use indicates opioid analgesic over-treatment or error.     

Quinolones: clinical use and formulary considerations.

Quinolones are broad-spectrum antibiotics active primarily against aerobic gram-negative organisms. All quinolones have activity against oral anaerobes, but only trovafloxacin provides coverage against Bacteroides fragilis, the primary anaerobe of the abdomen/pelvis. In addition, quinolones are very active against atypical pulmonary pathogens, e.g., Legionella, but trovafloxacin is the least active against Chlamydia. As with other antibiotics, the selection of quinolones depends not simply on the degree of microbiologic activity but also on safety profile and cost. Ciprofloxacin and trovafloxacin are associated with central nervous system side effects. Photosensitivity reactions may occur with sparfloxacin. Trovafloxacin is associated with more adverse reactions than any other quinolone, and its gastrointestinal side effects are most frequent among the quinolones. Resistance potential is highest with ciprofloxacin and lowest with levofloxacin. Sparfloxacin and grepafloxacin are available only as oral formulations. Among the parenteral quinolones, ciprofloxacin and trovafloxacin are the most expensive, levofloxacin, the least expensive. Levofloxacin is preferred for general use alone or in combination because it has virtually no side effects, induces no resistance, and is the least expensive and most versatile quinolone currently available.     

Simple screening technic to estimate postoperative narcotic use.

The General Health Questionnaire, a 30-item, self-response inventory, identified individuals who required significantly more pain medication after elective cholecystectomy. The questionnaire is well tolerated by surgical patients and is easy to score. It can identify those individuals prone to request excessive narcotic medication postoperatively.     

Use of 2-hydroxypropyl-beta-cyclodextrin as an intrathecal drug vehicle with opioids.

2-Hydroxypropyl-beta-cyclodextrin (CDEX), a seven-membered glucose pyranose structure, forms reversible inclusion complexes with the lipophilic portion of a drug molecule by noncovalent bonding. This can increase the water solubility of lipid-soluble drugs and reduce the rate of clearance of such agents from the spinal cord into the vasculature after i.t. administration. In this study, opioids (morphine, lofentanil, alfentanil and sufentanil) with and without CDEX (20, 2, 0.2 and 0.02% w/v in sterile water) were administered spinally in rats prepared with chronic i.t. catheters. CDEX prolonged the duration of analgesia (52.5 degrees C hot plate) and reduced the incidence of catalepsy otherwise produced by a supermaximal i.t. dose of each of the opioids. The magnitude of the potentiating effect of CDEX on opioids was dependent upon concentration of the CDEX and varied with drug lipid partition coefficients. The highest concentration of CDEX alone (20%) had no effect upon the volume-evoked micturition reflex, blood pressure, heart rate, or spinal reflexes. Our data indicate that CDEX may be a useful i.t. vehicle for modifying the redistribution characteristics of highly diffusible molecules after their i.t. administration, and that for each drug there is an optimal CDEX concentration. In the present case, CDEX prolongs the spinal analgesic action and reduces the supraspinal actions of i.t. drugs.     

Therapeutic use of assistive technology: a clinical perspective.

Healthcare providers involved in patient handling activities are at risk for injury. One solution to minimize this risk is the use of assistive equipment. However concern exists that use of assistive equipment may minimize the rehabilitation potential of patients compared to using manual handling skills and other traditional techniques. Practical examples are provided of how typical assistive equipment can actually enhance patient rehabilitation while also preventing caregiver injury.     

Preclinical and clinical perspectives on the use of estramustine as an antimitotic drug.

A variety of cell biological, pharmacological, crystallographic and clinical approaches have indicated that the antimitotic drug estramustine has interesting and unusual properties. Although designed as an alkylating agent, the marked stability of the carbamate linkage to the steroid carrier molecule prevents the formation of alkylating intermediates. The affinity of the parent molecule for microtubule associated proteins and the concomitant antimicrotubule activity have cytotoxic consequences in tumor cells. Both preclinical and clinical studies of estramustine in combination with other antimicrotubule agents have shown that this approach has great potential to achieve therapeutic advantage, especially in disease states such as hormone refractory prostate cancer.     

The vagina as a route for systemic drug delivery.

Exhaustive efforts have been made toward the administration of drugs, via alternative routes, that are poorly absorbed after the oral administration. The vagina as a route of drug delivery has been known since ancient times. In recent years, the vaginal route has been rediscovered as a potential route for systemic delivery of peptides and other therapeutically important macromolecules. However, successful delivery of drugs through the vagina remains a challenge, primarily due to the poor absorption across the vaginal epithelium. The rate and extent of drug absorption after intravaginal administration may vary depending on formulation factors, vaginal physiology, age of the patient and menstrual cycle. Suppositories, creams, gels, tablets and vaginal rings are commonly used vaginal drug delivery systems. The purpose of this communication is to provide the reader with a summary of advances made in the field of vaginal drug delivery. This report, therefore, summarizes various vaginal drug delivery systems with an introduction to vaginal physiology and factors affecting drug absorption from the vaginal route.     

The use of chlorhexidine/n-propyl gallate as a urine preservative.

OBJECTIVE: Ambient-temperature storage of urine samples would increase the variety of life sciences studies that could be performed during spaceflight. The purpose of this study was to evaluate a preservative that would reduce the effects of oxidation and bacterial contamination on sample integrity and would be safe for personnel. DESIGN: Chlorhexidine, a topical antiseptic, and n-propyl gallate, an antioxidant used in food production, were used in combination to produce a preservative (CPG) that meets these criteria. Urine pools were prepared and divided into three aliquots that were stored unpreserved at either -70 degrees C or room temperature (21 degrees C to 25 degrees C), or stored preserved with CPG at ambient temperature. Analyte measurements were conducted on days 1, 14, and 28, and monthly thereafter for one year. Stability was defined as the ability of a test condition to result in analyte values within the acceptable range established with the reference condition (-70 degrees C). RESULTS: CPG effectively maintained stability of ammonia for 14 days, total nitrogen and 3-methylhistidine for three months, chloride for four months, sodium for five months, potassium for seven months, and urea for 12 months. Creatinine and osmolality were not preserved by CPG. CONCLUSION: These data indicate that CPG offers prolonged room-temperature storage for multiple urine analytes, reducing the requirements for frozen urine storage on future spaceflights. In medical applications on Earth, this technology can allow urine samples to be collected in remote settings and eliminate the need to ship frozen samples.     

SADE database for endoscopic procedures: aspects of clinical use.

The time aspects of daily use of a clinical database system in an endoscopy department were studied. The SADE database system for endoscopic procedures was introduced for daily use at Ullev?l Hospital on 1 January 1989. The average weekly programme of the endoscopy unit includes 57 gastroduodenoscopies, 23 colonoscopies and 12 ERCP/EPTs. During three consecutive weeks of the study the mean physician input time was 4 min 17 sec per patient (range 57 sec to 15 min), individual variation depending mainly on the extent of the report. Assistants spent a mean time of 4 min 23 sec for each patient. Thus, a total of 8 min 40 sec was spent for every patient seen. Endoscopic units should analyze their routines and needs before introducing an electronic data base manager.