Tobramycin pharmacokinetics in morbidly obese patients.

Tobramycin kinetics were examined in 9 morbidly obese women following a single intravenous (120 mg) bolus. After the injection, serum elimination conformed to a 2-compartment open model with alpha and beta t1/2s of 0.285 and 2.1 hr. The volume of distribution (Varea) was determined to be 0.44 1/kg ideal body weight (IBW) and 0.20 1/kg total body weight (TBW). To normalize Varea to 0.26 1/kg, 58% of the patients' adipose weight (TBW -- IBW) must also be taken into account.

Cytomegalovirus colitis after 5-fluorouracil and interferon-alpha therapy.

Cytomegalovirus (CMV) infection is an opportunistic viral infection primarily affecting immunocompromised patients. Patients with inflammatory bowel disease have an increased risk for developing CMV infections of the gastrointestinal tract. While receiving continuous infusion of 5-fluorouracil and interferon-alpha, a 72-year-old woman with stage IV pancreatic carcinoma developed severe colitis with diarrhea that was refractory to conventional antidiarrheals. A biopsy specimen from the colon revealed CMV inclusions, which were confirmed by immunofluorescence. The patient was given ganciclovir 210 mg (5 mg/kg) every 12 hours for 14 days, and the diarrhea resolved after approximately 8 days of therapy. This is the first reported case of CMV colitis associated with combination 5-fluorouracil and interferon-alpha therapy.

Impact of antiemetic selection on postoperative nausea and vomiting and patient satisfaction.

STUDY OBJECTIVE: To determine the impact of antiemetic selection on postoperative nausea and vomiting (PONV) and patient satisfaction after ambulatory surgery. DESIGN: Prospective, observational study. SETTING: Ambulatory surgery center in an academic medical center. PATIENTS: Five hundred fifty-four consecutive patients undergoing ambulatory surgical procedures of any kind. INTERVENTION: Data on antiemetic utilization, occurrence of PONV, and patient satisfaction were collected perioperatively. Multiple regression analyses for antiemetic choice were performed. MEASUREMENTS AND MAIN RESULTS: Prophylactic antiemetic therapy was administered to 292 (52.7%) patients, most often with droperidol (200 patients), metoclopramide (134), or dexamethasone (55). Forty-one (7.4%) patients had an episode of emesis in the postanesthesia care unit. Choice of antiemetic was not a significant predictor of PONV. Patient satisfaction for all patients was 9.5 on a 10-point scale, with no agent more or less successful than any other. CONCLUSION: As choice of antiemetic drug given for prophylaxis had little impact on clinical outcome or patient satisfaction, traditional agents should form the core of antiemetics used for PONV prophylaxis in ambulatory surgery patients.

Comparison of urinary urea nitrogen excretion and measured energy expenditure in spinal cord injury and nonsteroid-treated severe head trauma patients.

Severe head trauma patients (HT) exhibit markedly elevated energy expenditure and 24-hr urinary urea nitrogen excretion (UUN) values. The objective of this study was to compare seven spinal cord injured patients (SCI) to seven HT for changes in UUN and measured energy expenditure (MEE) over the first 18 days following injury. Energy expenditure was measured by indirect calorimetry and compared to values predicted by the Harris Benedict Equation (PEE). There were six quadriplegics and one paraplegic in the SCI group. HT patients had peak Glasgow Coma Scale scores of 3 to 10 for the first 24 hr postinjury. Patients were studied prospectively and matched for age, sex, and admitting weight Week 1 following the injury, SCI had mean UUN values of 0.18 +/- 0.04 g/kg/day vs 0.18 +/- 0.01 for HT patients. The mean MEE/PEE ratio was 0.56 for the SCI and 1.4 for HT (p less than 0.01). Over the entire study period the mean UUN value for SCI was 0.23 +/- 0.03 g/kg vs 0.21 +/- 0.01 for HT. The mean MEE/PEE ratio for SCI was 0.94 while HT remained elevated at 1.5 (p less than 0.05). Although the UUN was comparable in SCI vs HT, there was a significant difference in MEE/PEE between the groups. The elevation in UUN observed in SCI is not due to a hypermetabolic state. This suggests that different mechanisms promote the increased nitrogen excretion observed in these two populations.

Implementation of a criteria-based antimicrobial formulary system.

The development of a criteria-based antimicrobial formulary system for use in a 432-bed university-based tertiary-care hospital is described. A subcommittee of the hospital's pharmacy and therapeutics committee developed prescribing criteria for antimicrobials thought to have a specific place in the treatment of various infections. The criteria were based primarily on patient needs, but when two therapies were thought to have similar effectiveness and similar toxicity profiles, cost became the deciding factor in drug selection. Educational packets were designed to assist physicians in prescribing criteria-based antimicrobials. An antimicrobial order form was also developed. The program was implemented after an extensive orientation and education period; data on antimicrobial use were collected for the first year of the program. Hospitalwide compliance with the criteria was 89%, although compliance in certain departments was poorer. The database was formulated to be both service- and physician-specific for the purposes of reporting and education.

Comparison of normal saline and heparin solutions for maintenance of arterial catheter patency.

A double-blind, randomized study was conducted in 30 adult medical intensive care unit patients to determine if the presence of heparin in continuous-flush solutions prolongs the functional life span of radial arterial catheters compared with catheters flushed with solutions not containing heparin. Patients were consecutively entered into the study and randomly assigned to receive arterial line flush solutions containing 0.9% sodium chloride (NSS) or heparin 4 U/ml in 0.9% sodium chloride. The flow rate of each flush solution was approximately 3 ml/hr. Use of the heparin-containing flush solution resulted in a catheter survival rate of 86% at 96 hours compared with a rate of only 52% after 40 hours with NSS (p less than 0.05). In addition, the heparin-flushed catheters required significantly less manipulation to prevent catheter occlusion and arterial pressure-wave dampening (p less than 0.01). The use of NSS as a continuous flush for radial artery catheters is associated with an increased frequency of catheter occlusion and malfunctions compared with solution containing heparin, and thus is not recommended in patients with normal coagulation status and platelet count.

The prophylactic use of antimicrobials in surgery.

During the period August 1976 to June 1982, there were 98 reports of antimicrobial prophylaxis in human surgery that were judged unevaluable. Our review, coupled with that of Chodak and Plaut, identified studies of 126 antibiotic regimens that were considered evaluable and a total of 205 studies considered unevaluable. A decrease in infection rate in antibiotic-treated patients compared to non-antibiotic-treated patients was seen in 120 (95%) of the evaluable regimens. Ninety-nine (79%) of these 120 regimens produced statistically significant reductions in the infection rate (P less than .05, chi 2 analysis). The majority of the antibiotic regimens were tested in procedures that were classified as clean-contaminated. Of the regimens that yielded a statistically significant reduction in infection rate with antimicrobial therapy, in 66 (67%) the agents were used for 24 hours or less. Five regimens were identified in which a higher infection rate occurred in specific patient groups when prophylactic antibiotics were used, but the differences were not statistically significant. In the overwhelming majority of evaluable studies, antibiotics decreased the incidence of surgical infection compared with non-antibiotic groups. The available data also support the effectiveness of short prophylactic antibiotic courses of 24 hours' duration or less. The duration necessary for antibiotic prophylaxis was specifically tested in nine regimens. In all nine, a short course (less than 24 hours) of antibiotic prophylaxis was as effective as longer periods of therapy (24 hours to 5 days) in preventing infection.

Evaluation of new cephalosporins for prophylaxis of surgical infection.

The appropriate use of recently marketed cephalosporins for antimicrobial prophylaxis during surgery is discussed. New cephalosporins (cefamandole, cefoxitin, cefotaxime, moxalactam, and cefoperazone) are often substituted in situations where older, "first-generation" cephalosporins or other antimicrobials traditionally have been used. Adoption of these newer agents for routine use in prophylaxis of surgical infection has led to concerns of substantially increased costs as well as development of bacterial resistance. To date, some of the newer cephalosporins have been investigated for prophylaxis of postoperative infection in cesarean section, vaginal hysterectomy, gastrointestinal surgery, open-heart surgery, and total-hip replacement. Assessment of new cephalosporins for surgical prophylaxis should include: (1) the nature of infection with each specific type of procedure, (2) the effect of antimicrobials on prevention of infection with specific procedures, and (3) factors related to the institutional environment. For the surgical procedures listed above, newer cephalosporins either have not been studied or studies have not demonstrated a reduction in postoperative infection rates in comparisons with "first-generation" cephalosporins. Valid prophylactic uses for the newer agents may arise if comparative studies demonstrate postoperative infection rates lower than with regimens using the older cephalosporins or with other established regimens. Currently, none of the newer cephalosporins can be recommended for routine use in the prophylaxis of surgical infection.

Drug delivery for intractable cancer pain. Use of a new disposable parenteral infusion device for continuous outpatient epidural narcotic infusion.

Administration of narcotic analgesics through the epidural route has proven useful for treating pain of acute and chronic nature. This route of narcotic administration is frequently chosen for cancer patients with intractable pain that may be refractory to treatment by conventional oral or parenteral therapy. Implantable constant infusion devices have been commonly described as an alternative drug delivery system for this type of patient. This case report describes the use of the Travenol Infusor (Travenol Laboratories Inc., Deerfield, Illinois) an external, lightweight, disposable, drug delivery device for delivering continuous epidural morphine infusion to a patient with severe cancer pain. The patient has achieved stable pain relief for greater than 8 months without hospital admission for pain control, or management of complications due to the drug delivery system. The Travenol Infusor may prove to be an alternative drug delivery system for patients requiring continuous epidural narcotic infusion.

Hemodialysis clearance of pentobarbital during continuous infusion.

The hemodialysis clearance of pentobarbital during continuous infusion was determined in a 34-year-old man in acute renal failure. Pentobarbital specimens were obtained simultaneously from arterial blood entering and leaving the dialysis machine at five 1-h intervals. The mean hemodialysis clearance of pentobarbital was 22.3 ml/min. Pentobarbital concentration was relatively unaffected throughout the dialysis period, because of the high dose and continuous infusion of a drug with low hepatic intrinsic clearance and a short dialysis period. A large contribution to total body clearance was not evident, and dosage adjustment would have been unwarranted.

Opioid analgesics versus ketorolac in spine and joint procedures: impact on healthcare resources.

BACKGROUND: Ketorolac's efficacy as a postoperative analgesic has been shown to be comparable to that of narcotic analgesics, but with significantly fewer narcotic-related adverse events. OBJECTIVE: To assess whether the choice of postoperative analgesic, narcotic or ketorolac, has an impact on healthcare resource utilization and cost durng inpatients' recovery period. DESIGN: Retrospective, multicenter, controlled, parallel, cost-minimization analysis. SETTING: Six US teaching hospitals. PATIENTS: This study included 559 patients that underwent either a spine or joint procedure and received adequate doses of narcotic (n = 284 of either morphine or meperidine) or ketorolac (n = 275). MEASUREMENTS: Time to reach recovery milestones, average utilization of healthcare resources, and average per-case postoperative treatment cost. RESULTS: Several recovery milestones, including time to first bowel movement, first oral intake, and first unassisted ambulation, were reached sooner in the ketorolac group, with a resultant shorter mean length of postoperative stay (narcotic 3.78 d, ketorolac 2.80 d; p = 0.01). Total per-patient cost of treatment was 32% greater in the narcotic group, resulting primarily from higher costs associated with hospitalization. CONCLUSIONS: Despite the higher acquisition cost of medication, healthcare resource utilization and total per-patient cost of treatment were lower for patients in the ketorolac group compared with patients in the narcotic analgesic study group. The majority of patients in the ketorolac group were also given concurrent narcotic analgesics; therefore, the beneficial effects observed may be secondary to the combination of ketorolac and narcotic analgesics.

Factors potentially influencing aminoglycoside use and expenditure.

Factors that may have influenced aminoglycoside use and expenditure in one hospital were examined. Factors that were evaluated as to their influence on aminoglycoside-use patterns were: (1) formulary status; (2) bacterial susceptibility patterns; (3) identified or perceived differences in toxicity; (4) changes in patient population; (5) price paid by the hospital for aminoglycosides; (6) distribution of newsletters or memoranda; (7) advertising and detailing; and (8) pharmacy policies. For FY 1976-77 to 1979-80, the largest proportion of aminoglycoside expense was for gentamicin. During FY 1980-81, the expenditure for gentamicin decreased and tobramycin accounted for the largest proportion of total expenditure. Monthly gentamicin use decreased 20% during FY 1980-81 from the previous year. Tobramycin use increased from January 1979 to November 1980 and decreased from December 1980 to June 1981. Kanamycin use and amikacin use were fairly constant during the study period. Based on temporal relationships, the following factors appeared to influence aminoglycoside use and expenditure: (1) a study conducted at the institution from June 1977 to June 1979 comparing gentamicin and tobramycin nephrotoxicity; (2) a comparative nephrotoxicity study published in a widely circulated medical journal in May 1980; and (3) an intramural newsletter and memorandum distributed in March 1981 encouraging selective aminoglycoside use. The identification of factors that potentially influenced aminoglycoside use can be used to anticipate the future impact of similar events and to devise strategies to influence antimicrobial use.

Parenteral safflower oil emulsion (Liposyn 10%): safety and effectiveness in treating or preventing essential fatty acid deficiency in surgical patients.

The safety and effectiveness of a 10% safflower oil emulsion in treating or preventing essential fatty acid deficiency was tested in a prospective study of 15 surgical patients requiring total parenteral nutrition for two to four weeks. Three dosage regimens were evaluated including: Group I: 4% of calories as linoleate daily (five patients), Group II: 4% of calories as linoleate every other day (two patients), and Group III: 8% of calories every other day (eight patients). Patients were monitored for laboratory changes from baseline specifically in those areas where previous fat emulsions have caused serious deviations. No significant changes were noted in hematologic parameters, coagulation studies, cholesterol and triglyceride serum levels. Although there were sporadic mild deviations in liver function changes in several patients, no clinically significant adverse effects could be directly attributed to infusion of the fat emulsion. Three patients had baseline triene/tetraene ratios of 0.4 or greater, indicative of essential fatty/acid deficiency, and these ratios dropped to less than 0.4 within eight days of beginning therapy with the parenteral fat emulsion. The remaining 12 patients maintained a normal triene/tetraene ratio of less than 0.4 throughout the 28 day study period. All three dosage regimens were considered effective for treatment and prevention of essential fatty acid deficiency.

Antimicrobial prophylaxis in surgery: Part 1.

The use of antimicrobial agents for prophylaxis in gastrointestinal, obstetric-gynecologic, cardiovascular-thoracic, orthopedic, and head-and-neck surgery is reviewed. English-language reports of studies on antimicrobial prophylaxis in surgery are reviewed. The methodology of each study was evaluated using predetermined criteria, and "evaluable" regimens are included in this review. For each type of surgical procedure, the discussion covers normal infection rates, probable bacterial contaminants, evaluable studies, and specific treatment recommendations. Regimens found to be evaluable numbered 76, with 72 of these showing a decreased infection rate with antibiotics versus placebo. Statistically significant decreases were found in 57 regimens. When properly used, antimicrobial agents have experimental justification for use in some surgical procedures. Factors that should be considered in the risk-benefit equation include: potential for and significance of surgical infection; cost, adverse effects, and ease of administration of antimicrobial agents; development of resistant microorganisms and of superinfection; and improper reliance on antimicrobial agents with resulting disregard for aseptic technique.

Oral phenytoin loading in adults: rapid achievement of therapeutic plasma levels.

Oral loading doses of phenytoin were estimated from a simplified pharmacokinetic model. Twenty patients were administered a calculated average dose of 19.1 mg per kilogram of phenytoin divided into two to four increments given over 3 to 21 hours (10.55 +/- 4.74, mean +/- SD). Plasma samples drawn 2 to 22 hours (10.75 +/- 4.32, mean +/- SD) after completion of the loading dose resulted in therapeutic levels ranging from 8.1 to 18.0 microgram per milliliter (11.42-11.37 +/- 2.41, mean +/- SD). Thus, this regimen in which no increment of the loading dose exceeds 600 mg is sufficient to achieve and maintain therapeutic plasma concentrations 18 to 24 hours after initiation of the loading dose.

Postinfusion phlebitis associated with a syringe system versus minibags.

The incidence of postinfusion phlebitis was compared in patients receiving i.v. drugs in 50- and 100-mL minibags of 5% dextrose injection or 0.9% sodium chloride injection versus 20- and 50-mL quantities of sterile water for injection or 0.45% sodium chloride injection in plastic syringes used with a venting administration set. Patients 16-75 years of age receiving one or more i.v. drugs and a concurrent maintenance i.v. fluid through a Teflon catheter in a peripheral vein were included. Patients receiving antineoplastic drugs, drugs that require a minimum diluent volume greater than 50 mL, or i.v. heparin sodium in doses of greater than or equal to 500 units/hr were excluded. For the syringe system, the type and amount of diluent were selected to achieve a solution osmolarity of approximately 300 mOsm/L. Patients' i.v. sites were examined every eight hours for 72 hours, and phlebitis was assessed according to predetermined criteria. There were 47 patients in the minibag group and 46 in the syringe group. There were no significant differences between the groups in demographic characteristics, catheter size, duration of infusion, number of doses, number or type of i.v. drugs, or incidence or severity of phlebitis. Administration of i.v. drugs with controlled solution osmolarity via this syringe infusion system was not associated with an incidence of postinfusion phlebitis different from that for i.v. drugs diluted in minibags.

The effect of ten and twenty per cent safflower oil emulsion given as thirty to fifty per cent of total calories.

In a prospective study of seven patients undergoing operations, 10 and 20 per cent safflower oil emulsions were found to be safe and effective as a major component of adult parenteral nutrition. Specifically, clinically important adverse effects of the emulsions as monitored by clinical evaluation and screening hematologic and blood chemistry determinations were not identified. Further, an extensive coagulation profile in these patients has failed to identify procoagulant effects of parenteral safflower oil. The optimum dosage of fat for a balanced parenteral diet is not known. Linoleic acid administered as 4 per cent of total calories every other day will treat or prevent essential fatty acid deficiency, and this dosage may be considered a minimum requirement for parenteral fat. The data from this study demonstrate parenteral safflower oil administered as 30 to 50 per cent of total calories is effective in achieving nitrogen balance. The implication is that fat emulsions today allow the use of parenteral diets that match the normal diet consumed orally in terms of the balance of protein, carbohydrate and fat.

Vancomycin pharmacokinetics in normal and morbidly obese subjects.

In an uncontrolled study, vancomycin pharmacokinetics were determined in four normal (total body weight [TBW], 65.9 to 89.1 kg) and six morbidly obese (TBW, 111.4 to 226.4 kg) subjects. The morbidly obese subjects were investigated 3 to 4 h after gastric bypass surgery. Mean terminal half-lives, volumes of distribution, and total body clearances for the normal controls and the morbidly obese (TBW, 111.4 to 226.4 kg) subjects. The morbidly obese subjects were investigated 3 to 4 h after gastric bypass surgery. Mean terminal half-lives, volumes of distribution, and total body clearances for the normal controls and the morbidly obese subjects were 4.8 h, 0.39 liter/kg, and 1.085 ml/min per kg versus 3.2 h, 0.26 liter/kg TBW, and 1.112 ml/min per kg TBW. The mean terminal half-life and volume of distribution values were significantly different between the two groups. Strong correlations were found between TBW and both volume of distribution (correlation coefficient, 0.943) and total body clearance (correlation coefficient, 0.981). There results implied that TBW should be used to calculate vancomycin doses for morbidly obese patients. This was supported by the finding that there was no significant difference in the daily dose (in milligrams per kilogram per day) required to produce an average steady-state concentration of 15 micrograms/ml in the two groups (23.4 +/- 1.5 mg/kg per day for normal weight subjects and 24.0 +/- 3.4 mg/kg per day TBW for the postsurgery morbidly obese subjects). Therefore, the morbidly obese required higher total doses (in milligrams per day) than did normal weight subjects to achieve the same mean steady-state concentrations. In addition, normal weight and morbidly obese subjects had similar volumes of the central compartment (7.7 and 6.4 liters, respectively). To avoid high transient peak concentrations which would occur when obese patients are given larger total doses (in milligrams per day), maintenance doses may be given at more frequent intervals. The shorter mean terminal half-lives observed in morbidly obese patients allows more frequent dosing without excessive accumulation.

Theophylline hemodialysis clearance.

The hemodialysis clearance, total body clearance off dialysis, and protein binding for theophylline were determined in a 64-year-old cigarette-smoking male in acute renal failure. The hemodialysis clearance of 39.4 ml/kg/hr was comparable to two other reports and indicated that theophylline was significantly hemodialyzed. The total body clearance of 52.4 ml/kg/hr was similar to that observed in non-renal-failure smoking patients and suggested that renal failure did not appreciably affect the total body clearance in the patient. The plasma protein binding was 40% before dialysis and 33% after dialysis. This finding implied that renal failure and hemodialysis may alter protein binding compared to that in normal adults. Theophylline plasma levels should be monitored in renal failure patients because the drug is hemodialyzed. Decreased plasma protein binding may indicate the need for a lower therapeutic range in this patient population.