Journal of Pharmacy Technology

To review the literature concerning the use of nebulized opioids to treat dyspnea in terminally ill cancer patients.

English-language journal articles were obtained by a MEDLINE search (1966-August 1997).

All clinical trials and case reports involving nebulized opioids. Representative studies discussing neurogenic inflammation and pulmonary opioid receptors were also reviewed.

Studies were selected for review on the basis of study design and use of nebulized opioids. Case reports were selected from the palliative care literature.

High-density, low-affinity opioid receptors have been identified in lung tissue and may play a role in the alleviation of dyspnea in some patients. The activation of these receptors in the lung may attenuate the release of inflammatory mediators and neuropeptides such as substance P. However, because nebulized opioids are absorbed buccally or through the airway mucosa, the relief observed may be due to a central rather than peripheral effect.

Several case reports in the palliative care literature have described favorable results when nebulized opioids are used to treat dyspnea. However, data from controlled trials in populations other than patients with cancer do not substantiate the use of nebulized opioids. Unfortunately, controlled clinical trials have not been conducted in cancer patients; thus, extrapolation is difficult. Well-designed clinical trials in patients with cancer are necessary to determine the efficacy of nebulized morphine in treating dyspnea.

To describe a case of necrotizing fasciitis (NF) that occurred following minor clean surgery in a seemingly otherwise healthy man who was taking over-the-counter (OTC) ibuprofen 200 mg and aspirin 325 mg before surgery.

A 71-year-old white man underwent an uncomplicated laparoscopic cholecystectomy. His only medical disorder prior to surgery was osteoarthritis, for which he took OTC-strength ibuprofen; his only other regular medication was one aspirin 325-mg tablet daily for prevention of cardiac disease. Within 48 hours of the surgery, the onset of NF was apparent, and extensive tissue excision and debridement was required 1 week after the operation. All nonsteroidal antiinflammatory drugs (NSAIDs) were withheld. The patient survived a complicated clinical course over the next month.

A review of proposed risk factors for the development of NF in the patient indicated surgery and NSAID use. Analysis of the probability of NSAID use as a causative factor for the adverse reaction of NF suggests a possible role. This case suggests that NSAID use in lower OTC dosages may contribute to the onset or course of NF. The case report adds to existing literature suggesting an association between NSAID use and the development or course of NF.

NSAIDs are widely used drugs, and any association as a causative or provocative factor for NF is a rare finding. However, practitioners should be aware of the proposed association.

To compare the safety and efficacy of cefoperazone plus sulbactam (CPZ + SB) (3 g [2:1] every 8 h) and ceftazidime (CTZ) (2 g every 8 h) as monotherapy in the empiric treatment of febrile neutropenia in patients with cancer.

One hundred eighteen cancer patients with chemotherapy-associated neutropenia and fever. Most patients (82) received norfloxacin and fluconazole as prophylaxis.

Fifty-nine patients were enrolled in the CPZ + SB group, and 59 were enrolled in the CTZ group. The mean duration of antibiotic therapy was less than 10 days in both groups. Forty-three patients (19 in the CPZ + SB group and 24 in the CTZ group) were bacteremic, and 7 others had cellulitis. Of the 56 microorganisms producing bacteremia, 51 were gram-positive bacteria, mostly staphylococci (28 isolates) and streptococci (22 isolates). Gram-positive cocci were more frequently resistant to CTZ than to CPZ + SB (77% vs. 40%, respectively; p < 0.002). However, the clinical response rate at 72 hours of therapy was 53% in the CPZ + SB group and 52% in the CTZ group (p = 1.0). At the end of therapy, clinical responses were similar in the two groups (p = 0.19). Clinical success with antibiotic modification was seen in 42% of the CPZ + SB recipients and in 58% of CTZ recipients (p = 0.10). Bacteriologic eradication among bacteremic patients appeared to be slightly better in the CPZ + SB group (79% vs. 54%; p = 0.09). Except for rashes in 3 patients (1 in the CPZ + SB group and 2 in the CTZ group), both drugs were well tolerated. Adverse events included superinfections, transient elevation of serum transaminase concentrations, diarrhea, and chills.

CPZ + SB was superior to CTZ in its in vitro activity against aerobic gram-positive cocci encountered in the study; however, the clinical efficacy and safety of the two drug treatments were similar in the empiric therapy for febrile neutropenia.

To report a case of trazodone-associated syncope in a 19-year-old woman with congenital cardiac anomalies and to review risk factors and mechanisms involved in this case.

A 19-year-old woman diagnosed with Noonan syndrome with congenital cardiac anomalies tolerated sertraline, but had a syncopal episode when trazodone was used. There was no recurrence of syncope after the trazodone was discontinued.

The syncopal episode could have resulted from either trazodone or congenital heart disease, but it most likely resulted from a trazodone–congenital heart disease interaction. Trazodone is not cardiotoxic in most patients; our patient was probably vulnerable to the cardiotoxic effects of trazodone due to congenital cardiac defects.

Trazodone can precipitate arrhythmias or syncope in susceptible patients with heart disease and should be prescribed cautiously in patients with congenital heart disease. In such cases, it may be safer to use a selective serotonin-reuptake inhibitor.