Annals of Pharmacotherapy

Dick, Michael; Dasta, Joseph F.; Choban, Patricia S.; Sinha, Renu; Flancbaum, Louis

doi: 10.1177/106002809402800701pmid: 7949495

OBJECTIVE:To determine whether the diuretic and natriuretic effects of low-dose dopamine (2.5 μ/kg/min) are associated with changes in serum aldosterone concentration.DESIGN:Prospective clinical study.SETTING:Surgical intensive care unit (SICU) of a university hospital.PARTICIPANTS:Oliguric (urine output <0.5 mL/kg/h) SICU patients. All patients were resuscitated to pulmonary artery occlusion pressure > 10 mm Hg, mean arterial pressure >65 mm Hg, and cardiac index >2.5 L/min/m2. Patients with a serum creatinine concentration > 176.8 μmol/L (2.0 mg/dL.), those who received diuretics within 12 hours prior to entry into the study, and renal transplant recipients were excluded.MAIN OUTCOME MEASURES:Hourly urine output (mean ± SD) was recorded 2 hours before and for 6 hours after the initiation of lowdose dopamine. Urine sodium and serum aldosterone concentrations were obtained prior to and 6 hours after the start of low-dose dopamine.RESULTS:Fifteen patients were enrolled in the study. Urine output (mean ±SD) increased from 0.31 ± 0.11 mL/kg/h before to 0.80 ± 0.34 mL/kg/h following low-dose dopamine (p<0.01). Urine sodium concentrations increased from 46 ± 32 mmol/L baseline to 72 ± 53 mmol/L following low-dose dopamine (p<0.05), and serum aldosterone concentrations decreased from 415.82 ± 341.48 pmol/L prior to low-dose dopamine infusion to 256.04 ± 204.17 pmol/L (p<0.05). Cardiac output, pulmonary artery occlusion pressure, mean arterial pressure, and heart rate did not change.CONCLUSIONS:Low-dose dopamine significantly increases urine output and urine sodium excretion in oliguric, critically ill, surgical patients, and is associated with a decrease in serum aldosterone concentration. The diuretic and natriuretic effects of low-dose dopamine may be, in part, related to a dopamine-mediated inhibition of aldosterone secretion.

Jones, Lori A.; Gonzalez, Edgar R.; Reines, H. David; Venitz, Jurgen

doi: 10.1177/106002809402800702pmid: 7949496

OBJECTIVE:To compare the effects of intermittent bolus versus continuous infusion intravenous famotidine on gastric pH in critically ill trauma patients.DESIGN:Twenty patients were randomized to receive famotidine by intermittent bolus or continuous infusion for 24 hours. Patients fasted during the study period. Hourly gastric pH measurements were made using an indwelling sensor/sump tube.SETIING:The study was conducted in a university teaching hospital.PARTICIPANTS:Adult patients admitted to the neurosurgical or surgical/trauma intensive care unit within 72 hours of traumatic injury were enrolled in the study if they had two consecutive hourly gastric pH readings of <4 without receiving antacids, sucralfate, or histamine2-antagonists.MAIN OUTCOME MEASURES:Groups were compared with regard to (1) total dose of famotidine received/24 hours, and (2) number of dosage changes required to maintain a gastric pH value of ≥4.RESULTS:The median dose of famotidine required to maintain a gastric pH ≥4 was 50 mg/24 h (25th–75th percentiles = 40–55 mg) in the intermittent bolus group compared with 42 mg/24 h (25th–75th percentiles = 42–52 mg) in the continuous infusion group (p=0.9577). A dosage increase was required by 5 of 8 patients (62 percent) receiving intermittent bolus therapy, whereas only 2 of 8 patients (25 percent) in the continuous infusion group required a dosage adjustment (p=0.315, power=0.318).CONCLUSIONS:Intravenous famotidine (40–50 mg/d) effectively controlled gastric pH in critically ill trauma patients. Patients treated with intermittent bolus therapy required slightly more drug and more frequent dosage adjustments to achieve a gastric pH ≥4. These differences did not reach statistical significance.

Laursen, Torben; Ovesen, Per; Grandjean, Birgitte; Jensen, Sigrid; Jørgensen, Jens Otto L.; Illum, Peter; Christiansen, Jens Sandahl

doi: 10.1177/106002809402800703pmid: 7949497

OBJECTIVE:Current growth hormone (GH) therapy with daily subcutaneous injections results in elevated serum concentrations of GH lasting for several hours, whereas physiologic GH secretion is characterized by a short-duration peak and low basal concentrations. A closer imitation of this pattern might be achieved by administering GH nasally. We studied the effect on the absorption of nasally administered human GH of increasing concentrations of the enhancer didecanoyl-L-α-phosphatidylcholine (DDPC).DESIGN:Four formulations of nasal GH containing the enhancer DDPC in the relative concentrations 0, 4,8, and 16% w/w were administered in random order.SETTING:Participants were admitted to the hospital during the four study periods.INTERVENTIONS:On four occasions the subjects received GH 6 IU (2 mg) in each nostril. Blood was sampled frequently for four hours. Anterior rhinoscopy was performed at 0 and 4 h. During the study the subjects completed a questionnaire to record nasal symptoms.PATIENTS:Sixteen healthy subjects were examined at 0800 h after an overnight fast.MAIN OUTCOME MEASURES:Bioavailability of a nasal preparation of human GH: area under the curve (AUC), the maximum concentration(Cmax), and the time to reach maximum concentration (tmax). Scores for each nasal symptom were recorded as were the total scores.RESULTS:AUC, Cmax, and tmax,. were not significantly affected by increasing the DDPC concentration from 0 to 4 percent or from 8 to 16 percent. AUC and Cmax, however, increased significantly when the concentration of DDPC was changed from 4 to 8 percent. Mean (±SD) AUC (μg·h/L) increased from 20.51 ± 10.53(4 percent)to 46.14 ± 34.59 (8 percent), (p<0.005). Mean (±SD) of Cmax (μg.L) increased from 11.11 ± 5.02 (4 percent) to 28.22 ± 20.85 (8 percent), (p=0.OO2). Mean (±SD) of tmax (min) was not significantly different on the four occasions(range 40.6 ± 36.4 to 61.0 ± 45.2 min, p=0.13). The symptom scores (range 17.56–21.5, maximum 360) were not significantly different (p=0.59).CONCLUSIONS:Increasing the relative concentration of the enhancer DDPC increases the absorption of nasally administered GH.

Eisele, George; Gilmore, Linda L.; Blanchard, Edward B.

doi: 10.1177/106002809402800704pmid: 7949498

OBJECTIVE:To determine whether beta-blocker withdrawal under close medical supervision poses undue risks.DESIGN:Retrospective case review. Data extracted from previous study.SUBJECTS:114 hypertensive subjects tapered from beta-blocker therapy. Subjects were a subset of patients originally studied for blood pressure medication withdrawal and biofeedback training.MAIN OUTCOME MEASURES:Frequency of symptoms and adverse effects reported by subjects during medication taper to the study nurse.RESULTS:Symptoms were no more likely to occur with beta-blocker withdrawal than with withdrawal of other types of antihypertensive medications. Most adverse effects were classified as minor. Two subjects experienced major symptoms. One subject required reinstitution of beta-blockers for palpitations, and another exhibited angina upon beta-blocker withdrawal.CONCLUSIONS:In well-screened patients under careful monitoring, withdrawal from beta-blockers appears to present a small, manageable risk.

Rayani, Shelina A.; Nimmo, Cindy J. Reesor; Frighetto, Luciana; Martinusen, Shelagh M.; Nickoloff, Donna M.; Reece, Donna E.; Jewesson, Peter J.

doi: 10.1177/106002809402800705pmid: 7949499

OBJECTIVE:To assess the impact of a standardized acyclovir prophylaxis protocol for the prevention of herpes simplex virus (HSV) infection and disease in bone marrow transplant and leukemic patients.DESIGN:Two-phase, open sequential study involving prospective patient monitoring and retrospective health record review.SETIING:Tertiary care teaching hospital.PATIENTS:Fifty-seven patients (35 preprotocol, 22 postprotocol) who received acyclovir for HSV prophylaxis during an 18-month study period.INTERVENTIONS:An acyclovir HSV prophylaxis protocol was developed and implemented. Under this protocol, all HSV immunoglobulin G-seropositive hematology patients received an acyclovir regimen of 125 mg/m2 iv q6h or 600 mg po q6h (if tolerated) from day −5 to day 30. Regimens not matching protocol were modified by pharmacists in conjunction with the prescriber. All treatment courses were followed daily by pharmacists to modify dosage according to renal function and assess appropriateness of the iv route. Tablets, capsules, or suspensions were promoted if the patient was considered tolerant of the oral route.MAIN OUTCOME PARAMETERS:Outcome parameters included (1) incidence of parenteral, oral, or combined therapy; (2) total prophylactic acyclovir dose per patient; (3) mean prophylactic acyclovir daily dose; (4) mean duration of acyclovir prophylaxis; and (5) HSV reactivation rate.RESULTS:Following implementation of the protocol, the mean total iv acyclovir dose per patient decreased from 20.1 g (range 3.6–109.5) to 11.7g (range 1.0–43.0; p=0.1162). The mean cumulative oral dose increased from 12.1 g (range 0.4–70.0) to 33.1g (range 2.4–93.6; p=0.00(7). Mean duration of therapy increased from 27.6 to 33.5 days (p=0.23). The mean duration of oral therapy increased from 10.5 days (±SD 10.9) to 17.2 days (±SD 12.1) (p=0.034). The appropriateness of use of the iv dosage form increased from 53 to 88 percent of treatment days (p=0.013). No difference in HSV reactivation rate was observed when comparing patients prior to and following protocol implementation. A drug acquisition savings of $1112.00 (CON) per patient was realized.CONCLUSIONS:The implementation of a standardized HSV acyclovir prophylaxis protocol has resulted in significant drug acquisition cost savings without an apparent negative impact on patient outcome.

Krick, Stacie E.; Lindley, Celeste M.; Bennett, Michelle

doi: 10.1177/106002809402800706pmid: 7949500

OBJECTIVE:To assess pharmacists' knowledge, attitudes, and beliefs regarding the use of narcotics in cancer pain management, identify pharmacist counseling activities for cancer pain patients, assess pharmacy-related barriers to cancer pain management, and evaluate the availability of narcotic analgesics.METHODS:Mailing of a six-page survey.SETTING:Five hundred randomly selected pharmacists registered in North Carolina.PARTICIPANTS:Of 500 pharmacists surveyed, 141 surveys were completed and returned for a response rate of 28.2 percent.RESULTS:Pharmacists surveyed were knowledgeable regarding the problem of undertreatment of cancer pain. More than 80 percent of respondents replied that most cancer patients experience pain at some time during their illness. Eighty-five percent of respondents agreed that the nurse must believe the patient's report of pain and that the patient is the best judge of the intensity of the pain. Conservative physician prescribing patterns and conservative administration patterns of nurses were identified as perceived barriers to adequate pain management by 51 and 44 percent of respondents, respectively. Less than 30 percent of respondents frequently counseled cancer pain patients and were unable to identify patients who have cancer pain as a major medical illness. Hospital pharmacists recommended adjunctive therapy more often than did community pharmacists (p=0.013). Interventions in pain management regimens were more often conducted by hospital pharmacists than by community pharmacists (p=0.049). Differences in availability of narcotics was noted among practice sites for some more potent narcotics. Of the pharmacists surveyed, only 43 percent had attended a continuing education program on cancer pain management. Ninety-six percent of respondents were interested in attending a continuing education program in the future.CONCLUSIONS:Pharmacists in North Carolina are aware that the undertreatment of cancer pain is a serious medical problem. Unfortunately, pharmacists appear to be unable to identify patients with cancer pain as a major medical problem; therefore, counseling activity is limited. Addiction is still perceived as a barrier by some pharmacists. Through organizations such as the North Carolina Pain Initiative, these problems can be addressed.

Goss, Thomas F.; Forrest, Alan; Nix, David E.; Ballow, Charles H.; Birmingham, Mary C.; Cumbo, Thomas J.; Schentag, Jerome J.

doi: 10.1177/106002809402800707pmid: 7949501

OBJECTIVE:To compare two antibiotics at equal ranges of area under the inhibitory curve (AUIC) exposure to determine if the rate of bacterial eradication differed between these antibiotics.DESIGN:Retrospective comparison of two previously collected studies of similar patients with nosocomial pneumonia.SETTING:Hospitalized patients, most intubated in critical care units with nosocomial pneumonia.PARTICIPANTS:Patients treated with either iv ciprofloxacin (n=74) or the iv third-generation cephalosporin cefmenoxime (n=43) were compared for their length of treatment required to eradicate bacterial pathogens from their respective infection sites, using serial cultures from the site of infection. All patients were also assessed for clinical outcomes. Serum samples were obtained to evaluate individual patient antibiotic pharmacokinetics, which were used to model pharmacodynamics of response. The HPLC assay used for each antibiotic had interday coefficients of variation <10 percent. Serum concentration versus time profiles were fit using the computer program ADAPT II to determine pharmacokinetic parameters for each patient. The primary drug exposure measure that related to response was the AUIC, calculated as steady-state AUC0–24/minimum inhibitory concentration.RESULTS:AUIC values in the patients ranged from 6.0 to more than 7000, yet the AUIC value was highly predictive of time to bacterial eradication (p<0.OO 1). Although more than 75 percent of patients eventually achieved eradication of pathogens from tracheal aspirate cultures, ciprofloxacin and cefmenoxime differed significantly in the time required to sterilize these cultures. At appropriate AUIC values (>250) for ciprofloxacin, the median time to eradication was two days, while cefmenoxime (also at AUIC values >250) required six days to achieve the same result.CONCLUSIONS:We conclude that the more rapid in vitro bacterial killing, which is characteristic of ciprofloxacin at optimal AUIC values, can manifest in vivo as more rapid clearance of bacteria from the respiratory tract of patients, even when both agents are controlled for initial antibacterial exposure (i.e., same AUIC).

Fan-Havard, Patty; Sanchorawala, Vaishali; Oh, Julee; Moser, Eileen M.; Smith, Stephen P.

doi: 10.1177/106002809402800708pmid: 7949502

OBJECTIVE:To report a possible interaction between foscarnet and ciprofloxacin in two patients with AIDS, cytomegalovirus (CMV) retinitis, and disseminated Mycobacterium avium complex (MAC) infection and to review the available literature related to foscarnet associated seizures.DATA SOURCE:Case report information was obtained from Medical Service Daily Rounds during the patients' hospitalization and from the patients' medical records. Computerized (MEDLINE) and manual (Index Medicus) search methods were used to obtain English-language literature published between 1980 and 1993.DATA SYNTHESIS:Foscarnet is a synthetic antiviral agent with activity against herpes viruses and HIV. The incidence of seizures with foscarnet infusion is high, ranging from 13 to 15 percent. Predisposing factors such as renal impairment, electrolyte and metabolic abnormalities, and underlying neurologic disorders have been associated with seizures during foscarnet therapy. We describe two patients with AIDS who developed generalized tonic-clonic seizures while receiving foscarnet and ciprofloxacin for the treatment of CMV retinitis and disseminated MAC infection, respectively. Neither of the patients had any of the aforementioned risk factors for foscarnet-associated seizures.CONCLUSIONS:Concurrent administration of ciprofloxacin, a known epileptogenic agent, and foscarnet may predispose patients to the development of seizures.

Dorevitch, Abraham; Davis, Hillel

doi: 10.1177/106002809402800709pmid: 7949503

OBJECTIVE:To report two cases of sexual dysfunction induced by fluvoxamine, a selective serotonin reuptake inhibitor (SSRI).SETTING:University teaching hospital.PATIENTS:Two depressed patients who developed ejaculation and orgasmic difficulties after initiation of fluvoxamine therapy.DISCUSSION:The literature concerning sexual dysfunction with serotonergic antidepressants is reviewed, and speculated mechanisms for this untoward effect are discussed.CONCLUSIONS:Sexual dysfunction associated with antidepressant drugs, including SSRIs, may be underreported. This troublesome adverse effect may significantly affect patient comfort and compliance. Careful evaluation of sexual function is warranted, prior to and during drug treatment, especially as more serotonergic antidepressant agents become available.

Chapron, Dennis J.; Korman, Lisa B.; Barry, William L.

doi: 10.1177/106002809402800710pmid: 7949504

OBJECTIVE:To describe a patient with gastric retention of enteric-coated magnesium chloride tablets. Potential drug and disease etiologies accounting for failure to empty this dosage form are discussed.DESIGN:Single case report.CASE SUMMARY:A seriously ill patient with metastatic small-cell lung cancer accumulated 21 enteric-coated magnesium chloride tablets in his stomach during a four-day administration period. The patient had gastroscopic evidence of mild pylorospasm and suspected gastric motor dysfunction. The latter may have been the result of several factors including concurrent use of oxycodone, vagal dysfunction from chronic alcoholism and cisplatin-based chemotherapy, and possibly a paraneoplastic neuromuscular syndrome involving the gastrointestinal tract.CONCLUSIONS:Enteric-coated tablets are indigestible solids, often of considerable size. Strong antral contractions, associated with phase 3 of the interdigestive migrating myoelectric complex, are usually required to carry such dosage forms through a normal pyloric channel and into the duodenum. Seriously ill patients who may have gastric hypomotility or pyloric channel narrowing are probably not good candidates for therapy with large enteric-coated dosage forms.