Letters
pentamidine parenterally for seven or more consecutive days as inpatients. After the initial findings of inadequate monitoring based on literature evaluation, guidelines for the optimal method and frequency of evaluating therapy were developed by the antibiotic subcommittee of the pharmacy and therapeutics committee. The following recommendations were made for appropriate monitoring of therapy: (I) daily blood glucose measurements (via serum/finger prick) should be taken-': (2) serum creatinine and aspartate aminotransferase should be measured,':' and complete blood count and electrocardiogram' should be performed prior to starting treatment; and (3) serum creatinine, aspartate aminotransferase, and complete blood counts should be measured twice a week and an electrocardiogram should be taken once a week while receiving therapy. These guidelines were inserted in the pocket formulary and distributed to all housestaff, residents, and medical student interns in June 1990. A follow-up retrospective chart evaluation of patients receiving pentamidine between June I and October 23, 1990, was conducted to assess the impact of this educational intervention. Additional education of clinicians was carried out through circulation of the recommended guidelines via the October issue of the hospital's Pharmacy Bulletin. A third retrospective evaluation of treatment courses (October 24, 1990, to April 15, 1991) assessed the impact of the bulletin distribution. The results of the evaluation are summarized in Table I. Few changes in pentamidine monitoring were evident during the periods prior to developing monitoring guidelines, following formulary circulation, and after bulletin distribution. Only the frequency of monitoring for electrocardiac toxicities through electrocardiogram evaluation increased. The theoretical basis and practical aspects of influencing prescribing have been reviewed." In general, administrative techniques, such as prescribing restrictions, mandatory consultations, or medical management protocols, positively affect prescribing patterns. However, these positive effects may be lost when the administrative program is discontinued. Educational programs ranging from printed, verbal, group, or individualized techniques have been assessed.' One study found that printed information alone does not influence subsequent prescribing." Our results support this finding. Our methodology did not investigate the prescribing practices of individual physicians, but rather the entire medical staff. Because our educational programs were aimed at the entire staff, educational benefit should have been obtained with all prescribers. We did not verify that all prescribers had received and reviewed the educational material. Feedback to individual prescribers has been shown to be beneficial in changing prescribing patterns; although sustained benefit is questionable. We did not provide any prescriber with direct information regarding his monitoring practices. Such methods would be required to optimize the monitoring of pentamidine and correct the deficiencies identified in our audits. A. MELANIE MARTINS, B.Sc.(pharrn.)
Staff Pharmacist (at time of writing) St. Paul's Hospital Vancouver. British Columhia Doctor ofPharmacy Student College ofPharmacy Ohio State University Columbus. Ohio 43210
5. Hershey C, Goldberg H, Cohen D. The effectof computerized feedback coupled with a newsletter upon outpatient prescribing charges. Med Care 1988;26:88-93.
Imipenem lcilastatin-associated hiccups TO THE EDITOR: Seizures are the most frequently observed neurologic adverse reactions following imipenem administration.'? We report a patient with no central nervous system disorders in whom persistent hiccups developed during imipenem/cilastatin (IIC) treatment. A 46-year-old mansustained an openfracture of his lefttibiainJanuary 1991 witha mowing machine. He wasadmitted to the orthopedic unitof University Hospital where he underwent several debriding procedures followed byexternal reduction of the tibia. Over the next few months, purulent drainage from the wound wasnotedthat persisted despite a specific antibiotic regimen. InOctober 1991. an X-ray showed osteomyelitis of thetibia with a sequestrum. Intheoperatingroom on November 18.the necrotic bonewascuretted andthewound packed open. Based on the results of a previous cultureandantibiogram that yielded a growth of multiple pathogens (Staphylococcus aureus,Enterococcus faecalis, two strains of Enterobacteraerogenes, and Aeromonashydrophilai, VC 1g iv infused over60 minutes q6handgentamicin 120mg iv infused over30 minutes q8hwere started. During infusion of the fourth doseof I/C.thepatient experienced nausea, vomiting. andpersistent hiccups. which continued during hissleep. Aftereachof thenextfourdoses. thehiccups worsened. On day3. thepatient awoke early and severe hiccups reappeared promptly afterthefirst morning dose, followed 30 minuteslaterbyvomiting of "coffee-ground" likematerial. Laboratory tests showed a decrease in hemoglobin from 100to 90 gIL. Serumcreatinine, urea,and electrolytes were within the normal range. Anendoscopic procedure wasperformed, which disclosed noabnormalities intheupper gastrointestinal tract. Ranitidine and metoclopramide were administered. The hiccups responded to a decrease in the VC dose to500mganddidnotrecur. The patient had no history of hiccups, abnormal renal function, or underlying central nervous system disease. We believe that a probable link can be established between this case and the use of lie at maximal doses, applying Karch and Lasagna criteria.' To our knowledge this adverse reaction has not been previously reported. No cause is apparent, although one possible explanation may be the loss of inhibition of higher neural centers' upon the hiccup-reflex arc caused by I/C's effects on the gamma-aminobutyric acid receptors in the brain," MARIBEL LUCENA, M.D. Professor ofPharmacology Department ofClinical Pharmacology University Hospital School ofMedicine 29080 Malaga Spain
RAUL ANDRADE, M.D. Professor ofMedicine Department ofGastroenterology
MARIA CABELLO, M.D. Fellow in Clinical Pharmacology Department ofClinical Pharmacology
ENCARNACION CLAVIJO. M.D. Professor of Microbiology Department ofMicrobiology
ENRIQUE QUEIPO DE LLANO, M.D. Head
Department ofOrthopaedic Surgery GLEN R. BROWN, Pharrn.D.
Assistant Director. Clinical Services St. Paul's Hospital
REFERENCES I. Drake S, Lampasona V, Nicks HL, Schwarzmann SW. Pentamidine isethionate in the treatment of Pneumocystis carinii pneumonia. Clin Pharm 1985;4:507-16.
2. Salamone FR, Cunha BA. Update on pentamidine for the treatmentof Pneumocystis carinii pneumonia. Clin Pharm 1988;7:501-10. 3. Raisch DW. A model of methodsfor influencing prescribing: part I. A reviewof prescribing models,persuasion theories, and administrative and educational methods. DICP Ann Pharmacother 1990;24:417-21. 4. Raisch DW. A model of methods for influencingprescribing: part II. A reviewof educational methods. theories of human inference, and delineationof the model. DICP Ann Pharmacother 1990;24:537-42.
REFERENCES I. Barza M. Imipenem: first of a new class of beta-lactarn antibiotics. Ann Intern Med 1985; 103:552-60. 2. Clissoid SP, Todd PA, Campoli-Richards DM. Imipenern/cilastatin. A reviewof its antibacterial activity, pharrnacokinetic properties and therapeuticefficacy. Drugs 1987;33:183-241. 3. Eng RHK, Munsif AN, Yangco BG, Smith SM, Chmel H. Seizure propensity with imipenem. Arch Intern Med 1989; 149:1881-3. 4. Karch FE, Lasagna L. Adversedrug reactions: a critical review.lAMA 1975;234: 1236-41. 5. Newsom-Davis J. An experimental study of hiccup. Brain 1970;93:85172. 6. Kamei C, Sunami A, Tasaka K. Epileptogenic activity of cephalosporins in rats and their structure-activity relationship. Epilepsia 1983; 24:431-9.
The Annals ofPharmacotherapy
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1992 November, Volume 26 •
1459
pentamidine parenterally for seven or more consecutive days as inpatients. After the initial findings of inadequate monitoring based on literature evaluation, guidelines for the optimal method and frequency of evaluating therapy were developed by the antibiotic subcommittee of the pharmacy and therapeutics committee. The following recommendations were made for appropriate monitoring of therapy: (I) daily blood glucose measurements (via serum/finger prick) should be taken-': (2) serum creatinine and aspartate aminotransferase should be measured,':' and complete blood count and electrocardiogram' should be performed prior to starting treatment; and (3) serum creatinine, aspartate aminotransferase, and complete blood counts should be measured twice a week and an electrocardiogram should be taken once a week while receiving therapy. These guidelines were inserted in the pocket formulary and distributed to all housestaff, residents, and medical student interns in June 1990. A follow-up retrospective chart evaluation of patients receiving pentamidine between June I and October 23, 1990, was conducted to assess the impact of this educational intervention. Additional education of clinicians was carried out through circulation of the recommended guidelines via the October issue of the hospital's Pharmacy Bulletin. A third retrospective evaluation of treatment courses (October 24, 1990, to April 15, 1991) assessed the impact of the bulletin distribution. The results of the evaluation are summarized in Table I. Few changes in pentamidine monitoring were evident during the periods prior to developing monitoring guidelines, following formulary circulation, and after bulletin distribution. Only the frequency of monitoring for electrocardiac toxicities through electrocardiogram evaluation increased. The theoretical basis and practical aspects of influencing prescribing have been reviewed." In general, administrative techniques, such as prescribing restrictions, mandatory consultations, or medical management protocols, positively affect prescribing patterns. However, these positive effects may be lost when the administrative program is discontinued. Educational programs ranging from printed, verbal, group, or individualized techniques have been assessed.' One study found that printed information alone does not influence subsequent prescribing." Our results support this finding. Our methodology did not investigate the prescribing practices of individual physicians, but rather the entire medical staff. Because our educational programs were aimed at the entire staff, educational benefit should have been obtained with all prescribers. We did not verify that all prescribers had received and reviewed the educational material. Feedback to individual prescribers has been shown to be beneficial in changing prescribing patterns; although sustained benefit is questionable. We did not provide any prescriber with direct information regarding his monitoring practices. Such methods would be required to optimize the monitoring of pentamidine and correct the deficiencies identified in our audits. A. MELANIE MARTINS, B.Sc.(pharrn.)
Staff Pharmacist (at time of writing) St. Paul's Hospital Vancouver. British Columhia Doctor ofPharmacy Student College ofPharmacy Ohio State University Columbus. Ohio 43210
5. Hershey C, Goldberg H, Cohen D. The effectof computerized feedback coupled with a newsletter upon outpatient prescribing charges. Med Care 1988;26:88-93.
Imipenem lcilastatin-associated hiccups TO THE EDITOR: Seizures are the most frequently observed neurologic adverse reactions following imipenem administration.'? We report a patient with no central nervous system disorders in whom persistent hiccups developed during imipenem/cilastatin (IIC) treatment. A 46-year-old mansustained an openfracture of his lefttibiainJanuary 1991 witha mowing machine. He wasadmitted to the orthopedic unitof University Hospital where he underwent several debriding procedures followed byexternal reduction of the tibia. Over the next few months, purulent drainage from the wound wasnotedthat persisted despite a specific antibiotic regimen. InOctober 1991. an X-ray showed osteomyelitis of thetibia with a sequestrum. Intheoperatingroom on November 18.the necrotic bonewascuretted andthewound packed open. Based on the results of a previous cultureandantibiogram that yielded a growth of multiple pathogens (Staphylococcus aureus,Enterococcus faecalis, two strains of Enterobacteraerogenes, and Aeromonashydrophilai, VC 1g iv infused over60 minutes q6handgentamicin 120mg iv infused over30 minutes q8hwere started. During infusion of the fourth doseof I/C.thepatient experienced nausea, vomiting. andpersistent hiccups. which continued during hissleep. Aftereachof thenextfourdoses. thehiccups worsened. On day3. thepatient awoke early and severe hiccups reappeared promptly afterthefirst morning dose, followed 30 minuteslaterbyvomiting of "coffee-ground" likematerial. Laboratory tests showed a decrease in hemoglobin from 100to 90 gIL. Serumcreatinine, urea,and electrolytes were within the normal range. Anendoscopic procedure wasperformed, which disclosed noabnormalities intheupper gastrointestinal tract. Ranitidine and metoclopramide were administered. The hiccups responded to a decrease in the VC dose to500mganddidnotrecur. The patient had no history of hiccups, abnormal renal function, or underlying central nervous system disease. We believe that a probable link can be established between this case and the use of lie at maximal doses, applying Karch and Lasagna criteria.' To our knowledge this adverse reaction has not been previously reported. No cause is apparent, although one possible explanation may be the loss of inhibition of higher neural centers' upon the hiccup-reflex arc caused by I/C's effects on the gamma-aminobutyric acid receptors in the brain," MARIBEL LUCENA, M.D. Professor ofPharmacology Department ofClinical Pharmacology University Hospital School ofMedicine 29080 Malaga Spain
RAUL ANDRADE, M.D. Professor ofMedicine Department ofGastroenterology
MARIA CABELLO, M.D. Fellow in Clinical Pharmacology Department ofClinical Pharmacology
ENCARNACION CLAVIJO. M.D. Professor of Microbiology Department ofMicrobiology
ENRIQUE QUEIPO DE LLANO, M.D. Head
Department ofOrthopaedic Surgery GLEN R. BROWN, Pharrn.D.
Assistant Director. Clinical Services St. Paul's Hospital
REFERENCES I. Drake S, Lampasona V, Nicks HL, Schwarzmann SW. Pentamidine isethionate in the treatment of Pneumocystis carinii pneumonia. Clin Pharm 1985;4:507-16.
2. Salamone FR, Cunha BA. Update on pentamidine for the treatmentof Pneumocystis carinii pneumonia. Clin Pharm 1988;7:501-10. 3. Raisch DW. A model of methodsfor influencing prescribing: part I. A reviewof prescribing models,persuasion theories, and administrative and educational methods. DICP Ann Pharmacother 1990;24:417-21. 4. Raisch DW. A model of methods for influencingprescribing: part II. A reviewof educational methods. theories of human inference, and delineationof the model. DICP Ann Pharmacother 1990;24:537-42.
REFERENCES I. Barza M. Imipenem: first of a new class of beta-lactarn antibiotics. Ann Intern Med 1985; 103:552-60. 2. Clissoid SP, Todd PA, Campoli-Richards DM. Imipenern/cilastatin. A reviewof its antibacterial activity, pharrnacokinetic properties and therapeuticefficacy. Drugs 1987;33:183-241. 3. Eng RHK, Munsif AN, Yangco BG, Smith SM, Chmel H. Seizure propensity with imipenem. Arch Intern Med 1989; 149:1881-3. 4. Karch FE, Lasagna L. Adversedrug reactions: a critical review.lAMA 1975;234: 1236-41. 5. Newsom-Davis J. An experimental study of hiccup. Brain 1970;93:85172. 6. Kamei C, Sunami A, Tasaka K. Epileptogenic activity of cephalosporins in rats and their structure-activity relationship. Epilepsia 1983; 24:431-9.
The Annals ofPharmacotherapy
•
1992 November, Volume 26 •
1459
