Comparison of the oral direct thrombin inhibitor ximelagatran with enoxaparin as prophylaxis against venous thromboembolism after total knee replacement: a phase 2 dose-finding study.

BACKGROUND: Up to one third of patients who undergo total knee replacement develop deep vein thrombosis after surgery despite receiving low-molecular-weight heparin prophylaxis. Ximelagatran is a novel direct inhibitor of free and clot-bound thrombin. METHODS: We performed a randomized, parallel, dose-finding study of 600 adults undergoing elective total knee replacement at 68 North American hospitals to determine the optimum dose of ximelagatran to use as prophylaxis against venous thromboembolism after total knee replacement. Patients received either ximelagatran twice daily by mouth in blinded fixed doses of 8, 12, 18, or 24 mg or open-label enoxaparin sodium, 30 mg, subcutaneously twice daily, starting 12 to 24 hours after surgery and continuing for 6 to 12 days. We measured the 6- to 12-day cumulative incidence of symptomatic or venographic deep vein thrombosis, symptomatic pulmonary embolism, and bleeding. RESULTS: A total of 594 patients received at least 1 dose of the study drug; 443 patients were evaluable for efficacy. Rates of overall venous thromboembolism (and proximal deep vein thrombosis or pulmonary embolism) for the 8-, 12-, 18-, and 24-mg doses of ximelagatran were 27% (6.6%), 19.8% (2.0%), 28.7% (5.8%), and 15.8% (3.2%), respectively. Rates of overall venous thromboembolism (22.7%) and proximal deep vein thrombosis or pulmonary embolism (3.1%) for enoxaparin did not differ significantly compared with 24-mg ximelagatran (overall difference, -6.9%; 95% confidence interval, -18.0% to 4.2%; P=.3). There was no major bleeding with administration of 24 mg of ximelagatran twice daily. CONCLUSION: Fixed-dose, unmonitored ximelagatran, 24 mg twice daily, given after surgery appears to be safe and effective oral prophylaxis against venous thromboembolism after total knee replacement.

Immunization of woodchucks (Marmota monax) with hepatitis delta virus DNA vaccine.

We investigated the DNA immunization approach in order to induce a protective immune response against hepatitis delta virus (HDV) superinfection of chronically woodchuck hepatitis virus (WHV) infected woodchucks. The animals were immunized with an expression vector encoding HDAg by gene gun. T cell and humoral immune responses induced by this protocol were determined and compared with those induced by HDAg immunization using a CpG oligonucleotide as an adjuvant. After immunization the woodchucks were challenged with 10(6) genome equivalents of HDV. The protein immunization with HDAg induced good humoral and T helper cell responses in the woodchucks, but did not protect them from HDV superinfection. The DNA immunized woodchucks were also not protected from HDV superinfection, however, the course of infection was modified: HDV viremia occurred later, the typical fluctuation of the HDV RNA titer with several peaks was absent, and antibodies to HDV were not detectable.

Esomeprazole once daily for 6 months is effective therapy for maintaining healed erosive esophagitis and for controlling gastroesophageal reflux disease symptoms: a randomized, double-blind, placebo-controlled study of efficacy and safety.

OBJECTIVE: Esomeprazole, the S-isomer of omeprazole, achieves a significantly greater healing rate and symptom resolution of erosive esophagitis than that achieved by omeprazole. The objective of this study is to assess the efficacy of the new proton pump inhibitor esomeprazole in preventing relapse over a prolonged period in patients with healed erosive esophagitis. METHODS: A total of 318 gastroesophageal reflux patients whose erosive esophagitis was healed in a comparative study of esomeprazole 40 mg, 20 mg, or omeprazole 20 mg, were randomized to maintenance therapy with once daily esomeprazole 40 mg, 20 mg, or 10 mg, or placebo in a U.S., double-blind multicenter trial. RESULTS: After 6 months, healing was maintained (cumulative life table rates) in 93.6% (95% CI 87.4-99.7) of patients treated with esomeprazole 40 mg, 93.2% (95% CI 87.4-99.0) treated with esomeprazole 20 mg, and 57.1% (95% CI 45.2-69) treated with esomeprazole 10 mg; p < 0.001 vs placebo (29.1%; 95% CI 17.7-40.3). Of patients relapsing, mean time to first recurrence of esophagitis increased with dose, from 34 days (placebo) to 78 days (10 mg), 115 days (20 mg), and 163 days (40 mg). Patients treated with esomeprazole had less frequent and less severe heartburn than those treated with placebo. At month 6, more than 70% of patients being treated with esomeprazole remained symptom-free. CONCLUSIONS: Esomeprazole is effective and well tolerated in the maintenance of a healing erosive esophagitis. Esomeprazole 40 mg and 20 mg maintain healing in over 90% of patients while providing effective control of heartburn symptoms.

The effects of providing therapists with feedback on patient progress during psychotherapy: are outcomes enhanced?

Patient-focused research attempts to provide information that answers the question: Is this treatment benefiting this patient? Although several systems have been developed to monitor and provide feedback about a patient's response to psychotherapy, few if any have been tested empirically. The current study divided 609 patients into four groups (two experimental and two control) to determine if feedback regarding patient progress, when provided to a therapist, affected patient outcome and number of sessions attended. Results showed that feedback increased the duration of treatment and improved outcome relative to patients in the control condition who were predicted to be treatment failures. Twice as many patients in the feedback group achieved clinically significant or reliable change and one-third as many were classified as deteriorated by the time treatment ended. For those patients who were predicted to have a positive response to treatment, feedback to therapists resulted in a reduction in the number of treatment sessions without reducing positive outcomes.

Esomeprazole improves healing and symptom resolution as compared with omeprazole in reflux oesophagitis patients: a randomized controlled trial. The Esomeprazole Study Investigators.

BACKGROUND: The pharmacologic profile of the new proton pump inhibitor esomeprazole has demonstrated advantages over omeprazole that suggest clinical benefits for patients with acid-related disease. METHODS: 1960 patients with endoscopy-confirmed reflux oesophagitis (RO) were randomized to once daily esomeprazole 40 mg (n=654) or 20 mg (n=656), or omeprazole 20 mg (n=650), the standard recommended dose for RO, for up to 8 weeks in a US, multicentre, double-blind trial. The primary efficacy variable was the proportion of patients healed at week 8. Secondary variables included healing and heartburn resolution at week 4, time to first resolution and sustained resolution of heartburn, and per cent of heartburn-free days and nights. Safety and tolerability were also evaluated. RESULTS: Significantly more patients were healed at week 8 with esomeprazole 40 mg (94.1%) and 20 mg (89.9%) vs. omeprazole 20 mg (86.9%), using cumulative life table estimates, ITT analysis (each P < 0.05). Esomeprazole 40 mg was also significantly more effective than omeprazole for healing at week 4 and for all secondary variables evaluating heartburn resolution. The most common adverse events in all treatment groups were headache, abdominal pain and diarrhoea. CONCLUSION: Esomeprazole was more effective than omeprazole in healing and symptom resolution in GERD patients with reflux oesophagitis, and had a tolerability profile comparable to that of omeprazole.

Efficacy of omeprazole for the treatment of symptomatic acid reflux disease without esophagitis.

BACKGROUND: Up to three quarters of patients with gastroesophageal reflux disease (GERD) have symptoms, such as heartburn, but no macroscopic evidence of erosive esophagitis, making symptomatic GERD a common clinical problem in the primary care setting. OBJECTIVE: To compare the efficacy and safety of omeprazole, 20 mg once daily; omeprazole, 10 mg once daily; and placebo in the treatment of symptomatic GERD without erosive esophagitis. METHODS: Patients with a history of heartburn (> or =12 months) and episodes of moderate to severe heartburn on 4 or more of the 7 days before endoscopy were eligible to participate in this 4-week, randomized, double-blind, placebo-controlled trial. The absence of erosive esophagitis was established through endoscopy. Eligible patients were randomized to 1 of 3 treatment groups: omeprazole, 20 mg once daily; omeprazole, 10 mg once daily; or placebo. Patients were assessed at weeks 2 and 4. The efficacy of omeprazole for the treatment of heartburn was determined mainly through the following diary card data: daily resolution of heartburn and complete resolution of heartburn every day during 1 week of treatment. The efficacy of omeprazole for the treatment of acid regurgitation, dysphagia, epigastric pain, and nausea was also assessed. RESULTS: Of 359 randomized patients, 355 were included in the statistical analysis (intention-to-treat population). Daily proportions of patients with no heartburn were consistently greater in the 20-mg omeprazole group (62%, day 7; 74%, day 27) than in the 10-mg omeprazole group (41%, day 7; 49%, day 27) or the placebo group (14%, day 7; 23%; day 27). Complete resolution of heartburn every day during the last treatment week was significantly (P< or =.002) higher in the 20-mg omeprazole group (48%) than in the 10-mg omeprazole (27%) or placebo (5%) group. Omeprazole was significantly (P< or =.003) more effective than placebo for the treatment of acid regurgitation, dysphagia, epigastric pain, and nausea. CONCLUSIONS: Patients with symptomatic GERD require profound acid suppression to achieve symptomatic relief. Omeprazole, 20 mg once daily, was superior to omeprazole, 10 mg once daily, and to placebo in providing early and sustained resolution of heartburn, as well as treatment of other troublesome GERD symptoms.

The effect of parent training in music and multimodal stimulation on parent-neonate interactions in the neonatal intensive care unit.

This study examined the effects of parent training in music and multimodal stimulation on the quantity and quality of parent-neonate interactions and the weight gain and length of hospitalization of premature and low birthweight (LBW) infants in a Neonatal Intensive Care Unit (NICU). Twenty sets of parents and premature LBW infants participated in the study. Parents in the experimental group (n = 10) received approximately one hour of instruction in appropriate uses of music, multimodal stimulation including massage techniques, and signs of infant overstimulation and techniques for its avoidance. Parent-neonate interactions, specifically parent actions and responses and infant stress and nonstress behaviors, were observed for subjects in both groups. Infant stress behaviors were significantly fewer and appropriateness of parent actions and responses were significantly greater for experimental infants and parents than for control subjects. Parents in the experimental group also self-reported spending significantly more time visiting in the NICU than did parents of control infants. In addition, length of hospitalization was shorter and average daily weight gain was greater for infants whose parents received training, although these differences were not significant. A one month, postdischarge follow-up showed little difference between experimental and control group parent-infant interactions in the home.

Testing a model of long-term alliance success.

The remarkable consistency of buyer and supplier perspectives was the most striking feature of this research. Although significant differences did exist, the dominant perspective illustrated a strong cohesion between partners. AS such, it would appear that these alliances do represent "best in class" relationships and thus may provide valuable insight for academics and practitioners into what makes alliances succeed--or fail.

Comparison of once-daily doses of omeprazole (40 and 20 mg) and placebo in the treatment of benign gastric ulcer: a multicenter, randomized, double-blind study.

OBJECTIVE: The purpose of this multicenter, randomized, double-blind study, conducted in 520 patients, was to compare the efficacy and safety of omeprazole (40 and 20 mg once daily) with placebo in the treatment of benign gastric ulcer. METHODS: Treatment with omeprazole or placebo lasted 4 wk; those whose ulcers remained unhealed continued the same treatment regimen for an additional 4 wk. The effects of therapy were determined by endoscopy and assessment of GI symptoms. Safety and tolerability were evaluated through reported adverse events, physical examinations, and laboratory tests. RESULTS: At weeks 4 and 8, the proportion of patients with healed ulcers was significantly greater in the omeprazole 40- and 20-mg groups than in the placebo group (p < 0.01). At week 8, the healing rate was significantly greater in the 40-mg group than in the 20-mg group (82.7 vs 74.8%, p < 0.05). In patients with large ulcers (>1 cm), the 40-mg regimen was associated with a significantly higher healing rate (78.9%) than both the 20-mg regimen (61.4%) and placebo (34.6%) at week 8 (p < 0.05 vs omeprazole 20 mg; p < 0.01 vs placebo). Healing rates in patients with small ulcers were similar for the 40- and 20-mg groups. Omeprazole was well tolerated, with no significant differences versus placebo in the overall incidence of clinical or laboratory adverse events. CONCLUSIONS: Omeprazole 40 and 20 mg, administered once daily, healed a significantly greater proportion of patients than did placebo. The 40-mg regimen offered significant advantages over the 20-mg regimen in patients with large ulcers.

Analysis of pain management in critically ill patients.

We analyzed the adequacy of pain control for 17 trauma patients during the initial part of their stay in the intensive care unit, and assessed reasons for inadequate analgesia, if it occurred. Patients, and physicians, and nurses were interviewed. A verbal pain intensity scale was used to determine whether patients received adequate analgesia. Patients were asked if the pain hindered their activities, and whether they requested pain medication from their caregivers. Caregivers were questioned whether patients received adequate analgesia. Prescribed morphine regimens and the amount of narcotic administered were analyzed. Twenty-seven percent of patients rated pain intensity as moderate and 47% as severe. Ninety-five percent of housestaff and 81% of nurses reported the patients received adequate pain control. Forty-seven percent of the patients who had moderate or severe pain asked their physician for more pain medication, and 65% asked the nurse. Thirteen residents did not order a larger dose of morphine due to concern about respiratory depression or hypotension. Morphine dosages ranged from 1-8 mg intravenously every 1-2 hours as necessary. Nurses administered less than the maximum amount ordered 58% of the time. The mean dosing interval was 2.3 hours. Barriers to adequate pain management were disparity in the perception of pain between patients and caregivers; patients not requesting more analgesia despite despite the presence of moderate to severe pain; and physician and nurse concerns about patients' adverse physiologic response to increased dosages.

Lisinopril versus placebo in the treatment of heart failure: the Lisinopril Heart Failure Study Group.

Lisinopril, a long-acting, angiotensin-converting enzyme inhibitor, was compared with placebo in a randomized, parallel, double-blind, 12-week study of 193 patients with heart failure. All patients were New York Heart Association Functional Class II, III, or IV and had remained symptomatic despite optimal dosing with digoxin and diuretics. After 12 weeks of therapy, the improvement in treadmill exercise duration was greater in the lisinopril group (113 seconds) compared with the placebo group (86 seconds). This improvement in exercise duration was particularly evident in patients with left ventricular ejection fractions less than 35% (lisinopril = 130 seconds; placebo = 94 seconds). In patients receiving lisinopril, the increase in exercise duration was accompanied by an improvement in quality of life as measured by the Yale Scale Dyspnea/Fatigue Index and in signs and symptoms of heart failure. In addition, the lisinopril group had a larger mean increase (3.7%) in left ventricular ejection fraction when compared with the placebo group (1.3%). Thus, lisinopril, administered once daily for 12 weeks, was well tolerated and efficacious in the treatment of heart failure when used concomitantly with diuretics and digoxin.

Current patterns of prescribing and administering morphine in trauma patients.

We attempted to characterize the current prescribing practices and administration patterns for intravenous intermittent morphine in trauma patients in a multicenter, open prospective, observational study. The subjects were 141 patients admitted to the surgical intensive care units (ICU) of five United States trauma centers within 12 hours of injury who received intermittent intravenous morphine for pain relief. The study was conducted from April 15, 1992, to February 15, 1993. Data obtained during the first 32 hours of the ICU stay included morphine regimen, doses administered, and time between doses. One hundred sixty-one orders were prescribed by surgeons. The most frequently ordered dose was 2-4 mg and the most frequently ordered interval was every hour as necessary. There was no relationship between the severity of injury and the minimum dose ordered. During the 492 nursing shifts studied, 1257 doses were administered. Of these, 44% were at or below the minimum amount prescribed by the surgeons. Thirty-three percent of the patients received a dose at an interval of more than 3 hours. We concluded that small amounts of narcotic analgesics are given to severely injured patients, and amount ordered is not affected by the severity of injury.

Effect of analgesic treatment on the physiological consequences of acute pain.

Physiological responses to acute pain are described, and the effects of different analgesic techniques on these responses are discussed. The body's response to acute pain can cause adverse physiological effects. Pain can impede the return of normal pulmonary function, modify certain aspects of the stress response to injury, and alter hemodynamic values and cardiovascular function. It can produce immobility and contribute to thromboembolic complications. In addition, pain can slow a patient's recovery from surgery and contribute to increased morbidity. Fewer pulmonary complications occur when adequate analgesia is provided through the use of epidural narcotics and local anesthetics, particularly if the injury or surgery involves the lower part of the body. Continuous morphine infusions, intercostal nerve blocks, and transcutaneous electrical stimulation do not alter the frequency of pulmonary complications. The effectiveness of patient-controlled analgesia in reducing postoperative pulmonary complications is still not known. Epidural local anesthetic therapy inhibits the stress response, particularly in operations involving the lower abdomen or extremities; this technique is less effective during major abdominal procedures. Suppression of endocrine-metabolic changes following lower abdominal surgery requires neural block to the fourth thoracic segment. Epidural narcotics partially inhibit the stress response after lower abdominal or extremity surgery but not after upper abdominal or thoracic surgery. Local anesthetics applied to the surgical site, intercostal nerve blocks, and intrapleural and intraperitoneal administration also do not modify the stress response. Adequate analgesia through the use of local anesthetics and narcotics postoperatively generally results in improved cardiovascular function, decreased pulmonary morbidity and mortality, earlier ambulation, and decreased likelihood of deep vein thrombosis. Some data suggest that improved patient outcome occurs with adequate analgesia. Block of afferent and efferent neural pathways by local anesthetics seems to be the most effective analgesic modality in lessening the physiologic response to pain and injury.

Identification of patient-controlled analgesia overdoses in hospitalized patients: a computerized method of monitoring adverse events.

OBJECTIVE: To describe and validate a computer-based quality assurance method that detects narcotic overdoses associated with patient-controlled analgesia (PCA) use. SETTING: Two acute care teaching hospitals. PATIENTS: 4669 patients who received PCA. INTERVENTIONS: The following patient lists were obtained during a two-year period from both hospital information systems: those who received PCA and (1) received naloxone, a narcotic antagonist, (2) were transferred to an intensive care unit, (3) had a cardiac or respiratory arrest, or (4) died. Possible overdoses were defined as patients who appeared on the PCA list and one of the other lists. Charts were reviewed if the patient's name appeared on the PCA and one of the other lists. Patients were judged to have experienced a narcotic overdose if there was an immediate improvement in blood pressure, respiratory rate, or mental status after the administration of naloxone. RESULTS: The search strategy identified 294 possible overdoses in 1499 patients who received PCA. Ten charts were unavailable for review. An actual overdose occurred in 11 patients. The accuracy of the new method was compared with that of the hospitals' present reporting methods. Eleven overdoses were identified by the computer search, but only 6 overdoses were identified in incident and adverse drug reaction reports. CONCLUSIONS: The systematic computer search identified almost twice as many adverse incidents than were reported by the traditional hospital methods.

Difficulties in diagnosing narcotic overdoses in hospitalized patients.

OBJECTIVE: To describe the clinical presentation of narcotic overdose in hospitalized patients and to differentiate this circumstance from other conditions often misdiagnosed as overdose. DESIGN: Case series. SETTING: Two acute-care teaching hospitals. PATIENTS: Forty-three hospitalized patients who received naloxone for a clinically suspected narcotic overdose. INTERVENTIONS: Two investigators independently evaluated each incident to determine whether the patient had a narcotic overdose. The patients were judged to have had an overdose if caregivers documented an immediate improvement in mental status, respiratory rate, or blood pressure after naloxone administration. MEASUREMENTS: The clinical presentation of a narcotic overdose in hospitalized patients was defined. Conditions misdiagnosed as an overdose were determined. MAIN RESULTS: Symptoms improved rapidly with the administration of naloxone in 28 incidents (65 percent) and were designated overdose. In 15 other instances there was no improvement in symptoms; these patients were designated nonoverdose. Only half of the overdose patients had a respiratory rate < 8 breaths/min immediately prior to naloxone administration. Only two of the overdose patients had the classic triad of symptoms (respiratory depression, coma, and pinpoint pupils). Other overdose patients had only one or two of the classic signs. The clinical presentation of narcotic overdoses in hospitalized patients did not include respiratory depression, hypotension, or coma in the majority of patients. All overdose patients showed a decrease in mental status. The majority of nonoverdose patients had pulmonary conditions that were misdiagnosed as a narcotic overdose. CONCLUSIONS: Narcotic overdoses in hospitalized patients seldom fit the classic description. The lack of respiratory depression does not mean the absence of a narcotic overdose. Patients who receive narcotics and develop a significant decrease in mental status should be evaluated for a possible overdose. Pulmonary, neurologic, cardiovascular, and electrolyte abnormalities often are misdiagnosed as a narcotic overdose in hospitalized patients.

Pharmacokinetic evaluation of a new oral cyclosporine formulation.

STUDY OBJECTIVE: To compare the pharmacokinetics of a new oral cyclosporine preparation with those of cyclosporine solution diluted in Isocal and the intravenous formulation. DESIGN: Randomized, crossover trial. SETTING: Tertiary care referral center. PATIENTS: Seven pediatric liver transplant recipients who were receiving oral cyclosporine as part of their immunosuppressive regimen. All patients completed the study. INTERVENTIONS: Pharmacokinetic studies were performed with the intravenous and oral dosage forms. Patients received one dose of intravenous cyclosporine, and then were randomized to receive their usual oral cyclosporine dose incorporated into a chocolate wafer or mixed with Isocal. After a minimum of 3 days, the alternative preparation was administered. Serial cyclosporine blood samples were collected at predetermined intervals for 12 hours after the third dose for each regimen. Concentrations were determined by high-performance liquid chromatography. The data for the three dosage forms were fit simultaneously with a two-compartment model. MEASUREMENTS AND MAIN RESULTS: No difference was seen in F, ka, Cmax, and tmax between the two oral cyclosporine preparations (p > 0.05). No new rejection episodes occurred during the study period. CONCLUSIONS: We conclude there is no difference in the bioavailability of the oral solution and the chocolate formulation. We believe the new preparation may increase patient compliance and ensure administration of a complete dose compared with the currently marketed solution.

Chromatophoromas and chromatophore hyperplasia in Pacific rockfish (Sebastes spp.).

Pacific rockfish from Cordell Bank, off central California (United States), were collected and histologically examined from 1985 to 1990. Hyperplastic and neoplastic cutaneous lesions, involving dermal chromatophores, were observed in five species; yellowtail rockfish (Sebastes flavidus), bocaccio (S. paucispinis), olive rockfish (S. serranoides), widow rockfish (S. entomelas), and chilipepper rockfish (S. goodei). Yearly prevalences were highest in S. paucispinis (29-38%). Prevalence was initially low in S. flavidus, but increased more than 3-fold from 1985 (7.5%) to 1990 (25%). The majority of lesions were black, but white, yellow, orange, red, and mixed-color variants were also seen. Lesions were found in skin, fins, lips, gingiva, tongue, urogenital papilla, conjunctiva, and cornea of the eye. Flat lesions were consistent with melanophore (black), xanthophore (yellow or orange), and erythrophore (red) hyperplasia. Neoplastic lesions included melanophoromas, amelanotic melanophoromas, xanthophoromas, erythrophoromas, and mixed chromatophoromas. Although etiology has not been determined, interest is currently focused on potential exposure to chemical and radioactive carcinogens from the Farallon Island Radioactive Waste Dump, 30 km to the south.

Glucose response to abrupt initiation and discontinuation of total parenteral nutrition.

Plasma glucose was studied during the initiation of total parenteral nutrition (TPN) and the discontinuation of TPN without a tapering schedule. Blood was sampled every 5 minutes for 2 hours after the start of TPN and 1 week later as TPN was discontinued. A total of 14 initiations and 14 discontinuations were studied in 18 patients. Severity of illness in patients ranged from stable condition postoperatively to multiple-system failure; six patients had diabetes mellitus. The TPN solution was a 3:1 admixture that provided a caloric intake equal to 1.2 times the resting energy expenditure, with 40% fat and 60% carbohydrate calories. An average of 1963 kcal was provided per day (340 g of glucose, 79 g of fat). During the initiation phase, the mean increase in plasma glucose was 60 mg/dL. The increase for diabetic patients was 79 +/- 14 mg/dL compared with 52 +/- 23 mg/dL for the nondiabetics. During the discontinuation phase, the mean plasma glucose decreased 40 +/- 20 mg/dL; two patients with high concentrations of regular insulin (50 and 100 units) showed an increase in plasma glucose when the TPN was stopped. Plasma glucose returned to the preinfusion baseline after discontinuation. During both initiation and discontinuation, plasma glucose showed little change after the first 60 minutes. No clinical symptoms of hypoglycemia were observed. In conclusion, TPN as a 3:1 admixture can be safely started as full nutrition support and stopped abruptly without a tapering schedule. Plasma glucose response is rapid, predictable, and mostly complete within 60 minutes.

Narcotic use in the hospital: reasonably safe?

OBJECTIVE: To determine the causes and frequency of overdoses associated with the administration of opioid analgesics in hospitalized patients. DESIGN: Case series. SETTING: Two acute care teaching hospitals. PATIENTS: Eighty-one hospitalized patients who received naloxone for a clinically suspected narcotic overdose. INTERVENTIONS: Three investigators reviewed each patient who received naloxone during a 12-month period. The patients were judged to have a narcotic overdose if caregivers documented an immediate improvement in mental status, respiratory rate, or blood pressure after naloxone administration. MAIN OUTCOME MEASURES: The number and causes of narcotic overdoses were determined. The frequency of morphine and meperidine overdoses was calculated. The number of incidents reported using incident or adverse drug reaction reports or the appropriate International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code. RESULTS: In the 22 overdoses that occurred, 14 (64 percent) were caused by medication prescribing, compounding, or administration errors and potentially were preventable. The remaining eight patients experienced an overdose despite receiving appropriate amounts of opioids. The frequency of overdoses was 0.4 and 0.2 percent of total patients receiving morphine or meperidine, respectively, at the two hospitals. Nonreporting of these narcotic overdoses was frequent. In one hospital, 1 incident report and 3 adverse drug reactions were reported for 17 overdoses. At the second hospital, 1 incident report and 1 adverse drug reaction were reported for 6 overdoses. None of the patient charts included an ICD-9-CM code that documented the problem. CONCLUSIONS: The causes of overdoses are not limited to prescribing and administration errors. Some patients, despite proper execution of appropriate orders, develop a narcotic overdose. Caregivers must be aware of this problem and monitor patients for a decrease in mental status and respiratory rate. In addition, we conclude that an important number of hospitalized patients develop an overdose even though the frequency is low related to the number of patients receiving narcotics.