Continuation of pregnancy after first-trimester exposure to mifepristone: an observational prospective study.

OBJECTIVE: To report the follow-up of continuing pregnancies after first-trimester exposure to mifepristone. DESIGN: Observational prospective study. SETTING: France. SAMPLE: Patients exposed to mifepristone during the first 12 weeks of pregnancy. METHODS: Women were included in the study when they or their doctors asked a French pharmacovigilance centre or the Paris Teratogen Information Service about the risk of mifepristone exposure in early pregnancy. Exclusion criteria were requests received after 22 weeks of gestation or subsequent elective termination of pregnancy without a pathological examination of the fetus. Data on maternal history and drug exposure were collected on first contact, and pregnancy outcomes were documented at follow-up. MAIN OUTCOME MEASURES: Rate of major congenital malformations. RESULTS: A total of 105 pregnancies were included, with 46 exposed to mifepristone alone, and 59 exposed to both mifepristone and misoprostol. There were 94 live births (90.4%) and 10 (9.6%) miscarriages (including one with major malformation). Elective termination of pregnancy was performed after the subsequent diagnosis of trisomy 21 in one case. The overall rate of major congenital malformations was 4.2% (95% CI 1.2-10.4%), with two cases among 38 patients exposed to mifepristone alone, and two cases among 57 patients exposed to both mifepristone and misoprostol. CONCLUSIONS: This first prospective study found that the rate of major malformations after first-trimester exposure to mifepristone is only slightly higher than the expected 2-3% rate in the general population. Such findings provide reassuring data for risk evaluation for continuation of pregnancy after mifepristone exposure.

Respiratory depression following administration of intrathecal bupivacaine to an opioid-dependent patient.

OBJECTIVE: To document two cases of respiratory depression in patients receiving morphine once the stimulating effect of pain on respiration was removed by bupivacaine. CASE SUMMARIES: Case 1: A 72-year-old 84-kg white man with cancer of the bladder and bone metastases had intense back and leg pain that was treated with intrathecal morphine for 6 months at an increasing dosage up to 10 mg twice daily. The intrathecal route was avoided for 4 days because of a suspected local infection at the site of the intrathecal catheter. During this 4-day period the patient received extended-release morphine and subcutaneous morphine daily. When the intrathecal route was used again, he received an identical dose of morphine plus bupivacaine and epinephrine. Ten minutes after the injection, fatal respiratory distress occurred. Case 2: A 92-year-old white woman was admitted for revascularization of arteritis on her left leg. To treat a painful sacrum and heel bedsores, she received extended-release oral morphine for 8 days. Induction of the intrathecal anesthesia was performed with bupivacaine. After 10 minutes, the patient became subcomatose, with miosis and apnea. Intravenous naloxone restored spontaneous respiration and normal consciousness. CONCLUSIONS: Pain is a physiologic antagonist of the respiratory depressant effects of opioid analgesics. By reducing pain stimulation, bupivacaine may make patients more susceptible to opioid respiratory depression. Such situations require titration of bupivacaine and other analgesics as well as increased monitoring of the patient.

Long-term oxygen therapy at home. Compliance with medical prescription and effective use of therapy. ANTADIR Working Group on Oxygen Therapy. Association Nationale de Traitement à Domicile des Insuffisants Respiratories.

STUDY OBJECTIVE: Daily duration of oxygen administration is an important factor in the effectiveness of long-term oxygen therapy (LTOT) for hypoxic chronic pulmonary disease. We have assessed the daily use of oxygen therapy in 930 patients with COPD and examined factors associated with the effective use of this treatment. METHODS: Objective daily duration of oxygen use over a 3-month period was prospectively measured using the counter clock of the oxygen concentrators or by weighing the liquid oxygen container at each delivery. A questionnaire was filled in by an independent investigator asking about home situation, lifestyle, and whether oxygen therapy was used during all domestic and outside activities. In addition, prescribing physicians were asked about the duration and modalities of oxygen prescribed in each case. RESULTS: The patients had been receiving LTOT for 36 +/- 24 months and had hypoxemia (PaO2 = 56 +/- 9 mm Hg), hypercapnia (PaCO2 = 47 +/- 8 mm Hg), and severe airflow obstruction (FEV1/VC = 42 +/- 14%). The mean duration of oxygen treatment prescribed was 16 +/- 3 h/d. The mean duration of oxygen therapy achieved was 14.5 +/- 5 h, but only 45% of the patients achieved oxygen therapy for 15 h or more per day. Patients with effective use of LTOT, ie receiving oxygen therapy for at least 15 h/d, were significantly more hypoxic (PaO2 = 54 +/- 9 vs 57 +/- 9 mm Hg; p < 0.001), more hypercapnic (PaCO2 = 48 +/- 8 vs 46 +/- 7 mm Hg; p < 0.005), and also more obstructed (FEV1/VC = 39.5 +/- 13 vs 45 +/- 14%; p < 0.001) than the rest of the patients under treatment. Other factors associated with effective use of oxygen were (1) initial prescription for 15 h or more per day, (2) supplementary education on oxygen therapy by a nurse or physiotherapist, (3) cessation of smoking, (4) use of oxygen in all domestic situations (toilet, meals, leisure, etc.), and (5) absence of side effects from oxygen treatment. CONCLUSIONS: Attention by the prescribing physicians to such factors could optimize oxygen prescription and constitute goals for education of patients.