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PubMed2004

Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial.

CONTEXT: Despite decades of use and considerable research, the role of estrogen alone in preventing chronic diseases in postmenopausal women remains uncertain. OBJECTIVE: To assess the effects on major disease incidence rates of the most commonly used postmenopausal hormone therapy in the United States. DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blind, placebo-controlled disease prevention trial (the estrogen-alone component of the Women's Health Initiative [WHI]) conducted in 40 US clinical centers beginning in 1993. Enrolled were 10 739 postmenopausal women, aged 50-79 years, with prior hysterectomy, including 23% of minority race/ethnicity. INTERVENTION: Women were randomly assigned to receive either 0.625 mg/d of conjugated equine estrogen (CEE) or placebo. MAIN OUTCOME MEASURES: The primary outcome was coronary heart disease (CHD) incidence (nonfatal myocardial infarction or CHD death). Invasive breast cancer incidence was the primary safety outcome. A global index of risks and benefits, including these primary outcomes plus stroke, pulmonary embolism (PE), colorectal cancer, hip fracture, and deaths from other causes, was used for summarizing overall effects. RESULTS: In February 2004, after reviewing data through November 30, 2003, the National Institutes of Health (NIH) decided to end the intervention phase of the trial early. Estimated hazard ratios (HRs) (95% confidence intervals [CIs]) for CEE vs placebo for the major clinical outcomes available through February 29, 2004 (average follow-up 6.8 years), were: CHD, 0.91 (0.75-1.12) with 376 cases; breast cancer, 0.77 (0.59-1.01) with 218 cases; stroke, 1.39 (1.10-1.77) with 276 cases; PE, 1.34 (0.87-2.06) with 85 cases; colorectal cancer, 1.08 (0.75-1.55) with 119 cases; and hip fracture, 0.61 (0.41-0.91) with 102 cases. Corresponding results for composite outcomes were: total cardiovascular disease, 1.12 (1.01-1.24); total cancer, 0.93 (0.81-1.07); total fractures, 0.70 (0.63-0.79); total mortality, 1.04 (0.88-1.22), and the global index, 1.01 (0.91-1.12). For the outcomes significantly affected by CEE, there was an absolute excess risk of 12 additional strokes per 10 000 person-years and an absolute risk reduction of 6 fewer hip fractures per 10 000 person-years. The estimated excess risk for all monitored events in the global index was a nonsignificant 2 events per 10 000 person-years. CONCLUSIONS: The use of CEE increases the risk of stroke, decreases the risk of hip fracture, and does not affect CHD incidence in postmenopausal women with prior hysterectomy over an average of 6.8 years. A possible reduction in breast cancer risk requires further investigation. The burden of incident disease events was equivalent in the CEE and placebo groups, indicating no overall benefit. Thus, CEE should not be recommended for chronic disease prevention in postmenopausal women.

Aged↗

PubMed2001

Approval summary: gemtuzumab ozogamicin in relapsed acute myeloid leukemia.

PURPOSE: Gemtuzumab ozogamicin (Mylotarg; Wyeth Laboratories, Philadelphia, PA) consists of a semisynthetic derivative of calicheamicin, a cytotoxic antibiotic linked to a recombinant monoclonal antibody directed against the CD33 antigen present on leukemic myeloblasts in most patients with acute myeloid leukemia (AML). In this study, we review the preclinical and clinical profiles of this immunoconjugate and the regulatory review that led to marketing approval by the United States Food and Drug Administration. EXPERIMENTAL DESIGN: From the literature and manufacturer's data, we review the activity, tolerability, and pharmacokinetics of gemtuzumab ozogamicin in preclinical and Phase I studies and its activity, efficacy, and side effects in three Phase 2 trials of 142 patients with relapsed AML. RESULTS: In Phase I studies, the major toxicity was myelosuppression, especially neutropenia and thrombocytopenia, resulting from the expression of CD33 on myeloid progenitor cells. The Phase 2 dose was 9 mg/m(2) infused i.v. over 4 h, repeated on day 14. A minority of patients experienced acute infusion-related symptoms, usually transient and occasionally requiring hospitalization. The complete response (CR) rate with full recovery of hematopoiesis was 16%. A subset of patients [CRs with incomplete platelet recovery (CRps)] was identified with blast clearance and neutrophil recovery but incomplete platelet recovery. The duration of responses of CRps appeared to be similar to those of the CRs, although the numbers were small. The question of the equivalence of these response groups was a central issue in the review of this new drug application (NDA). After considerable discussion, the Oncology Drugs Advisory Committee recommended allowing inclusion of CRps resulting in an overall response rate in the Phase 2 studies of 30%. In the subgroup of patients over 60 years of age, the overall response rate was 26%. Response duration was difficult to establish because of the high prevalence of postremission therapies. Tolerability and ease of administration may be improved compared with conventional chemotherapy, except for hepatotoxicity, with 31% of patients exhibiting abnormal liver enzymes. One patient died of liver failure in the Phase 2 trials. CONCLUSIONS: Marketing approval of gemtuzumab ozogamicin was granted on May 17, 2000 by the United States Food and Drug Administration under the Accelerated Approval regulations. Gemtuzumab ozogamicin is indicated for the treatment of patients with CD33 positive AML in first relapse who are 60 years of age or older and who are not considered candidates for cytotoxic chemotherapy. The approved dose was 9 mg/m(2) i.v. over 4 h and repeated in 14 days. Completion of the ongoing studies of gemtuzumab ozogamicin in relapsed AML and initiation of randomized clinical trials comparing the effects of gemtuzumab ozogamicin in combination with conventional induction chemotherapy to conventional chemotherapy alone on survival are mandated to confirm clinical benefit under the accelerated approval Subpart H regulations. Postmarketing reports of fatal anaphylaxis, adult respiratory distress syndrome (ARDS), and hepatotoxicity, especially venoocclusive disease (VOD) in patients treated with gemtuzumab ozogamicin, with and without associated hematopoietic stem cell transplantation (HSCT), have required labeling revisions and the initiation of a registration surveillance program. Tumor lysis and ARDS have been reported in patients with leukocytes above 30,000/ml treated with gemtuzumab ozogamicin; therefore, the reduction of leukocyte counts to below 30,000/ml is recommended prior to treatment. Patients should be carefully monitored for acute hypersensitivity, hypoxia, and delayed hepatotoxicity following treatment with gemtuzumab ozogamicin.

Adolescent↗

PubMed1995

[A comparative study of the efficacy of lisinopril versus quinapril in controlling light to moderate arterial hypertension. A follow-up with ABPM].

OBJECTIVE: To compare the antihypertensive efficacy of lisinopril versus quinapril given 20 mg once daily for the treatment of mild to moderate arterial hypertension (I-II WHO grades) using ambulatory blood pressure monitoring. This study also investigated the tolerance, adverse effects and changes in haematological or biochemical parameters with both drugs. METHODS: Fifty patients (men and women) with a range of age between 18 to 75 years were included in this open, randomized study to assess the hypotensive efficacy of lisinopril versus quinapril after 2 months of treatment, using ambulatory blood pressure monitoring (ABPM). To study data obtained from ABPM Mc Call curves were used and statistical analysis was made using Epistat programme. Covariance and Chi-square test were used for the comparative analysis of different variables, considering as statistically significant the value p < 0.05. Graphics were made using Lotus 123, V 3.0 version. All patients gave their informed consent to participate in the study. The protocol was approved by the Ethical Committee of the Clínico Hospital. RESULTS: Systolic blood pressure decreased from 172.6 to 152.6 mmHg in the lisinopril group (p < 0.001) and from 171.6 to 147 mmHg in the quinapril group (p < 0.001). Diastolic blood pressure decreased from 105.6 to 86.8 mmHg in the lisinopril group (p < 0.001) and from 106.1 to 88.1 mmHg in the quinapril group (p < 0.05). Using ABPM mean systolic blood pressure decreased from 157.3 to 126.5 mmHg with lisinopril (p < 0.001) and from 148 to 137.4 mmHg with quinapril (p < 0.05). Mean diastolic blood pressure decreased from 93.6 to 81.7 mmHg with lisinopril (p < 0.001) and from 89.4 to 85.9 with quinapril (p < 0.05). Decreases in basal glycemia were found from 0.996 to 0.878 in quinapril group (p < 0.05), total quinapril cholesterol in both groups (from 228.7 to 207.2 with lisinopril and from 247.4 to 225.7 with quinapril) (p < 0.05) and cholesterol-LDL in the quinapril group (180.1 to 152.1) (p < 0.05). CONCLUSIONS: Both drugs produce a fall of blood pressure in mild-to-moderate hypertension, although using ABPM this fall is more significant with Lisinopril. According to Mc Call index 73.4% of patients in the lisinopril group and 62.7% of quinapril group controlled their hypertension, and a difference found between BP values obtained in the clinic and those obtained using ABPM.

Adolescent↗

PubMed2026

Chemoradiotherapy versus short-course radiotherapy for response-adapted organ preservation in early-stage and intermediate-stage rectal cancer (STAR-TREC): 12-month results of an international, multicentre, open-label, parallel-group, randomised, phase 2/3 trial.

BACKGROUND: Total mesorectal excision (TME) is the standard treatment for most early-stage and intermediate-stage rectal cancer but can cause substantial perioperative morbidity, functional impairment, and reduced quality of life. We assessed whether long-course chemoradiotherapy (LCCRT) or short-course radiotherapy (SCRT) could increase organ preservation and reduce surgery, toxicity, and quality-of-life harms without compromising oncological outcomes. METHODS: STAR-TREC is an international, multicentre, open-label, parallel-group, randomised, phase 2/3 trial in five European countries. Eligible patients were aged 16 years or older in the UK or aged 18 years or older elsewhere, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and rectal adenocarcinoma (≤40 mm staged as mrT1-T3bN0). In phase 2, participants were randomly assigned (1:1:1) to LCCRT-based organ preservation (LCCRT-OP; 50 Gy in 25 fractions plus oral capecitabine 825 mg/m2 twice daily), SCRT-based organ preservation (SCRT-OP; 25 Gy in five fractions), or primary TME. Phase 2 assessed feasibility, with recruitment at months 12 and 24 as the primary endpoint and feasibility thresholds of four or more and six or more randomisations per month, respectively. Phase 3 adopted a partially randomised patient-preference design, allowing participants to choose either organ preservation or TME. Participants that chose organ preservation were randomly assigned (1:1) to receive LCCRT-OP or SCRT-OP using centralised, computer-generated assignment, with stratification by country and MRI T category (≤T3a vs T3b) using minimisation. The phase 3 primary endpoint was organ-preservation 30 months after treatment initiation, defined as absence of TME, stoma, or local recurrence, which was assessed in the modified intention-to-treat population, which included participants in phase 2 and phase 3. After a planned interim analysis of unmasked phase 2 data, the trial steering committee and independent data monitoring committee recommended reporting a 12-month, modified intention-to-treat analysis of implementation outcomes for participants recruited before Aug 8, 2023. This study is registered with ISRCTN (14240288) and is closed. FINDINGS: Between June 14, 2017, and April 8, 2024, 503 participants were enrolled at 37 sites. Phase 2 enrolled 120 participants, with recruitment rates of three and six participants per month at months 12 and 24, respectively. Overall, 12-month TME-free survival was 60% (47 of 78 participants). After phase 3 recruitment ended, interim analysis of unmasked phase 2 data showed an early TME-free survival benefit with LCCRT versus SCRT (12-month median TME-free survival not reached [95% CI not reached-not reached] vs 7·6 months [95% CI 6·4-not reached]; hazard ratio [HR] 3·7 [95% CI 1·7-8·0]; posterior probability of superiority >99·5%). The trial steering committee and independent data monitoring committee therefore recommended expanded analysis of 426 participants recruited before Aug 8, 2023: 120 from phase 2 and 306 from phase 3. 17 participants withdrew before treatment, leaving 409 in the modified intention-to-treat population: 163 allocated to LCCRT, 168 to SCRT, and 78 to primary TME. 116 (28%) participants were female and 293 (72%) were male. Among participants who opted for organ preservation, 12-month TME-free survival was 78·5% (95% CI 72·4-85·1) with LCCRT and 60·6% (53·6-68·4) with SCRT (HR 1·90 [95% CI 1·29-2·81]). The most common grade 3-4 serious adverse events were gastrointestinal disorders (four [2%] with LCCRT vs six [4%] with SCRT vs six [8%] with TME) and procedural complications (three [2%] with LCCRT vs five [3%] with SCRT vs five [6%] with TME). One participant allocated to primary TME died after an anastomotic leak. INTERPRETATION: These early results support a response-adapted organ-preservation approach, with LCCRT appearing more effective than SCRT at 12 months. Organ-preservation might also reduce treatment-related toxicity compared with primary TME. Longer follow-up is needed for the prespecified 30-month endpoint and definitive functional and oncological outcomes. FUNDING: Cancer Research UK, Stand Up to Cancer, Dutch Cancer Society, Danish Cancer Society, Kom Op Tegen Kanker, Cancerfonden, ALF Region Stockholm, RCC Region Stockholm.

Humans↗

PubMed1997

Management of newly diagnosed non-insulin-dependent diabetes mellitus in the primary care setting: effects of 2 years of gliclazide treatment--the Diadem Study.

Five thousand five hundred seventy-two newly diagnosed non-insulin-dependent diabetes mellitus (NIDDM) patients (3,225 men and 2,347 women; mean age, 58.5 years) were recruited through the General Practitioners (GPs) network in France. All had persistent hyperglycemia after a preliminary 3-month period with dietary and life-style modification. Gliclazide (80 to 320 mg/d) was then prescribed as diabetic pharmacotherapy for 2 years. Additional therapy for hypertension and dyslipidemia was started if necessary. The aim of the study was mainly to determine the feasibility of a GP-directed protocol for the monitoring and treatment of newly diagnosed NIDDM patients, and to assess the effectiveness of diabetic therapy in this cohort. Diabetes was diagnosed in 78% of the cohort during routine screening. Among the women, 6.5% had a history of gestational diabetes. Eighteen percent of the patients had a parental history of diabetes, and the dominant maternal role in the genesis of NIDDM was confirmed. High blood pressure (Joint National Committee V criteria) was found at inclusion in 38.8% of the whole cohort. Hyperlipidemia was known in 44.6%. A history of stroke was present in 1.6% of the patients, and coronary heart disease (CHD) in 6.3%. These data support the relationship between the atherogenic state and development of NIDDM. Microalbuminuria defined as urinary albumin excretion (UAE) of at least 20 mg/L was found in 29.6% of the patients, and retinopathy in 9.8%. Among the included patients, 23% did not complete the study and were excluded from the efficacy analysis. Of these, 14% (808 patients) had only baseline evaluation data and 9% (499 patients) withdrew later. Comparison of mean baseline and final results in study completers uncovered a significant improvement in fasting blood glucose ([FBG] 182 +/- 48 v 137 +/- 40 mg/dL), post prandial blood glucose ([PPBG] 209 +/- 68 v 162 +/- 52 mg/dL), and hemoglobin A1c ([HbA1c] 8.7% +/- 2.5% v 7.3% +/- 2.0%). A slight improvement in total cholesterol (228 +/- 44 v 222 +/- 41 mg/dL), body mass index ([BMI] 28.5 +/- 4.7 v 27.9 +/- 4.5 kg/m2), and waist to hip ratio (0.99 +/- 0.1 v 0.98 +/- 0.1) was observed. There was a decrease in the percentage of patients with high blood pressure (38.5% v 30.7%). A mild increase in the prevalence of retinopathy (10.2% v 11.8%) was noted during the study, while the incidence of microalbuminuria remained unchanged (30.2% v 29.5%). In conclusion, the data indicate that the GPs involved in this study were able to successfully monitor and manage NIDDM patients in accordance with a standardized protocol. Gliclazide appeared to be an effective and well-tolerated treatment. The high prevalence of chronic diabetic complications at diagnosis emphasizes the delay encountered in reaching the diagnosis of NIDDM and the problems associated with this delay. In addition to the classic risk factors for NIDDM exhibited in this patient cohort, we have identified CHD and a maternal genetic component as further potential predicting factors.

Aged↗

PubMed1996

[Combined "3-in-1"/sciatic nerve block. Block effectiveness, serum level and side effects using 700 mg mepivacaine 1% without and with adrenaline and prilocaine 1%].

UNLABELLED: A high dose of local anaesthetic is necessary for the combined "3-in-1"/sciatic nerve block. Prilocaine is recommended for its low toxicity. However, in some patients prilocaine results in pronounced methaemoglobin formation due to toludine. Little has been known hitherto about the use of high-dose mepivacaine for the combined 3-1/sciatic nerve block. This study was undertaken to compare the use of 700 mg mepivacaine 1% and of 700 mg prilocaine 1%. METHODS: The study was approved by the ethics committee of our hospital. Once their informed consent had been obtained in writing 3 x 20 patients (ASA 1-2) undergoing planned surgery on the foot or ankle joint were enrolled in the study. The patients were randomized to the following three groups on a double-blind basis: group 1,700 mg mepivacaine without epinephrine; group 2,700 mg mepivacaine with 0.2 mg epinephrine (1:350,000); group 3,700 mg prilocaine 1%. Arterial blood samples for determination of local anaesthetic serum levels were collected over a 120-min period. We determined methaemoglobin and oxygen saturation before and 120 min after the blockade and continued these measurements for 6 h in group 3. At 15-min intervals, all patients were questioned about early signs of toxicity. The perioperative monitoring including blood pressure, ECG and pulse oximetry. Data were analysed using ANOVA and Student's t-test, P < 0.05 considered statistically significant. RESULTS: The blocking efficacy did not differ among the groups (groups 1, 2, 3:90%, 95%, 90%). The maximum mepivacaine serum level in group 1 was 3.91 micrograms/ml +/- 0.95 and 2.94 micrograms/ml +/- 0.58 in group 2 (Fig. 2). Over the entire observation period the addition of epinephrine resulted in a significant reduction of the serum level (between 60.3% at t = 15 min and 19.7% at t = 120 min). In the prilocaine group the maximum serum level was 2.07 micrograms/ml +/- 0.56, significantly less than in either mepivacaine group. No patient showed signs or symptoms of local anaesthetic toxicity. In the prilocaine group there was wide variation in methaemoglobin formation among the patient, with a median of 10.1% (Fig. 3, Table 3). Three patients showed a maximum methaemoglobinemia between 16% and 17%. Five patients were still cyanotic after 6 h when they were transferred to the ward. The fractional SaO2 values amounted to 88% (median) with a minimum of 80.3%. CONCLUSION: Both mepivacaine 1% and prilocaine 1% are appropriate local anaesthetics for the combined 3-in-1/sciatic nerve block at a dose of 700 mg. There was no difference in the blocking efficacy. No patient showed clinical signs or symptoms of a local anaesthetic toxicity. Following prilocaine we are sometimes faced with high methaemoglobinemia, which may necessitate prolonged monitoring.

Adult↗

PubMed1996

Etoposide phosphate infusion with therapeutic drug monitoring in combination with carboplatin dosed by area under the curve: a cancer research campaign phase I/II committee study.

The area under the plasma concentration-time curve (AUC) following an intravenous dose of etoposide varies considerably among patients, which in part contributes to the unpredictability of toxicity and response seen in individual patients. This study evaluated the utility of therapeutic drug monitoring of etoposide in reducing the interpatient variability of etoposide steady-state concentrations during prolonged infusion. The etoposide prodrug etoposide phosphate (Etopophos; Bristol-Myers Squibb Company, Princeton, NJ) was administered by infusion using an adaptive dosing strategy. It was given in combination with carboplatin, which was dosed on an AUC basis. Patients with histologically or cytologically proven small cell lung cancer were treated with etoposide phosphate by continuous 120-hour infusion and carboplatin at a dose calculated by the Calvert formula to give an AUC of 5 mg/ mL.min. Blood samples were taken on days 2 through 5 of each treatment cycle, and high-performance liquid chromatography was used to measure the plasma etoposide concentration. The resultant concentrations were compared with target concentrations of 1 or 2 micrograms/mL and these data were used to calculate the rate of infusion for the following 24 hours. In the first cohort, the target etoposide concentration was 1 microgram/mL, and this was achieved (mean +/- SD = 1.05 +/- 0.24 micrograms/mL) by infusing etoposide phosphate doses of 21 to 109 mg (15 to 68 mg/m2) per day. In the second cohort, the target concentration of 2.0 micrograms/mL was achieved (mean +/- SD = 2.05 +/- 0.31 micrograms/mL) with infused etoposide phosphate doses of 69 to 193 mg (41 to 114 mg/m2) per day. This technique reduced the variation in plasma levels and resulted in predictable hematologic toxicity. Cumulative hematologic toxicity necessitated an extension of the treatment cycle from 3 to 4 weeks, however. Of six evaluable patients, two had a complete response and one had a partial response. Therapeutic drug monitoring was shown to reduce the interpatient variation in the plasma etoposide concentration by half and shows promise for individualizing treatment with combination chemotherapy. Exploiting the known relationships between the pharmacokinetics and pharmacodynamics of these two drugs by using therapeutic drug monitoring may lead to better therapeutic safety and efficacy.

Adult↗

PubMed1997

[Intubation conditions and the development of neuromuscular blockade with rocuronium in endoscopic ORL surgery].

UNLABELLED: Rocuronium is a new nondepolarizing muscle relaxant for which a fast onset has been described. The goal of this study was to examine whether the characteristics of rocuronium could make it an appropriate relaxant for the anaesthetic management of operations of intermediate duration such as endoscopic upper airway surgery. These operations, which require the anaesthesiologist and surgeon to "share" the patient's airway, require good muscle relaxation for endotracheal intubation and placement of endoscopic instruments. In addition, the time course of neuromuscular blockade and its relation to the quality of intubating conditions were analysed. METHODS: The study was approved by the local ethics committee; 30 patients (ASA status 1-3) scheduled for elective endoscopic upper airway surgery were included after written informed consent. Exclusion criteria were suspected difficult intubating conditions, neuromuscular disease, or antibiotic therapy with aminoglycosides during the last 24 h. Anaesthesia was induced by propofol 2 mg/kg and alfentanil 1 mg after volume loading with 500 ml Ringer's lactate and preoxygenation, and was maintained by propofol infusion 5-8 mg/kg/h and repetitive alfentanil injections according to clinical needs. Endotracheal intubation was performed by a senior anaesthesiologist 90 s after injection of rocuronium 0.6 mg/kg (2 x ED95). Intubating conditions were graded 1 to 4 (1 = excellent, 2 = good, 3 = sufficient, 4 = inadequate). Acceleromyography was used for neuromuscular monitoring by means of the TOF-guard (organon Teknika/Biometer). The adduction movement of the thumb was measured by an acceleration transducer while stimulating the ulnar nerve at the wrist via surface electrodes in a supramaximal train-of-four (TOF) mode (2 Hz every 15 s). Twitch height and TOF ratio were documented during the course of neuromuscular blockade. Data are presented as mean +/- standard deviation. RESULTS: Patients were aged 37 to 64 years (mean 54 +/- 7). Intubating conditions were excellent in 17 cases and good in 7. In 2 cases intubating conditions were graded sufficient, as patients could be easily intubated but showed clear diaphragmatic movements at intubation. In 4 patients intubating conditions could not be judged, as a laryngoscopic view of the glottic structures was impossible for anatomic reasons. Neuromuscular block at intubation was 78 +/- 22%, onset time 152 +/- 62 s, clinical duration 30 +/- 8 min, and recovery index 11 +/- 4 min. The TOF ratio required 51 +/- 14 min to return to 0.7. CONCLUSIONS: Good to excellent intubating conditions can be expected 90 s after injection of rocuronium 0.6 mg/kg. Diaphragmatic reactions cannot be excluded. Complete relaxation of the adductor pollicis muscle is not necessary for endotracheal intubation. Intubation at a certain time interval, for example, 90 s after injection of rocuronium 0.6 mg/kg, can be recommended. Onset and recovery characteristics of rocuronium make it an appropriate relaxant for the anaesthetic management of operations of intermediate duration such as endoscopic upper airway surgery. Care should be given, however, to detect inadequate recovery of neuromuscular transmission, as there are considerable interindividual differences in recovery.

Adult↗

PubMed2002

American Society of Clinical Oncology clinical practice guidelines: the role of bisphosphonates in multiple myeloma.

PURPOSE: To determine clinical practice guidelines for the use of bisphosphonates in the prevention and treatment of lytic bone disease in multiple myeloma and to determine their respective role relative to other conventional therapies for this condition. METHODS: An expert multidisciplinary Panel reviewed pertinent information from the published literature through January 2002. Values for levels of evidence and grade of recommendation were assigned by expert reviewers and approved by the Panel. Expert consensus was used if there were insufficient published data. The Panel addressed which patients to treat and when to treat them in the course of their disease. Additionally, specific drug delivery issues, duration of therapy, initiation of treatment and management of treatment of lytic bone disease was reviewed and compared with other forms of therapy for lytic bone lesions. Finally, the Panel discussed patient and physician expectations associated with this therapy for bony metastases, as well as public policy implications related to the use of bisphosphonates. The guidelines underwent external review by selected physicians, by the Health Services Research Committee members, and by the ASCO Board of Directors. RESULTS: The available evidence involving randomized controlled trials is modest but supports that oral clodronate, intravenous pamidronate, and intravenous zoledronic acid are superior to placebo in reducing skeletal complications. A reduction in vertebral fractures has consistently been seen across all studies. No agent has shown a definitive survival benefit. Intravenous zoledronic acid has recently been shown to be as effective as intravenous pamidronate. Because there are no direct comparisons between clodronate and pamidronate or zoledronic acid, the superiority of one agent cannot be definitively established. However, the panel recommends only intravenous pamidronate or zoledronic acid in light of the use of the time to first skeletal event as the primary end point and more complete assessment of bony complications in studies evaluating it. Additionally, clodronate is not available in the United States. The choice between pamidronate and zoledronic acid will depend on choosing between the higher drug cost of zoledronic acid, with its shorter, more convenient infusion time (15 minutes), versus the less expensive drug, pamidronate, with its longer infusion time (2 hours). CONCLUSION: Bisphosphonates provide a meaningful supportive benefit to multiple myeloma patients with lytic bone disease. However, further research on bisphosphonates is warranted, including the following: (1) when to start and stop therapy, (2) how to integrate their use with other treatments for lytic bone disease, (3) how to evaluate their role in myeloma patients without lytic bone involvement, (4) how to distinguish between symptomatic and asymptomatic bony events, and (5) how to better determine their cost-benefit consequence.

Clodronic Acid↗

PubMed1999

[Propofol for intubation of infants after halothane induction].

UNLABELLED: The unwanted side effects of muscle relaxants used for anaesthesia in the newborn and infants resulted in a search for alternatives to atraumatic intubation (IN). The study was aimed to investigate conditions of intubation, time of intubation as well as changes in systolic, mean and diastolic blood pressure (RRs/RRm/RRd) and heart rate (HR) under the use of propofol (P) after narcosis induction by mask. PATIENTS AND METHODS: The study was approved by the local ethics committee. The data was analysed from 100 infants aged between 4 days and 56 weeks (weight 2110-9230 g) in the ASA I and II groups (Group [Gr] A and B both with 50 patients). In both groups induction was performed inhalationally with halothane (1.5-2.0 vol%) and pure oxygen. After that propofol for intubation was applied in a dose of 2 mg/kg i.v. In Gr A blood pressure and heart rate were registered at three measuring points (MP): MP 1 = before P administration, MP 2 = after P, MP 3 = following intubation; in Gr B at MP 1 and MP 3. Additionally in Gr B the intubation time was recorded in seconds (t1 = time after P administration to beginning of IN, t2 = time after P administration to the end of the IN, t3 = t2-t1). In both groups the conditions of intubation were assessed (score 1--excellent, 2--good, 3--bad, 4--impossible intubation). RESULTS: The means of RRs/RRm/RRd/HR varied in Gr A at MP 2 by -11.20*/-9.18*/-8.58*/-3.52 mmHg/bpm and at MP 3 by -2.74/-2.26/-2.04/+5.46 mmHg/bpm in comparison to MP 1 (p < 0.05 = significant*). Compared to MP 1 in Gr B the mean values of RRs/RRm/RRd/HR varied at MP 3 by -0.89/+0.50/-0.80/+4.20* mmHg/bpm. T1 (mean, SD) was 10.88 +/- 3.52 seconds (s), t2 26.22 +/- 6.12 s, and t3 was therefore 15.78 +/- 6.28 s. Conditions of intubation were found to be excellent or good in both groups (Gr A and B [100 patients]: score 1 = 95x = 95%, score 2 = 5x = 5%). CONCLUSION: In the observation period, changes in heart rate stayed in the range of reference. In our opinion the excellent and good conditions for intubation, as well as the ultrashort drug-onset and intubation time demonstrate the good characteristics afforded by propofol to perform intubation in infancy.

Anesthesia, General↗

PubMed2003

Surveillance for safety after immunization: Vaccine Adverse Event Reporting System (VAERS)--United States, 1991-2001.

PROBLEM/CONDITION: Vaccines are usually administered to healthy persons who have substantial expectations for the safety of the vaccines. Adverse events after vaccinations occur but are generally rare. Some adverse events are unlikely to be detected in prelicensure clinical trials because of their low frequency, the limited numbers of enrolled subjects, and other study limitations. Therefore, postmarketing monitoring of adverse events after vaccinations is essential. The cornerstone of monitoring safety is review and analysis of spontaneously reported adverse events. REPORTING PERIOD COVERED: This report summarizes the adverse events reported to the Vaccine Adverse Event Reporting System (VAERS) from January 1, 1991, through December 31, 2001. DESCRIPTION OF SYSTEMS: VAERS was established in 1990 under the joint administration of CDC and the Food and Drug Administration (FDA) to accept reports of suspected adverse events after administration of any vaccine licensed in the United States. VAERS is a passive surveillance system: reports of events are voluntarily submitted by those who experience them, their caregivers, or others. Passive surveillance systems (e.g., VAERS) are subject to multiple limitations, including underreporting, reporting of temporal associations or unconfirmed diagnoses, and lack of denominator data and unbiased comparison groups. Because of these limitations, determining causal associations between vaccines and adverse events from VAERS reports is usually not possible. Vaccine safety concerns identified through adverse event monitoring nearly always require confirmation using an epidemiologic or other (e.g., laboratory) study. Reports may be submitted by anyone suspecting that an adverse event might have been caused by vaccination and are usually submitted by mail or fax. A web-based electronic reporting system has recently become available. Information from the reports is entered into the VAERS database, and new reports are analyzed weekly. VAERS data stripped of personal identifiers can be reviewed by the public by accessing http://www.vaers.org. The objectives of VAERS are to 1) detect new, unusual, or rare vaccine adverse events; 2) monitor increases in known adverse events; 3) determine patient risk factors for particular types of adverse events; 4) identify vaccine lots with increased numbers or types of reported adverse events; and 5) assess the safety of newly licensed vaccines. RESULTS: During 1991-2001, VAERS received 128,717 reports, whereas >1.9 billion net doses of human vaccines were distributed. The overall dose-based reporting rate for the 27 frequently reported vaccine types was 11.4 reports per 100,000 net doses distributed. The proportions of reports in the age groups <1 year, 1-6 years, 7-17 years, 18-64 years, and >/= years were 18.1%, 26.7%, 8.0%, 32.6%, and 4.9%, respectively. In all of the adult age groups, a predominance among the number of women reporting was observed, but the difference in sex was minimal among children. Overall, the most commonly reported adverse event was fever, which appeared in 25.8% of all reports, followed by injection-site hypersensitivity (15.8%), rash (unspecified) (11.0%), injection-site edema (10.8%), and vasodilatation (10.8%). A total of 14.2% of all reports described serious adverse events, which by regulatory definition include death, life-threatening illness, hospitalization or prolongation of hospitalization, or permanent disability. Examples of the uses of VAERS data for vaccine safety surveillance are included in this report. INTERPRETATION: As a national public health surveillance system, VAERS is a key component in ensuring the safety of vaccines. VAERS data are used by CDC, FDA, and other organizations to monitor and study vaccine safety. CDC and FDA use VAERS data to respond to public inquiries regarding vaccine safety, and both organizations have published and presented vaccine safety studies based on VAERS data. VAERS data are also used by the Advisory Committee on Immunization Practices and the Vaccine and Related Biological Products Advisory Committee to evaluate possible adverse events after vaccinations and to develop recommendations for precautions and contraindications to vaccinations. Reviews of VAERS reports and the studies based on VAERS reports during 1991-2001 have demonstrated that vaccines are usually safe and that serious adverse events occur but are rare. PUBLIC HEALTH ACTIONS: Through continued reporting of adverse events after vaccination to VAERS by health-care providers, public health professionals, and the public and monitoring of reported events by the VAERS working group, the public health system will continue to be able to detect rare but potentially serious consequences of vaccination. This knowledge facilitates improvement in the safety of vaccines and the vaccination process.

Adolescent↗

PubMed1999

[Postoperative nausea and vomiting following stabismus surgery in children. Inhalation anesthesia with sevoflurane-nitrous oxide in comparison with intravenous anesthesia with propofol-remifentanil].

BACKGROUND: Postoperative nausea and vomiting (PONV) is still one of the major problems in strabismus surgery, especially in children. In recent years many studies have been published, suggesting that choosing propofol as the anaesthetic agent may help to reduce the high incidence of PONV in children undergoing strabismus surgery. Experience with remifentanil in children is still very limited and little is known, whether propofol in combination with this new short acting opioid is also superior regarding PONV in squint surgery compared to sevoflurane/N2O. Additionally, little is known, whether the type of operation or the muscle which is operated on has any influence with respect to PONV. METHODS: Following sample size estimation, ethics committee approval and parents informed consent in a prospective, randomised, observer-blind study 105 ASA I and II children aged 3-8 years scheduled for elective strabismus surgery were assigned into one of the following groups: Group TIVA (propofol/remifentanil, n = 53): anaesthesia was induced by remifentanil 0.5 microgram kg-1 min-1 over 2 min (loading phase), followed by 3 mg kg-1 propofol along with 30% O2 in air. After endotracheal intubation anaesthesia was maintained initially with remifentanil 0.25 microgram kg-1 min-1 and propofol 10 mg kg-1 h-1 by constant infusion. In the course of the operation the infusions of the anaesthetics were adjusted to the decreasing need for anaesthesia. Group VOLATIL (sevoflurane/N2O, n = 52): anaesthesia was induced by inhalation of sevoflurane along with 50% O2 in N2O. After endotracheal intubation anaesthesia was maintained with sevoflurane 1.0-1.5 MAC along with 30% O2 in N2O and in the course of the operation the administration of the inhaled anaesthetics was adjusted correspondingly. Preoperatively collected data included gender, age, weight and history of PONV. Intraoperatively collected data consisted of data belonging to routine monitoring (heart rate, blood pressure, peripheral oxygen saturation and temperature) as well as the duration of the operation and anaesthesia and specific data regarding the operation (including the number and type of muscles as well as the kind of operation). Data collected within the first 24 hours postoperatively in the recovery room and on the ward by blinded observers included any PONV events as well as the antiemetics and analgesics applied. RESULTS: Vomiting was observed less frequently in the TIVA-group than in the VOLATIL-group (21 of 53 vs. 32 of 52, p = 0.03) within the first 24 hours postoperatively. Posterior fixation suture ("faden-operation") compared to other operations was followed rather frequently by nausea and vomiting (30 of 44 and 33 of 44, respectively), whereas recessions were rarely associated with nausea and vomiting (12 of 35 and 9 of 35, respectively). CONCLUSIONS: TIVA with propofol/remifentanil proved to be a suitable form of anaesthesia for children in this setting. Propofol showed advantages over sevoflurane/N2O with respect to PONV after squint surgery in children also when applied in the combination with remifentanil. TIVA with propofol/remifentanil may therefore be one way to reduce the high incidence of PONV in this setting, bearing in mind, that PONV is not only influenced by the regimen of the general anaesthesia but rather by the combination of many other factors, in particular the type of operation.

Anesthesia, Inhalation↗

PubMedDate not supplied

Vertical evacuation simulation of critically ill patients in a hospital.

INTRODUCTION: The world's new social environment dictates the need for preparedness should a disaster occur. One caveat in the realm of disaster preparedness is the vertical evacuation of hospital patients. Little data regarding the evacuation of patients are available, and the consequences of not being prepared could be devastating. Therefore, if the vertical evacuation of critically ill patients was thrust upon a community hospital, the response of emergency services and ancillary staff is largely unknown. METHODS: The vertical evacuation of 12 simulated critically ill patients from the fourth floor of a newly constructed and vacant critical care unit was undertaken by local fire fighters, on-staff nursing, residents, and ancillary staff, all under the direction of the hospital Emergency Management Committee. Four randomly selected groups of firefighters, two teams consisting of three personnel and two teams of four personnel, were timed and had vital signs assessed prior to ascending to the fourth floor to retrieve a patient and upon each subsequent decent. Each team, dressed in full turnout gear, retrieved three patients. Each simulated patient was fashioned with mock endotracheal tube, intravenous lines, monitor, and a Pleurovac was attached in three of the four patients. Vital signs were analyzed for significant changes or patterns due to exertion and or stress during the drill. Evaluations were distributed to all participants upon completion of the drill. RESULTS: Mean values for the vital signs of the members of each team showed minimal increases from baseline to completion with the exception of heart rate. A decrease in systolic blood pressure was present in both of the four member teams. Subjective evaluation by the firefighters, indicated a "minimal" increase in exertion. Mean extraction time was 14.7 minutes. Patient transfer and evacuation was completed without complication to the patients or staff. Only one firefighter requested a replacement. Completed evaluations indicated above average or outstanding performance on organization, commitment, security, and care. Comments included statements regarding equipment management during transport, better communication, stairwell width, difficulty with ventilating intubated patients, improvement of evacuation time, and organization as drill progressed; three member teams, spatially, worked better than four. CONCLUSION: This drill reflected an impressive level of preparedness by firefighters, nurses, and ancillary staff both physically and organizationally. Should a vertical evacuation of critically ill patients be necessary, a four firefighter extraction team and accompanying nurse and respiratory therapist would be able to evacuate one patient at a rate of 3.75 minutes per floor.

Critical Illness↗

PubMed1997

[Intraoperative pain stimuli change somatosensory evoked potentials, but not auditory evoked potentials during isoflurane/nitrous oxide anesthesia].

PURPOSE: Evoked potentials are used for intraoperative monitoring to assess changes of cerebral function. This prospective randomised study assesses the influence of surgical stimulation on midlatency components of somatosensory (SEPs) and auditory evoked potentials (AEPs) in anaesthetised patients. METHODS: After approval of the Ethics Committee and written informed consent 36 orthopaedic patients (34 +/- 15 y, 73 +/- 14 kg. 1.71 +/- 0.07 m, ASA I-II) were randomly included in the study. Anaesthesia was induced with 1.5 micrograms/kg fentanyl, 0.3 mg/kg etomidate and 0.1 mg/kg vecuronium. The lungs were intubated and patients normoventilated in steady state anaesthesia with isoflurane (end-tidal 0.6%) and 66% nitrous oxide. 18 patients (group 1) were assigned to the SEP group: median nerve stimulation, recording at Erb, C 6 and the contralateral somatosensory cortex (N20, P25, N35) vs Fz. AEPs were recorded in group 2 (n = 18): binaural stimulation, recording at Cz versus linked mastoid (V, Na, Pa, Nb). Recordings were performed during 30 min before the start of surgery (baseline: BL), at skin incision (SURG1) and at the preparation of the periost (SURG2). Heart rate, mean arterial blood pressure, oxygen saturation, endtidal pCO2 and isoflurane (PetISO) concentrations were registered simultaneously. Data were analysed by one-way analysis of variance. Post hoc comparison were made by Mann-Whitney U-Wilcoxon Rank Sum Test with p < 0.05 significant. RESULTS AND DISCUSSION: During steady state isoflurane anaesthesia surgical stimulation (SURG2) resulted in significant increases of N20 P25 amplitudes compared with BL (BL: 1.4 +/- 0.7 microV; SURG2: 2.0 +/- 0.8 microV; p < 0.05). Latencies of SEPs and midlatency components of AEPs did not change over time. There were no differences in autonomic parameters between SEP and AEP groups. MAP increased from 76 +/- 6 mmHg at BL to 93 +/- 16 mmHg at SURG1 and 96 +/- 17 mmHg at SURG2 (n = 36; p < 0.05). HR increased from BL (60 +/- 8 beats/min) to SURG2 (76 +/- 12 beats/min). Increases of amplitudes of midlatency SEP amplitudes indicate increased nociceptive signal transmission which is not blunted by isoflurane-nitrous oxide anaesthesia. In contrast, unchanged AEPs indicate adequate levels of the hypnotic components of anaesthesia.

Adult↗

PubMed1998

Perioperative tissue thickness measurement by a new miniature ultrasound device.

INTRODUCTION: A recently developed mini ultrasound device for measurement of peripheral tissue thickness is now available for use in clinical practice. Whether this device allows a better guidance of perioperative fluid therapy has to be investigated. Therefore, it is necessary to get basic data on the parameter tissue thickness in otherwise healthy patients during surgery. The aim of the present study was to evaluate differences in tissue thickness change between patients in supine and head down position with a novel handheld ultrasound device during the perioperative course of healthy surgical patients under a standardized fluid regimen. METHODS: After obtaining ethics committee approval and informed consent we studied 19 ASA 1-2 female patients undergoing gynecological procedures in supine (SUP, n = 11) or in 30 degrees head down position (HD, n = 8) in general anesthesia. Preoperative NPO status was comparable in both groups. Lactated Ringer's solution (LR) was continuously infused at a rate of 8 ml/kg b.w./h over 90 min and tissue thickness (TT) was determined by ultrasound before induction (t0) and in 30 min intervals (t30, t60, t90) at the forehead. Simultaneously plasma viscosity (PV) was evaluated. RESULTS: Group SUP presented at t0 a forehead TT of 5.3 mm (SD +/- 0.5), at t30 TT was unchanged. At t60 mean TT increased significantly to 5.6 mm, (+/- 0.6). At t90 mean TT remained stable at 5.7 mm (+/- 0.5). Group HD presented at t0 a mean TT of 4.6 mm (+/- 0.7), at t30 mean TT was 4.9 mm (+/- 0.7) and at t60 mean TT of the forehead skin was measured as 5.3 mm (+/- 0.6). Significance to t0 was reached at t90 with a mean TT of 5.4 mm (+/- 0.7). Group HD showed a steeper increase and a parallel stabilization phase at the end. Differences between t0 and t90 have been significant. Mean PV in the SUP group at t0 (1.361 mPa*s, SD: +/- 0.045) decreased under the infusion therapy to 1.276 mPa*s (+/- 0.04) at t90. Mean PV in the HD group was determined 1.351 mPa*s (+/- 0.06) at t0 and declined to 1.274 mPa*s (+/- 0.03) at t90. CONCLUSIONS: The findings suggest that fluid replacement after an NPO period and the expected changes of forehead TT due to positioning of the patient are detectable by this new ultrasound device.

Adult↗

PubMed2000

[The practicability, patient comfort and efficiency of the pre-oxygenation device NasOral].

OBJECTIVE: We examined the new NasOral-System (NOS; Logomed, Germany), which is designed for a fasten and more complete denitrogenization when compared to the use of a contemporary face-mask. The patient inhales oxygen via a nose mask and exhales via mouthpiece. Nose mask and mouthpiece have built-in one-way valves, resulting in an unidirectional gas flow (nasal-oral). METHODS: With approval of the local ethic committee, pre-oxygenation with both the NOS and a face mask (Laerdal) was studied in 50 adult patients. Midazolam 3.75-7.5 mg p.os was given for premedication. The NOS was studied in two different ways: the nose mask fastened by rubberband and with the nose mask held by hand. Prior to induction every patient received every system in a randomised manner. Semi-closed-anaesthetic circle-systems with a fresh-gas-flow of 10 litres/min were used. The FEO2 over 5 min of pre-oxygenation were recorded (AS-3, Datex). Speed and degree of the denitrogenization was documented by an external digital data-acquisition system. Practicability of the systems regarding the anaesthesists (n = 27) and patient comfort were evaluated by means of a standardized postoperative questionnaire. RESULTS: The hand-held NOS is definitely more effective and reliable than both the NOS fastened by rubber-band and the classical face mask: 80% of the hand-held NOS were able to achieve a FEO2 of > or = 0.8 compared to only 36% of the NOS fixed by rubber-band, face mask: 48%. FEO2 of > or = 0.8 was achieved with 52% of the hand-held NOS in 90 s, a time we consider practical for daily routine, whereas only 10% of the NOS fixed by rubberband and 14% of the face masks accomplished this threshold. A cooperative patient is an important condition when using the NOS: a strong premedication effect, absence of dentures, and patients who can not inspire via nose and expire via mouth involve impairment of the positive effects of the NOS. 21% of the anaesthesists felt disturbed by the NOS. 72% do not believe, that induction of anaesthesia will become more safe with the NOS. For 8 patients, breathing with the NOS was disagreeable (face-mask: 3 patients), 15 were disturbed by the nose part/mouth piece (face-mask: no patient). CONCLUSION: An acceptable FEO2 of > or = 0.8 can be achieved only without leakage of both the NOS and the face-mask. Therefore, routine FEO2-monitoring seems highly desirable. Efficiency of the hand-held NOS is much better than with the NOS fastened by rubberband or the face mask. However, even the hand-held NOS cannot guarantee for optimal denitrogenization. Practicability in daily use was poor, because a test of airway patency by manual ventilation prior to relaxation/intubation is not possible with the NOS. Using the device as a help in apnoic oxygenation seems useful.

Adult↗

PubMed1994

[Effect of capnoperitoneum on postoperative carbon dioxide homeostasis].

After laparoscopic cholecystectomy, carbon dioxide (CO2) must be exhaled after resorption from the abdominal cavity. There is controversy about the amount and relevance of postoperative CO2 resorption. Without continuous postoperative monitoring, after laparoscopic cholecystectomy a certain risk may consist in unnoticed hypercapnia due to CO2 resorption. Studies exist on the course of end-expiratory CO2 (Pe-CO2) alone over a longer postoperative period of time in extubated patients during spontaneous breathing. The goal of this prospective study was to investigate the amount of CO2 resorbed from the abdominal cavity in the postoperative period by means of CO2 metabolism. METHODS. After giving informed consent to the study, which was approved by the local ethics committee, 20 patients underwent laparoscopic cholecystectomy. All patients received general endotracheal anaesthesia. After induction, total IV anaesthesia was maintained using fentanyl, propofol, and atracurium. Patients were ventilated with oxygen in air (FiO2 0.4). The intra-abdominal pressure during the surgical procedure ranged from 12 to 14 mm Hg. Thirty minutes after releasing the capnoperitoneum (KP), CO2 elimination (VCO2), oxygen uptake (VO2), and respiratory quotient (RQ) were measured every minute for 1 h by indirect calorimetry using the metabolic monitor Deltatrac according to the principle of Canopy. Assuming an unchanged metabolism, the CO2 resorption (delta VCO2) at any given time (t) can be calculated from delta VCO2 (t) = VCO2 (t)-RQ(preop) VO2 (t). It was thus necessary to define the patient's metabolism on the day of operation. The first data were collected before surgery and after introduction of the arterial and venous cannulae for a 15-min period. Measuring point 0 was determined after exsufflation of the KP and emptying of the remaining CO2 via manual compression by the surgeon at the end of surgery. Patient's tracheas were extubated and metabolic monitoring started 30 min after release of the KP for 60 min. Simultaneously, a nasal side-stream capnometry probe was placed and the PeCO2 and respiratory frequency (RF) were obtained by the Capnomac Ultima (Datex) and registered every minute as well. Values were averaged over four periods of 15 min each. An arterial blood gas sample was drawn at the end of every 15-min period. Postoperative pain was scored by a visual analog scale and completed by a subjective index questionnaire on general well-being. All data were analysed by the Friedman or Wilcoxon test; P < 0.05 was considered significant. RESULTS. The findings do not indicate CO2 resorption in the postoperative period after laparoscopic cholecystectomy (Tables 2 and 3, Fig. 1). Arterial CO2 as well as PeCO2 were elevated postoperatively (45 mm Hg vs. 36 mm Hg intraoperatively), while VCO2 and VO2 were unchanged when compared to the preoperative measuring period. The postoperative RF was comparable to preoperative values. Calculated delta CO2 was lower than 10 ml/min and within accuracy of measurements. The post-operative pain index ranged between 3 and 4, and 3.75-15 mg piritramid was administered. All patients felt tired immediately after the operation, but scores improved slightly at the end of the 60-min period of metabolic monitoring. CONCLUSIONS. There is no significant resorption of CO2 from the abdominal cavity later than 30 min after releasing the KP. Up to this time, any CO2 remaining in the abdominal cavity after careful emptying by the surgeon has been resorbed and exhaled. An increased PeCO2 as late as 30 to 90 min postoperatively should rather be considered a consequence of residual anaesthetics and narcotics than of CO2 resorption.

Adult↗

PubMed1996

[A comparative study of intravenous opioid analgesia. Sufentanil and alfentanil for extracorporeal shock-wave lithotripsy in urologic patients].

UNLABELLED: Extracorporeal shock-wave lithotripsy (ESWL) is the method of choice for the treatment of solitary stones in the kidney or ureter. Early lithotripters required prolonged immobility of the patient and caused considerable pain, necessitating general or epidural anaesthesia during the procedure. Modern lithotripters are quicker, but still require analgesia. Intravenous opioids are currently the drugs in favour. The opioids most commonly used are fentanyl and its shorter-acting analogue, alfentanil. The latter has a more rapid onset and, because of its reduced lipid solubility, is less cumulative. Sufentanil is a new opioid that is also of the phenylpiperidone group and has been recently licensed and introduced in Germany. Its pharmacokinetic and pharmacodynamic properties suggest an intermediate duration of action, high analgesic potency, and cardiovascular stability with diminished respiratory depression. In this prospective double-blind study, the effects of alfentanil and sufentanil on cardiovascular and respiratory parameters, the quality of analgesia, degree of sedation and the number and type of side-effects were compared. PATIENTS AND METHODS: After giving informed consent and with the approval of the hospital ethics committee, 62 patients (ASA I or II) were investigated. They were randomly allocated to two groups, either receiving sufentanil (n = 32) or alfentanil (n = 30) during ESWL. No premedication was given. Excluded were patients with pain prior to treatment, patients treated with a spasmolytic or analgesic drug and those who had undergone ESWL within the last 6 months. The loading dose was given as a 5-min infusion to each group. The heart rate, systolic and diastolic blood pressure, percutaneous oxygen saturation (SpO2), and the transcutaneous capillary carbon dioxide tension (PicCO2) were recorded prior to the procedure (i.e. before administration of opioid), after 1000 and after 2000 shock waves and then 1 and 2 h after the end of lithotripsy. After 1000 and 2000 shock waves, and 1 an 2 h after the treatment, the patients were asked to express their degree of tiredness and pain on a visual analogue scale (VAS). The occurrence of side-effects such as nausea, vomiting, pruritus or other unpleasant sensations were noted by an anaesthesia nurse. Simultaneously, the anaesthetist recorded his/her impression of the patient's tiredness and degree of pain, both by using the VAS. He was not allowed to question the patient, nor was he aware of the patient's own scores. At the end of the observation period both the patient and the anaesthetist related their overall satisfaction with the anaesthetic procedure, again by using the VAS. Data were analysed with the Mann-Whitney-U for comparisons between groups and with the Wilcoxon test within each group. The side-effects were analysed with the Chi-square test. RESULTS: The systolic and diastolic blood pressure remained stable in both groups during and after treatment. The mean heart rate was different between the two groups at the beginning, and after the end of the treatment it dropped in both groups, but no significant difference was seen between groups. The PicCO2 rose from an initial mean of 36.8 mm Hg to a maximum of 44.6 mm Hg after 1000 shock waves in the sufentanil group, and from 37.8 mm Hg to 46.0 mm Hg after 2000 shock waves in the alfentanil group. The differences were significant within groups until 1 h after the end of the treatment, but there was no significant difference between groups. The oxygen saturation SpO2 dropped slightly in both groups. The differences were not significant between groups. In the alfentanil group, one patient had a maximum carbon dioxide tension of 83 mm Hg after 2000 shock waves, whereas in the sufentanil treated group the oxygen saturation fell to 72% in one case. (ABSTRACT TRUNCATED)

Alfentanil↗