Predicting Plasma Olanzapine Concentration Following a Change in Dosage: A Population Pharmacokinetic Study.

INTRODUCTION: Due to high inter-individual variability in peripheral pharmacokinetic parameters, dosing of antipsychotics currently relies on clinical trial-and-error, and predicting antipsychotic plasma concentrations before changing a dose has been a challenge. METHODS: Patients with schizophrenia receiving a stable dose of olanzapine were included. 2 plasma samples were collected at 2 given time points for the measurement of plasma olanzapine concentrations. At least 7 days after a dosage change of olanzapine, a third sample was collected. The plasma concentration of the third sample was predicted in a blinded fashion using a mixed-effects model with NONMEM(®), using the following information: the 2 baseline plasma concentrations, the interval between the last dose and blood draw, and clinical and demographic information. RESULTS: 31 subjects (mean±SD age=56.0±11.6; 19 men) were enrolled. The mean prediction (95% confidence interval) errors were 1.6 (-2.8 to 6.0) ng/mL. A highly significant correlation was observed between the observed and predicted concentrations of the third sample (r=0.91, p<0.001). DISCUSSION: Plasma olanzapine concentrations following an actual dosage change can be predicted in advance with a high degree of certainty.

Percutaneous tracheostomy, a systematic review.

BACKGROUND: Percutaneous dilatational tracheostomy (PDT) is a common procedure in intensive care units and the identification of the best technique is very important. We performed a systematic review and meta-analysis of randomized studies comparing different PDT techniques in critically ill adult patients to investigate if one technique is superior to the others with regard to major and minor intraprocedural complications. METHODS: BioMedCentral and other database of clinical trials were searched for pertinent studies. Inclusion criterion was random allocation to at least two PDT techniques. Exclusion criteria were duplicate publications, nonadult studies, and absence of outcome data. STUDY DESIGN: Population, clinical setting, and complications were extracted. RESULTS: Data from 1130 patients in 13 randomized trials were analyzed. Multiple dilators, single-step dilatation, guide wire dilating forceps, rotational dilation, retrograde tracheostomy, and balloon dilation techniques were always performed in the intensive care unit. The different techniques and devices appeared largely equivalent, with the exception of retrograde tracheostomy, which was associated with more severe complications and more frequent need of conversion to other techniques when compared with guide wire dilating forceps and single-step dilatation techniques. Single-step dilatation technique was associated with fewer failures than rotational dilation, and fewer mild complications in comparison with balloon dilation and guide wire dilating forceps (all P < 0.05). CONCLUSIONS: Among the six analyzed techniques, single-step dilatation technique appeared the most reliable in terms of safety and success rate. However, the number of available randomized trials was insufficient to confidently assess the best PDT technique.

Predicting age-specific dosing of antipsychotics.

Antipsychotic medications are the standard of care for both acute and maintenance treatment of schizophrenia, the latter requiring an indefinite treatment across a patient's life span. However, dosing and tolerability of antipsychotics have been studied primarily in younger patients, and very limited data are available for age- and phase-specific dosing. This leaves the clinician with no guidance on dose adjustment as patients grow older-an issue of critical importance, especially in light of recent concerns about increased morbidity and mortality associated with antipsychotics.

Activities of a medical emergency team twenty years after its introduction.

INTRODUCTION: We describe and quantify the wide range of activities that a mature Medical Emergency Team can progressively perform. METHODS: The activities performed by a Medical Emergency Team 20 years after its introduction were prospectively collected during 105 consecutive days. RESULTS: The main activity was focused on the follow-up visits to previously treated critically ill patients (mean 7.5 visits/die in working days, 5.1 in the others). A large amount of other scheduled or unscheduled activities (like sedation or analgesia for diagnostic procedures, central venous line placement, phone consultation regarding critical care aspects of treatments) were performed: on average, 7.3 side-activities/die in working days and 5.2 in the others. First consultations in patients not previously seen were on average 3.1/die on working days, 2.4 in the others. Cardiac arrest accounted for 27 (9%) of first time visits. CONCLUSIONS: A Medical Emergency Team can progressively perform many kinds of activities. An evaluation limited to the reduction of in-hospital cardiac arrests or a too early assessment may underestimate its beneficial effects on the Hospital complexity.

Dilatative percutaneous tracheostomy during double antiplatelet therapy: two consecutive cases.

This article reports two cases of dilatative percutaneous tracheostomy performed on patients treated with double antiplatelet therapy. Both patients had cardiac arrest following myocardial infarction. After primary angioplasty with stent placement, a double antiplatelet therapy was started. Due to poor neurological outcome, dilatative percutaneous tracheostomy was performed on both patients. Antiplatelet therapy was not discontinued because of the unacceptable risk of stent thrombosis. No immediate or late hemorrhagic complications occurred. In our experience, dilatative percutaneous tracheostomy during double antiplatelet therapy can be safely performed in selected patients without other risk factors.

Low perioperative mortality for cardiac surgery in octogenarians.

AIM: The number of cardiac operations in octogenarians is steadily increasing. A review of personal 4 years' experience is made in order to identify which variables are associated to a poor prognosis in this high risk population. METHODS: Perioperative variables and short-term outcome of 109 consecutive octogenarians were prospectively collected in a database. Data were analysed with descriptive statistics. Univariate and multivariate analyses were performed to identify preoperative risk factors for prolonged mechanical ventilation and ICU stay. RESULTS: The 109 octogenarians represented 1.8% of the 4 940 cardiac operations performed at our University Teaching Hospital in the period January 1998-June 2001: 94 patients had comorbidities (86%); 46 underwent valve surgery (42%), 38 had coronary artery bypass grafting surgery (36%), and combined procedures or aortic arch replacement were performed in 25 patients (22%). Two patients died (1.8%). Postoperative complications included: myocardial infarction (10 patients, 9%), stroke (6 patients, 5%), renal replacement therapy (1 patient, 1%). Sixty nine patients (63%) had an uneventful perioperative period (63%). On a multivariate analysis, cardiopulmonary bypass (CPB) time was associated with prolonged intubation and ICU stay; mitral pathology predicted prolonged intubation while previous cardiac surgery was associated with prolonged ICU stay. CONCLUSION: The 109 octogenarians studied had an excellent course in the immediate postoperative period. Therefore, on the basis of personal experience cardiac surgery could be safely performed in octogenarians.

Prilocaine or mepivacaine for combined sciatic-femoral nerve block in patients receiving elective knee arthroscopy.

AIM: The aim of this study was to evaluate the onset time of surgical block, recovery of motor function and duration of post-operative analgesia of combined sciatic-femoral nerve block performed with either mepivacaine or prilocaine. METHODS: With Ethical Committee approval and written informed consent, 30 ASA physical status I-II patients, undergoing elective arthroscopic knee surgery, received a combined sciatic-femoral nerve block with 30 ml of either 2% mepivacaine (n=15) or 1% prilocaine (n=15). An independent observer recorded the onset time of sensory and motor blocks, the need for intraoperative analgesia supplementation, recovery of motor function, and first request of post-operative pain medication. RESULTS: Onset time of nerve block required 15+/-5 min with prilocaine and 12+/-7 min with mepivacaine (p=0.33). No patient required general anesthesia to complete surgery; 3 patients receiving prilocaine (20%) and 2 patients receiving mepivacaine (13%) required 0.1 mg fentanyl intravenously to complete surgery (p=0.99). Recovery of motor function and first request of post-operative pain medication occurred after 238+/-36 min and 259+/-31 min with prilocaine, and 220+/-48 min and 248+/-47 min with mepivacaine (p=0.257 and p=0.43, respectively). Patient satisfaction was good in all studied patients. CONCLUSION: Prilocaine 1% provides adequate sensory and motor block for arthroscopic knee surgery, with a clinical profile similar to that produced by 2% mepivacaine, and may be a good option for surgical procedures of intermediate duration and not associated with severe postoperative pain.

Beating-heart coronary artery bypass graft surgery at San Raffaele Hospital: four years of experience.

OBJECTIVE: To review the database of 1,902 consecutive patients who underwent coronary artery bypass graft (CABG) surgery in the period 1998 through 2001 at this institution, and to compare the preoperative status, anesthetic management, and postoperative outcome of 364 patients with the beating-heart technique with 1,538 patients who underwent the operation on cardiopulmonary bypass. DESIGN: Observational study. SETTING: University hospital. PARTICIPANTS: Consecutive patients (n = 1,902) who underwent CABG surgery in the period 1998 through 2001. MEASUREMENTS AND MAIN RESULTS: Comparison (chi-square test) of the preoperative status shows that surgeons' choice for the beating-heart technique was based on the presence of severe preoperative comorbidities: renal impairment (p < 0.0001), chronic obstructive pulmonary disease (p < 0.04), and low ejection fraction (p < 0.0001). On a multivariate analysis, the beating-heart technique was associated with reduced transfusion needs and duration of mechanical ventilation. CONCLUSION: Beating-heart surgery is gaining popularity as a safe method for myocardial revascularization. Excellent results have been achieved with this technique in this center.

Effect of nortriptyline and paroxetine on extrapyramidal signs and symptoms: A prospective double-blind study in depressed elderly patients.

Selective serotonin-reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) have been reported to induce extrapyramidal signs and symptoms (EPS). The authors examined the change from baseline EPS, measured by an objective rating scale, in a group of elderly depressed patients participating in an ongoing randomized, double-blind comparison of nortriptyline and paroxetine. Mild baseline EPS were present in both groups. After 6 weeks of antidepressant treatment, patients in the nortriptyline group showed a significant decrease in total EPS scores. Patients in the paroxetine group showed a similar decrease in EPS from baseline, which did not reach statistical significance. There was no significant difference between nortriptyline and paroxetine in the change in EPS.

Managing antipsychotic-induced parkinsonism.

Notwithstanding the advent of clozapine and other 'atypical' antipsychotic agents, the conventional ('typical') antipsychotic agents remain in widespread use. Antipsychotic-induced parkinsonism is a highly prevalent adverse effect that may result in increased morbidity and noncompliance. Bedside examination is generally sufficient for the detection of the onset of parkinsonism and should be carried out frequently in the first 3 months of treatment. In addition to decreasing patient discomfort, monitoring for antipsychotic-induced parkinsonism also serves to identify the minimally effective dosage required for the individual patient. Several strategies are utilised in the management of antipsychotic-induced parkinsonism including dosage reduction, switching to other antipsychotic agents and the use of antiparkinsonian drugs such as anticholinergic agents and amantadine. Anticholinergic agents remain the mainstay of the pharmacological management of antipsychotic-induced parkinsonism in younger patients. Amantadine is a better tolerated agent for elderly patients, with similar efficacy to the anticholinergic agents. The routine use of prophylactic anticholinergics is not recommended and is clearly contraindicated in the elderly. An individualised risk-benefit assessment is necessary for the younger patient in whom prophylactic use of anticholinergic drugs is considered.

HIV infection in Ethiopian blood donors : prevalence; trends and future projections

The study was designed to assess the prevalence and geographic distribution of human immunodeficiency virus type 1 (HIV-1) infection in Ethiopian blood donors and to evaluate trends as well as make short term predictions on the growth of the epidemic. Donor HIV-1 screening results of six Ethiopian Red Cross Society (ERCS) blood banks; between October 1987 and September 1991; were analyzed. Repeat positivity rates in the Enzyme Linked Immune Sorbent Assay (ELISA) obtained using two different generations of welcozyme test kits were converted to confirmed western blot positivity rates in accordance with test specificities of two generation test kits obtained in low risk population locally. Trend analysis in Addis Ababa donors was made by fitting an appropriate curve to observed prevalence rates; which was used to make short term projections. During the study period; the blood screening component of the AIDS control programme was able to effectively prevent the transfusion of 3291 in HIV-1 infected blood. On the other hand a progressive increment and wide variation in HIV-1 prevalence rates of 0-5.2 per cent in 1988 and 1.6-11.6 per cent in 1991 was obtained. The overall M:F sex ratio was 1:07. The HIV-1 epidemic followed a simple exponential growth curve and the prevalence rate in Addis Ababa donors by the end of 1992 is expected to be 7.9 per cent. These data show that HIV-1 epidemic in Ethiopian blood donors are in their exponential growth phase and donor screening mechanisms utilized by our transfusion centers are effective but need to be improved significantly to screen out high risk donors. The establishment of more effective measures for the prevention and control of HIV-1 infection in general and blood safety in particular is recommended