Late-onset presentation and phenotypic heterogeneity of the rare R377W PSEN1 mutation.

BACKGROUND AND PURPOSE: Mutations in the PSEN1 gene are the most common cause of autosomal-dominant Alzheimer's disease and have been associated with the earliest disease onset. We describe an unusual presentation of the rare R377W PSEN1 mutation with a late age of onset, and we provide for the first time in vivo pathological evidence for this mutation. METHODS: A 71-year-old female patient with progressive cognitive decline in the past 3 years and positive family history for dementia underwent neurological evaluation, neuropsychological testing, lumbar puncture, conventional brain imaging, amyloid-positron emission tomography (PET) and extensive genetic screening with a next-generation sequencing technique. RESULTS: The diagnostic workup revealed mixed behavioural and amnestic disease features on neuropsychological tests, magnetic resonance imaging, and 18-fluorodeoxyglucose (FDG)-PET. Amyloid-PET detected amyloid deposition in the frontal areas, in the parietal lobes and the precunei. The genetic screening revealed the presence of the rare R377W mutation in the PSEN1 gene. CONCLUSIONS: Extensive genetic screening is also advisable for late-onset presentations of Alzheimer's disease, especially in the presence of a positive family history or atypical clinical features.

Randomized comparison of isoflurane and sevoflurane for laparoscopic gastric banding in morbidly obese patients.

STUDY OBJECTIVE: To compare the efficacy and recovery profile of sevoflurane and isoflurane as the main anesthetics for morbidly obese patients. DESIGN: Randomized, blinded study. SETTING: Inpatients. PATIENTS: 30 ASA physical status II and III obese patients [body mass index (BMI) > 35 kg/m(2)] undergoing laparoscopic gastric banding for morbid obesity. INTERVENTIONS: After standard intravenous induction of general anesthesia and tracheal intubation, anesthesia was maintained with either sevoflurane or isoflurane as the main anesthetics. The end-tidal concentrations of the volatile drugs were adjusted to maintain systolic arterial blood pressure within +/-20% from baseline values. When the surgeon started the skin suture, the end-tidal concentration of the inhalational drug was reduced to 0.5 minimum alveolar concentration in both groups. At the last skin suture, the inhalational drug was discontinued and the vaporizator was removed to allow blinded evaluation of the emergence times. MEASUREMENTS AND MAIN RESULTS: No differences in anesthetic exposure, hemodynamic parameters, incidence of untoward events, or postoperative pain relief were reported between the two groups. Extubation, emergence, and response times were shorter after sevoflurane [6 min (3-15 min), 8 min (5-18 min), and 12 (6-25 min)] than isoflurane [10 min (6-26 min), 14 min (6-21 min), and 21 min (14-41 min)] (p = 0.001, p = 0.03, and p = 0.0005, respectively). The median time for postanesthesia care unit discharge was 15 minutes (25th-75th percentiles: 10-18 min) after sevoflurane and 27 minutes (25th-75th percentiles: 20-30 min) after isoflurane (p = 0.0005). CONCLUSIONS: Sevoflurane provides a safe and effective intraoperative control of cardiovascular homeostasis in morbidly obese patients undergoing laparoscopic gastric banding, with the advantage of a faster recovery and earlier discharge from the postanesthesia care unit than isoflurane.

Wash-in and wash-out curves of sevoflurane and isoflurane in morbidly obese patients.

BACKGROUND: The aim of this prospective, randomized study is to compare sevoflurane and isoflurane pharmacokinetics in morbidly obese patients. METHODS: With Ethical Committee approval and written informed consent, 14 obese patients (BMI >35 kg/m2), ASA physical status II, undergoing laparoscopic, silicone-adjustable gastric banding were randomly allocated to receive either sevoflurane (n=7) or isoflurane (n=7) as main anesthetic agents. General anesthesia was induced with 1 mg x kg-1 fentanyl, 6 mg x kg-1 sodium thiopental, and 1 mg x kg-1 succinylcholine followed by 0.4 mg kg-1 x h-1 atracurium bromide (doses were referred to ideal body weight). Intermittent positive pressure ventilation (IPPV) was applied using a Servo-900C ventilator with a nonrebreathing circuit and a 15 l x min-1 fresh gas flow (tidal volume: of 10 ml x kg-1; respiratory rate: 12 breaths/min; inspiratory to expiratory time ratio of 1:2) using an oxygen/air mixture (FiO2=50%), while supplemental boluses of thiopental or fentanyl were given as indicated in order to maintain blood pressure and heart rate values within +/-20% from baseline. After adequate placement of tracheal tube and stabilization of the ventilation parameters, 2% sevoflurane or 1.2% isoflurane was given for 30 min via a nonrebreathing circuit. End-tidal samples were collected at 1, 5, 10, 15, 20, 25 and 30 min, and measured using a calibrated infrared gas analyzer. General anesthesia was then maintained with the same inhalational agents, while supplemental fentanyl was given as indicated. After the last skin suture the inhalational agents were suspended, and the end tidal samples were collected at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, and 5 min. Then the lungs were manually ventilated until extubation. RESULTS: No differences in age, gender and body mass index were reported between the two groups. Surgical procedure required 91+/-13 in the sevoflurane group and 83+/-32 min in the isoflurane group. The FA/FI ratio was higher in the sevoflurane group from the 5th to the 30th min. Also the washout curve was faster in the sevoflurane group during the observation period; however, the observed differences were statistically significant only 30 and 60 sec after discontinuation of the inhalational agents. CONCLUSIONS: The results of this prospective, randomized study confirmed that sevoflurane provides more rapid wash-in and wash-out curves than isoflurane also in the morbid obese patient.

Fentanyl does not improve the nerve block characteristics of axillary brachial plexus anaesthesia performed with ropivacaine.

BACKGROUND: The aim of this prospective, randomized, double-blind study was to evaluate the effects of adding 1 microg. kg-1 fentanyl to ropivacaine 7.5 mg. ml-1 for axillary brachial plexus anaesthesia. METHODS: With Ethics Committee approval and written consent, 30 ASA physical status I-II in-patients, scheduled for orthopaedic hand procedures were randomly allocated to receive axillary brachial plexus block with 20 ml of either ropivacaine 7.5 mg. ml-1 (n=15) or ropivacaine 7.5 mg. ml-1+1 microg. ml-1 fentanyl (n=15). Nerve blocks were placed using a nerve stimulator with the multiple injection technique. A blinded observer recorded the time to onset of surgical block (loss of pinprick sensation in the innervation areas of the hand (C6-C8) with concomitant inability to flex the wrist against gravity and move the fingers when squeezing the hand) and first request for pain medication after surgery. RESULTS: No differences in demography, degree of sedation or peripheral oxygen saturation were observed between the two groups. Median (range) time required to achieve readiness for surgery was 15 min (5-36 min) with ropivacaine alone and 15 min (5-40 min) with the ropivacaine-fentanyl mixture. No differences in the intraoperative quality of nerve block were reported between the two groups. Four patients receiving ropivacaine plain and two patients receiving the ropivacaine-fentanyl mixture did not require analgesics during the first 24 h after surgery (P=0.62). The degree of pain experienced at first analgesic request in those patients asking for pain medication, as well as median consumption of postoperative analgesics, were similar in the two groups. First postoperative analgesic request was made at 11 h (25th-75th percentiles: 9.1-14 h) in patients receiving ropivacaine alone and at 11.8 h (25th-75th percentiles: 9.8-15 h) in patients receiving the ropivacaine-fentanyl mixture (P=0.99). CONCLUSION: The addition of fentanyl 1 microg. ml-1 to ropivacaine 7.5 mg. ml-1 does not improve the nerve block characteristics of axillary brachial plexus anaesthesia for orthopaedic procedures involving the hand.

Implementing sevoflurane anesthesia with small doses opioid for upper abdominal surgery. Postoperative respiratory function after either remifentanil or fentanyl.

BACKGROUND: The aim of this prospective, randomized study was to compare the effects on intraoperative cardiovascular homeostasis, recovery profile and postoperative oxygen saturation after sevoflurane anesthesia with small doses of either remifentanil or fentanyl in combination with postoperative epidural analgesia. METHODS: With Ethical Committee approval and written patient consent, 30 ASA physical status I-II patients scheduled for elective upper abdominal surgery were randomly allocated to receive sevoflurane general anesthesia implemented with small doses of either remifentanil (n = 15) or fentanyl (n = 15), followed by postoperative epidural analgesia. Remifentanil group patients received a 1 mg kg-1 bolus infused during a 60 sec period followed by a 0.15 mg kg-1 min-1 infusion; while patients of Fentanyl group were given a 3 mg kg-1 initial dose followed by 50 mg boluses as requested (according to the time to peak effect of the two drugs, the initial dose was given 5 min before induction in Fentanyl group, and 1 min before induction in Remifentanil group). Postoperatively, oxygen saturation was continuously recorded and stored on a computer during the first 12 h after surgery. SpO2 decrease < 90% for more than one minute was considered as a minor respiratory complication. RESULTS: The median sevoflurane's MAC-hour was 2.7 (1.4 - 4.9) in patients receiving remifentanil infusion and 4.1 (2.2 - 5.7) in those patients receiving fentanyl during surgery (P = 0.005). However, no differences in the recovery times were observed between the two groups. Similar pain relief was reported during coughing in the two studied groups at discharge from the recovery area and during the following study period. No major respiratory complication was observed throughout the study. Oxygen therapy was required in three patients of Fentanyl group only 20% (P = 0.22); however, 11 patients in the same group (73%) showed at least one minor respiratory complication (SpO2 < 90% for more than 1 min), with a median of 1 (range 0 - 12) episode per patient, compared with no episode in Remifentanil group (P = 0.0005). CONCLUSIONS: Implementing sevoflurane anesthesia with very small remifentanil infusion provides a safe and effective hemodynamic control reducing sevoflurane consumption during the procedure, and produces less respiratory effects postoperatively as compared with intermittent bolus administration of fentanyl.

Lidocaine versus ropivacaine for continuous interscalene brachial plexus block after open shoulder surgery.

BACKGROUND: This study compared the postoperative infusion of 1% lidocaine and 0.2% ropivacaine for continuous interscalene analgesia in patients undergoing open shoulder surgery. METHODS: Forty patients undergoing open shoulder surgery received an interscalene brachial plexus block with 30 ml of either 1.5% lidocaine (n = 20) or 0.5% ropivacaine (n = 20), followed by a continuous patient-controlled interscalene analgesia with 1% lidocaine or 0.2% ropivacaine, respectively. A blinded observer recorded the quality of analgesia and recovery of motor function during the first 24 h of infusion. RESULTS: Onset of the block occurred after 7.5 (5-40) min with lidocaine and 30 (10-60) min with ropivacaine (P = 0.0005). Postoperative pain intensity was higher with lidocaine than ropivacaine for the first 8 h of infusion. The ratio between boluses given and demanded from the pump was 0.5 (0.13-0.7) with lidocaine and 0.7 (0.4-1.0) with ropivacaine (P = 0.005). Rescue IV tramadol was required during the first 24 h of infusion by 16 patients of the lidocaine group (84%) and eight patients of the ropivacaine group (46%) (P = 0.05). At the 16 h and 24 h observation times a larger proportion of patients receiving ropivacaine had complete regression of motor block (70% and 95%) than patients receiving lidocaine (50% and 55%) (P = 0.05 and P = 0.013, respectively). CONCLUSIONS: Although 1% lidocaine can be effectively used for postoperative patient-controlled interscalene analgesia, 0.2% ropivacaine provides better pain relief and motor function.