Control Release Anesthetics to Enable an Integrated Anesthetic-mesenchymal Stromal Cell Therapeutic.

While general anesthetics control pain via consciousness regulation, local anesthetics (LAs) act by decreasing sensation in the localized area of administration by blocking nerve transmission to pain centers. Perioperative intra-articular administration of LAs is a commonly employed practice in orthopedic procedures to minimize patient surgical and post-surgical pain and discomfort. LAs are also co-administered with cellular mesenchymal stromal cell (MSC) therapies for a variety of tissue regenerative and inflammatory applications including osteoarthritis (OA) treatment; however, LAs can affect MSC viability and function. Therefore, finding an improved method to co-administer LAs with cells has become critically important. We have developed a sustained release LA delivery model that could enable the co-administration of LAs and MSCs. Encapsulation of liposomes within an alginate matrix leads to sustained release of bupivacaine as compared to bupivacaine-containing liposomes alone. Furthermore, drug release is maintained for a minimum of 4 days and the alginate-liposome capsules mitigated the adverse effects of bupivacaine on MSC viability.

The recovery of cognitive function after remifentanil-nitrous oxide anesthesia is faster than after an isoflurane-nitrous oxide-fentanyl combination in elderly patients.

UNLABELLED: We tested the hypothesis that remifentanil-nitrous oxide (N(2)O) anesthesia shortens postoperative emergence and recovery compared with an isoflurane-N(2)O-fentanyl combination in elderly patients undergoing spinal surgery. A total of 60 patients (>65 yr old) were randomly assigned to one of two groups for maintenance of anesthesia. After the induction with 3.6 +/- 1.2 mg/kg IV thiopental and endotracheal intubation facilitated with 1.4 +/- 0.5 mg/kg succinylcholine, patients were maintained with either 0.5%-1.5% isoflurane, 70% N(2)O, and up to 7 microg/kg fentanyl (iso/fent group) or 48 +/- 11 microg/kg remifentanil and 70% N(2)O (remi group). A mini-mental status examination was used to assess cognitive ability preoperatively, at 15, 30, and 60 min after arrival at the postanesthesia care unit and again 12-24 h postoperatively. The time from the conclusion of anesthesia to spontaneous respiration was similar in both groups. Times to eye opening (4.8 +/- 2.6 vs 2.3 +/- 1.1 min), extubation (6.8 +/- 3.8 vs 3.2 +/- 2.1 min), and verbalization (9.9 +/- 6.2 vs 3.9 +/- 2.6 min) were significantly shorter for the remi group (P < 0.05). Postoperative mini-mental status examination scores were significantly lower in the iso/fent group at 15 (16.3 +/- 5.8 vs 23. 7 +/- 3.3), 30 (20.2 +/- 5.2 vs 26.3 +/- 2.7), and 60 min (23.5 +/- 4.4 vs 27.5 +/- 2.0) (P < 0.001); however, the scores equalized after 12 h. Requirements for postoperative analgesics were similar in the two groups. More patients in the remi group were treated with antiemetics (21 vs 7, P = 0.06). Use of remifentanil-N(2)O for maintenance did not shorten the overall length of stay in the postanesthesia care unit; a stay is often related to multiple administrative issues, rather than cognitive recovery. IMPLICATIONS: Maintenance of anesthesia with remifentanil-nitrous oxide (N(2)O), compared with isoflurane-N(2)O-fentanyl, can safely shorten postoperative recovery of cognitive function in a geriatric population. Earlier recovery may facilitate postoperative neurological assessment. Use of remifentanil-N(2)O for maintenance did not shorten the overall length of stay in the postanesthesia care unit, a stay often related to multiple administrative issues, rather than cognitive recovery.

A comparison of remifentanil and morphine sulfate for acute postoperative analgesia after total intravenous anesthesia with remifentanil and propofol.

BACKGROUND: The transition from remifentanil intraoperative anesthesia to postoperative analgesia must be planned carefully due to the short duration of action (3-10 min) of remifentanil hydrochloride, a potent, esterase-metabolized mu-opioid agonist. This study compared the efficacy and safety of transition regimens using remifentanil or morphine sulfate for immediate postoperative pain relief in patients who had surgery under general anesthesia with remifentanil/propofol. METHODS: One hundred fifty patients who had received open-label remifentanil and propofol for intraoperative anesthesia participated in this multicenter, double-blind, double-dummy study and were randomly assigned to either the remifentanil (R) group or the morphine sulfate (M) group. Twenty minutes before the anticipated end of surgery, the propofol infusion was decreased by 50%, and patients received either a placebo bolus (R group) or a bolus of 0.15 mg/kg morphine (M group). At the end of surgery, the propofol and remifentanil maintenance infusions were discontinued and the analgesic infusion was started: either 0.1 microg x kg(-1) x min(-1) remifentanil (R group) or placebo analgesic infusion (M group). During the 25 min after tracheal extubation, remifentanil titrations in increments of 0.025 microg x kg(-1) x min(-1) and placebo boluses (R group), or 2 mg intravenous morphine boluses and placebo rate increases (M group) were administered as necessary at 5-min intervals to control pain. Patients received the 0.075 mg/kg intravenous morphine bolus (R group) or placebo (M group) at 25 and 30 min after extubation, and the analgesic infusion was discontinued at 35 min. From 35 to 65 minutes after extubation, both groups received 2-6 mg open-label morphine analgesia every 5 min as needed. RESULTS: Successful analgesia, defined as no or mild pain with adequate respiration (respiratory rate [RR] > or =8 breaths/min and pulse oximetry > or = 90%), was achieved in more patients in the R group than in the M group (58% vs. 33%, respectively) at 25 min after extubation (P < 0.05). The median remifentanil rate for successful analgesia was 0.125 microg x kg(-1) x min(-1) (range, 0.05-0.23 microg x kg(-1) x min(-1)), and the median number of 2-mg morphine boluses used was 2 (range, 0-5 boluses). At 35 min after extubation, > or = 74% of patients in both groups experienced moderate to severe pain. Median recovery times from the end of surgery were similar between groups. Transient respiratory depression, apnea, or both were the most frequent adverse events (14% for the R group vs. 6% for the M group; P > 0.05). CONCLUSIONS: Remifentanil provided safe and effective postoperative analgesia when administered at a final rate of 0.05-0.23 microg x kg(-1) x min(-1) in the immediate postextubation period. Remifentanil provided more effective postoperative analgesia than did intraoperative treatment with morphine (0.15 mg/kg) followed by morphine boluses (< or = five 2-mg boluses). The effects of remifentanil dissipated rapidly after ending the infusion, and alternate analgesia was required. Further studies are underway to define transition regimens that will improve postoperative analgesia in patients receiving anesthesia with remifentanil.

Remifentanil versus remifentanil/midazolam for ambulatory surgery during monitored anesthesia care.

BACKGROUND: This study was designed to define the appropriate dose of remifentanil hydrochloride alone or combined with midazolam to provide satisfactory comfort and maintain adequate respiration for a monitored anesthesia care setting. METHODS: One hundred fifty-nine patients scheduled for outpatient surgery participated in this multicenter, double-blind study. Patients were randomly assigned to one of two groups: remifentanil, 1 microgram/kg, given over 30 s followed by a continuous infusion of 0.1 microgram.kg-1.min-1 (remifentanil), remifentanil, 0.5 microgram/kg, given over 30 s followed by a continuous infusion of 0.05 microgram.kg-1.min-1 (remifentanil+midazolam). Five minutes after the start of the infusion, patients received a loading dose of saline placebo (remifentanil) or midazolam, 1 mg, (remifentanil+midazolam). If patients were not oversedated, a second dose of placebo or midazolam, 1 mg, was given. Remifentanil was titrated (in increments of 50% from the initial rate) to limit patient discomfort or pain intraoperatively, and the infusion was terminated at the completion of skin closure. RESULTS: At the time of the local anesthetic, most patients in the remifentanil and remifentanil+midazolam groups experienced no pain (66% and 60%, respectively) and no discomfort (66% and 65%, respectively). The final mean (+/-SD) remifentanil infusion rates were 0.12 +/- 0.05 microgram.kg-1.min-1 (remifentanil) and 0.07 +/- 0.03 microgram.kg-1.min-1 (remifentanil+midazolam). Fewer patients in the remifentanil+midazolam group experienced nauses compared with the remifentanil group (16% vs. 36%, respectively; P < 0.05). Four patients (5%) in the remifentanil group and two patients (2%) in the remifentanil+midazolam group experienced brief periods of oxygen desaturation (SpO2 < 90%) and hypoventilation (< 8 breaths/ min). CONCLUSIONS: Remifentanil alone or combined with midazolam provided adequate analgesia and maintained adequate respiration at the doses reported. The low dose of remifentanil combined with 2 mg midazolam, compared with remifentanil alone, resulted in fewer side effects, slightly greater sedation, and less anxiety.

Nifedipine-induced analgesia after epidural injection in rats.

We explored the analgesic effect of epidural nifedipine in male Sprague-Dawley rats. By using an implanted epidural catheter, the rats were given 35 microL of dimethylsulfoxide (DMSO) alone or DMSO containing 2.5, 5, 10, or 20 microM of nifedipine. Analgesia was measured by tailflick (TF) involving spinal reflexes, and by hotplate (HP) requiring an intact central nervous system. The latencies were recorded up to 120 min after the injection. The cutoff time of the noxious stimuli was 20 s in the TF and 60 s in the HP to prevent tissue damage. The TF technique revealed a significant difference from the control at doses of 5, 10, and 20 microM with no difference among the groups. Maximum latencies (cutoff time) lasted for 15, 30, and 40 min at doses of 5, 10, and 20 microM, respectively. The HP technique disclosed a dual effect: a significant decrease at the dose of 2.5 microM, no effect at 5 microM, and an increase at 10 and 20 microM. However, the median latency did not reach the cutoff time. We conclude that nifedipine, given epidurally, possesses antinociceptive properties at the dose of 5 microM and higher, detected better by the TF than HP. Our data suggest that the antinociceptive effect of nifedipine, at the studied doses, is more prominent at the spinal than the supraspinal level.

An antinociceptive effect of the intraperitoneal injection of nifedipine in rats, measured by tail-flick test.

The tail-flick (TF) technique was used to assess the antinociceptive properties of nifedipine (NIF) given intraperitoneally (i.p.). First, the most suitable intensity of the noxious stimulus (temperature of the bulb) has been ascertained and used in the main study. Male Sprague-Dawley rats received NIF, dissolved in dimethyl sulfoxide (DMSO) at the doses of 0.0, 0.5, 2, 5, 10 and 15 mg/kg, or control with no injection. For the main study, the noxious stimulus was limited to 15 sec (cut-off time) and TF latencies were recorded up to 120 min. The antinociceptive response was expressed as the area under the curve for each rat and analyzed by one-way ANOVA. The antinociceptive response to the lower doses of NIF (0.5 and 2 mg/kg) did not differ from control (no injection) and DMSO alone. Significance was found at 5, 10 and 15 mg NIF with no difference among the doses. However, there was an increasing tendency of the mean values from 0.5 to 15 mg NIF resulting in a positive correlation. The correlation coefficient was 0.32483 (p = 0.015) and regression equation Y = (19.37) x dose + 1320. Our data suggest that spinal mechanisms are involved in NIF-induced antinociception.

Alfentanil analgesia/sedation for extracorporeal shock wave lithotripsy: a comparison with general and epidural anesthesia.

An alfentanil infusion was used to produce analgesia and sedation for patients undergoing extracorporeal shock wave lithotripsy with the Dornier HM-4 lithotripter. This was compared to general and epidural anesthesia in a retrospective review of 197 consecutive patients. Total care time, anesthesia time, and recovery room time were shorter for the alfentanil analgesia/sedation group. The incidence of nausea and vomiting was similar in all three groups. Technical failure (requiring switching to general anesthesia) was not significantly different than when performed with epidural anesthesia. The technique was simple and reliable when performed by a large number of anesthesia practitioners (anesthesiologists, anesthesia residents and CRNAs).

Reflex sympathetic dystrophy and posttraumatic stress disorder. Multidisciplinary evaluation and treatment.

Reflex sympathetic dystrophy (RSD) may co-occur with posttraumatic stress disorder (PTSD). A case study is reported of a challenging adolescent patient who presented to a chronic pain service with RSD and PTSD. A multidisciplinary approach utilizing nerve-block therapy with adjunctive pharmacologic treatment, physical rehabilitation, and behavioral/cognitive psychological therapy was employed to produce a significant reduction in pain as well as a more physically and psychologically functional adolescent. The diagnosis and treatment of each disease is essential for the successful resolution of symptoms.