Reaction of a polydentate cysteine-based ligand and its nickel(ii) complex with electrophilic and nucleophilic methyl-transfer reagents - from S-methylation to acetyl coenzyme A synthase reactivity.

The L-cysteine derived N2S2 ligand precursor H2L and its nickel(ii) complex L2Ni2 were investigated with respect to their behaviour in contact with electrophilic and nucleophilic methylation reagents (H2L = (N,N'-dimethyl-(2R,5R)-bis-(sulfanylmethyl)-piperazine). Treatment of deprotonated L(2-) with MeI led to the selective methylation of the thiolate groups thus generating a novel potential ligand, Me2L, which is neutral and contains two thioether donors. The coordinating properties of Me2L were demonstrated by the synthesis of a first nickel(ii) complex: reaction with NiBr2 led to a mononuclear complex 2 where all donor atoms coordinate to the nickel ion, which completes its octahedral coordination sphere by the two bromide ligands. If, however, the complex [LNi]2 (1) is treated with MeI only one thiolate function per ligand moiety is methylated, while the other one remains a thiolate. This leads to [MeLNi](+) complex metal fragments, which trimerize including a µ3-bridging iodide ion to give the compound 3 that was tested with regards to ACS reactivity. While it behaved inert towards CO, attempts to replace the bridging iodide ligand by methyl units in reactions with nucleophilic methylation reagents led to a product, which could not be identified but reacted with CO. Work-up showed that this protocol had converted the thiolate function of MeL(-) into a thioester function, which corresponds to an ACS-like reactivity.

Cerebral protection.

Ischaemic/hypoxic insults to the brain during surgery and anaesthesia can result in long-term disability or death. Advances in resuscitation science encourage progress in clinical management of these problems. However, current practice remains largely founded on extrapolation from animal studies and limited clinical investigation. A major step was made with demonstration that rapid induction of mild sustained hypothermia in comatose survivors of out-of-hospital ventricular fibrillation cardiac arrest reduces death and neurological morbidity with negligible adverse events. This provides the first irrefutable evidence that outcome can be favourably altered in humans with widely applicable neuroprotection protocols. How far hypothermic protection can be extended to global ischaemia of other aetiologies remains to be determined. All available evidence suggests an adverse response to hyperthermia in ischaemic or post-ischaemic brain. Management of other physiological values can have dramatic effects in experimental injury models and this is largely supported by available clinical data. Hyperoxaemia may be beneficial in transient focal ischaemia but deleterious in global ischaemia. Hyperglycaemia causes exacerbation of most forms of cerebral ischaemia and this can be abated by restoration of normoglycaemia. Studies indicate little, if any, role for hyperventilation. There is little evidence in humans that pharmacological intervention is advantageous. Anaesthetics consistently and meaningfully improve outcome from experimental cerebral ischaemia, but only if present during the ischaemic insult. Emerging experimental data portend clinical breakthroughs in neuroprotection. In the interim, organized large-scale clinical trials could serve to better define limitations and efficacy of already available methods of intervention, aimed primarily at regulation of physiological homeostasis.

Cardiopulmonary bypass induces neurologic and neurocognitive dysfunction in the rat.

BACKGROUND: Neurocognitive dysfunction is a common complication of cardiac surgery using cardiopulmonary bypass (CPB). Elucidating injury mechanisms and developing neuroprotective strategies have been hampered by the lack of a suitable long-term recovery model of CPB. The purpose of this study was to investigate neurologic and neurocognitive outcome after CPB in a recovery model of CPB in the rat. METHODS: Fasted rats (n = 10) were subjected to 60 min of normothermic (37.5 degrees C) nonpulsatile CPB using a roller pump and a membrane oxygenator. Sham-operated controls (n = 10) were not subjected to CPB. Neurologic outcome was assessed on days 1, 3, and 12 after CPB using standardized functional testing. Neurocognitive outcome, defined as the time (or latency) to finding a submerged platform in a Morris water maze (an indicator of visual-spatial learning and memory), was evaluated daily from post-CPB days 3-12. Histologic injury in the hippocampus was also evaluated. RESULTS: Neurologic outcome was worse in the CPB versus the sham-operated controls at all three measurement intervals (P < 0.001). The CPB group also had longer water maze latencies compared with the sham-operated controls (P = 0.004), indicating significant neurocognitive dysfunction after CPB. No difference in histologic injury between groups was observed. CONCLUSIONS: CPB caused both neurologic and neurocognitive impairment in a rodent recovery model. This model could potentially facilitate the investigation of CPB-related injury mechanisms and possible neuroprotective interventions.

Does functional ability in the postoperative period differ between remifentanil- and fentanyl-based anesthesia?

STUDY OBJECTIVES: To compare patients' functional ability in the 24-hour postoperative period following a remifentanil compared to a hypnotic-fentanyl-treated anesthesia regimen using a 24-Hour Functional Ability Questionnaire. DESIGN: Prospective, 1:1 single-blind, randomized, controlled effectiveness study. SETTING: Multicenter study including 156 hospitals and ambulatory surgery facilities. PATIENTS: 2438 patients (1496 outpatients and 942 inpatients) 18 years of age or older, scheduled for elective surgeries under general endotracheal anesthesia, with an expected duration of unconsciousness of > or =30 minutes. INTERVENTIONS: Patients were randomized to receive either intravenous remifentanil (0.5 microg/kg/min for induction and intubation; with the infusion rate decreased to 0.25 microg/kg/min after intubation) or fentanyl (administered according to anesthesiologists' usual practice) as the opioid during surgery. Concomitant hypnotic drugs were propofol and/or isoflurane (with or without nitrous oxide) titrated according to protocol. Transition analgesia with either morphine or fentanyl was given in the remifentanil patients and at the discretion of the anesthesiologists in the fentanyl patients. MEASUREMENTS: A validated set of measurements of functional ability, rather than more traditional clinical psychological methods, to compare the recovery of patients from remifentanil- and fentanyl-treated anesthetic regimens up to 24 hours after surgery. MAIN RESULTS: Remifentanil was statistically superior to fentanyl for the four functional assessments evaluated: walking without dizziness, thinking clearly, concentration, and communicating effectively. These differences reflect events occurring within the first 24 hours after anesthesia and surgery. CONCLUSIONS: A remifentanil-treated anesthetic demonstrated earlier return to some functions than a fentanyl-treated technique. Although functional assessment is a field that is still in its infancy, a questionnaire to assess functional ability during the 24 hours after anesthesia may provide more practical information about anesthetic recovery than previously used, traditional psychomotor evaluations.

Hemodynamics and emergence profile of remifentanil versus fentanyl prospectively compared in a large population of surgical patients.

STUDY OBJECTIVE: To compare the responses to, and hemodynamics associated with surgical stress, recovery profiles, and anesthesiologists' satisfaction following balanced general anesthesia using either remifentanil or fentanyl in a large-scale population. DESIGN: Prospective, 1:1 single blind, randomized, controlled effectiveness study in which patients received either remifentanil or fentanyl in combination with a hypnotic-based anesthesia regimen of either isoflurane or propofol. SETTING: Multicenter study including 156 hospitals and ambulatory surgery facilities. PATIENTS: 2,438 patients (1,496 outpatients and 942 inpatients), 18 years of age or older, scheduled for elective surgeries under general endotracheal anesthesia, with an expected duration of unconsciousness > or =30 minutes. INTERVENTIONS: Patients were randomized to receive either intravenous (IV) remifentanil (0.5 microg/kg/min for induction and intubation, with the infusion rate decreased to 0.25 microg/kg/min after intubation) or IV fentanyl (administered according to anesthesiologists' usual practice) as the opioid during surgery. Concomitant hypnotic drugs were either propofol and/or isoflurane (with or without nitrous oxide) titrated according to protocol. Transition analgesia with either morphine or fentanyl was given to the remifentanil patients and, at the anesthesiologists' discretion, in the fentanyl patients. MEASUREMENTS: Vital signs, adverse events, and emergence profiles were assessed and recorded. Recovery profile was assessed by recording time spent in the postanesthesia care unit and step-down recovery unit, number and timing of adverse events, timing and dosage of rescue medications, and time to eligibility for discharge (to home or to hospital room). Anesthesiologists' satisfaction with the anesthetic regimen was assessed at the end of surgery. MAIN RESULTS: Remifentanil-treated patients exhibited lower systolic and diastolic blood pressures (by 10-15 mmHg) and lower heart rates (by 10-15 bpm) intraoperatively compared to the fentanyl-treated patients. This difference promptly disappeared on emergence. Remifentanil-treated patients responded to verbal command, left the operating room, and (for outpatients) were discharged home sooner than fentanyl-treated patients. Anesthesiologists rated the predictability of response to intraoperative titration, assessment of hemodynamic profiles, and the quality of anesthesia higher in the remifentanil-treated patients. CONCLUSIONS: This study confirms previous observations on the hemodynamic properties associated with remifentanil and extends these to a wider context than previously reported. These characteristics provide clinicians with an alternative in opioid-based anesthesia.

Interscalene brachial plexus block with continuous intraarticular infusion of ropivacaine.

Providing intraarticular analgesia with a continuous infusion of local anesthetic via a disposable infusion pump has gained popularity. Despite the prevalence of this technique, data comparing this method of analgesia to conventional regional anesthesia are not available. We present a prospective study that compared a single-dose interscalene block with a single-dose interscalene block plus continuous intraarticular infusion of local anesthetic. Forty patients scheduled for shoulder arthroscopy were entered in this prospective, double-blinded study. All patients received an interscalene brachial plexus block as their primary anesthetic. Patients were randomly assigned to 1 of 2 groups: 1. interscalene block with 1.5% mepivacaine (40 mL) followed by a postoperative intraarticular infusion of 0.5% ropivacaine at 2 mL/h, or 2. interscalene block with 0.5% ropivacaine (40 mL) followed by a postoperative intraarticular infusion of 0.9% saline (placebo) at 2 mL/h. Postoperative infusions were maintained for 48 h. Visual analog scale pain scores and postoperative oxycodone consumption were measured for 48 h. Visual analog scale scores at rest and with ambulation in the Mepivacaine/Intraarticular Ropivacaine group were reduced when compared with the Ropivacaine/Saline group (rest: P = 0.003, ambulation: P = 0.006). Oxycodone consumption was also decreased (28 +/- 21 mg vs 44 +/- 28 mg, P = 0.046), respectively. We conclude that a brachial plexus block with 1.5% mepivacaine and a continuous intraarticular infusion of 0.5% ropivacaine at 2 mL/h provides improved analgesia for minor surgery at 24 and 48 h versus a single-injection interscalene block with 0.5% ropivacaine.

Neurological injury during cardiopulmonary bypass in the rat.

Cerebral injury is a well-known complication of cardiac surgery. Investigations of both injury mechanisms and neuroprotective strategies have partially been limited by the lack of an adequate preclinical model of small animal cardiopulmonary bypass (CPB). We sought to determine if neurological injury could be demonstrated in a recovery model of complete CPB in the rat. Rats (n = 5) underwent 45 min of normothermic CPB followed by 24 h of recovery. Compared to sham-operated rats (n = 5), the CPB group showed a worse neurological outcome score (median, 25-75th percentile) compared to controls (5, 4-7 vs 9, 8-9, p = 0.016). This rat model of CPB may allow for the study of CPB-associated neurological injury.

Interscalene brachial plexus block with a continuous catheter insertion system and a disposable infusion pump.

Continuous interscalene brachial plexus blockade traditionally requires a hospital stay for local anesthetic infusion, and achieving consistent catheter insertion may be difficult. Incorporating long-acting pain relief from a continuous peripheral nerve block, with a reliable method of catheter insertion, and a self-contained infusion system would be a valuable asset for short-stay care. We compared the efficacy of single injection interscalene brachial plexus blockade to a continuous peripheral nerve block, with an insulated Tuohy system and a disposable infusion pump. Forty adult patients scheduled for open rotator cuff repair were entered in this randomized, double-blinded, placebo-controlled study. Patients received an interscalene brachial plexus blockade and a continuous peripheral nerve catheter as their primary anesthetic and then, were assigned to receive one of two different postoperative infusions: either 0.2% ropivacaine at 10 mL/h via a disposable infusion pump or normal saline at 10 mL/h via a disposable infusion pump (n = 18-20 per group). Visual analog pain scores and postoperative morphine consumption were measured for 24 h. The ropivacaine group showed less pain than the placebo group (P: = 0.0001) between 12 and 24 h after the initial injection of local anesthetic. In addition, initial interscalene blockade was successful in all patients and all redosed catheters were functional after 24 h with the continuous catheter insertion system. We conclude that it is possible to achieve a high rate of successful catheter placement and analgesia by using the continuous catheter insertion system and a disposable infusion pump in the ambulatory setting. This method of analgesia may offer improved pain relief after outpatient rotator cuff repair.

Periischemic cerebral blood flow (CBF) does not explain beneficial effects of isoflurane on outcome from near-complete forebrain ischemia in rats.

BACKGROUND: Isoflurane improves outcome from near-complete forebrain ischemia in rats compared with fentanyl-nitrous oxide (N2O). Sympathetic ganglionic blockade with trimethaphan abolishes this beneficial effect. To evaluate whether anesthesia-related differences in cerebral blood flow (CBF) may explain these findings, this study compared regional CBF before, during, and after near-complete forebrain ischemia in rats anesthetized with either isoflurane (with and without trimethaphan) or fentanyl-nitrous oxide. METHODS: Fasted, normothermic isoflurane anesthetized Sprague-Dawley rats were prepared for near-complete forebrain ischemia (10 min of bilateral carotid occlusion and mean arterial pressure = 30 mmHg). After surgery, rats were anesthetized with either 1.4% isoflurane (with or without 2.5 mg of trimethaphan intravenously at onset of ischemia) or fentanyl-nitrous oxide (25 microgram. kg-1. h-1. 70% N2O-1). Regional CBF was determined (14C-iodoantipyrine autoradiography) before ischemia, 8 min after onset of ischemia, and 30 min after onset of reperfusion. RESULTS: Regional CBF did not differ significantly among groups at any measurement interval. Ischemia caused a marked flow reduction to 5% or less of baseline (P < 0.001) in selectively vulnerable regions, such as the cortex, caudoputamen and hippocampus, whereas flow in the brain stem and cerebellum was preserved. Reperfusion at 30 min was associated with partial restoration of flow to 35-50% of baseline values in ischemic structures. CONCLUSIONS: The results indicate that improved histologic-behavioral outcome provided by isoflurane anesthesia cannot be explained by differential vasodilative effects of the anesthetic states before, during, or after severe forebrain ischemia. This study also shows severe postischemic delayed hypoperfusion that was not affected by choice of anesthetic or the presence of trimethaphan. Mechanisms other than effects on periischemic CBF must be responsible for beneficial effects of isoflurane in this model.

Is there a learning curve associated with the use of remifentanil?

UNLABELLED: This study prospectively determined whether there was a learning curve with the use of remifentanil, as indicated by decreased hemodynamic variability, improved recovery profile, and decreased incidence of opioid-related adverse events with increasing experience. Patients undergoing diverse surgical procedures (outpatient [n = 1340] and inpatient [n = 560]) were enrolled by investigators (n = 190) who had no previous experience with remifentanil use. Each investigator enrolled 10 patients. A standardized protocol for administration of remifentanil was used. Data were analyzed to determine differences between the first three patients and the last three patients enrolled for each anesthesiologist in the study. There were no differences in hemodynamic variables between the first triad and the last triad in either outpatients or inpatients. Requirements for hypnotic drugs and the doses of remifentanil used were also similar between groups. Analgesic medications administered at the end of surgery and in the postanesthesia care unit (PACU) were similar between groups, except that the last triad in the outpatient group received smaller doses of fentanyl compared with the first triad. Times to response to verbal command, tracheal extubation, and operating room discharge did not differ between groups. However, patients in the last triad undergoing outpatient surgery had shorter times to eligibility for PACU discharge, but times to eligibility for discharge home did not differ. The overall incidence of all adverse events (i.e., hypotension, hypertension, muscle rigidity, respiratory depression, apnea, nausea, and vomiting) was less in the last triad as compared with the first triad. When analyzed separately, only the incidence of vomiting (in the outpatient group) was decreased in the last triad as compared with the first triad. This study suggests that there is a learning curve that aids reduction of minor adverse effects associated with the use of analgesic medications administered at the end of surgery in outpatients, which might have reduced the incidence of postoperative vomiting and the duration of PACU stay. IMPLICATIONS: This study demonstrated that anesthesiologists rapidly acquire the ability to use remifentanil with limited experience. However, there is a learning curve that aids reduction of minor adverse effects associated with the use of analgesic medications administered at the end of surgery in outpatients, which might have reduced the incidence of postoperative vomiting and the duration of postanesthesia care unit stay.

A randomized, double-blinded comparison of ondansetron, droperidol, and placebo for prevention of postoperative nausea and vomiting after supratentorial craniotomy.

UNLABELLED: Nausea or vomiting occurs frequently after craniotomy. Because of the need for frequent postoperative neurological assessment, an effective antiemetic with minimal sedative side effects is needed. Therefore, we compared ondansetron to droperidol in a randomized, double-blinded, placebo-controlled study. A total of 60 adults requiring elective supratentorial craniotomy received standardized IV anesthesia with 4 mg of ondansetron, 0.625 mg of droperidol, or placebo at skin closure. The incidence of postoperative nausea, emesis, pain and sedation scores, and rescue antiemetic use were recorded at 0, 0.5, 1, 4, 8, 12, 24, and 48 h. All groups were demographically similar. Differences existed for cumulative 8, 12, and 24 h incidences of nausea (24 h, P = 0.03) and emesis (24 h, P = 0.04). Within 4 h, when maximal effect could be expected from treatment, 20% of the ondansetron group, 25% of the droperidol group and 50% of the placebo group received rescue antiemetic (P = 0.12). No differences in pain (P = 0.82) or sedation (P = 0.74) scores were detected. Both ondansetron and droperidol prevent nausea; however, only droperidol reduces emesis after supratentorial craniotomy. The dose of droperidol used was not more sedating than ondansetron. Sustained reduction in nausea and emesis over 24 h indicates a preemptive benefit of prophylactic antiemetic in this surgical population. IMPLICATIONS: Nausea and vomiting after brain surgery are particularly troubling, because effective treatment may cause sedation, making postoperative neurological assessment difficult. Our study shows that both ondansetron and droperidol are effective in reducing nausea, and that droperidol is particularly effective in reducing vomiting. Neither drug caused more sedation than placebo.

Assessing a tool to measure patient functional ability after outpatient surgery.

UNLABELLED: The "24-Hour Functional Ability Questionnaire" (24hFAQ) was developed to measure final recovery and satisfaction 24 h after surgery. We used structured interviews preoperatively to measure baseline patient concerns, and up to 24 h after discharge, to assess patient function and satisfaction. The primary objective was to assess the validity of the newly developed 24hFAQ in the postoperative outpatient setting. The criteria assessed were 1) CONTENT: comparison with expert opinion and patients' views and response frequency distributions for asymptotes and irrelevance, 2) Construct: contribution of cognitive, physical, and satisfaction domains to postoperative functional ability, 3) Discrimination: comparing mean clinical end points with patient satisfaction, and 4) Criterion (predictive) validity: testing that related constructs are best correlated. CONTENT validity was supported by the appropriate frequency distribution of subject responses, by the lack of floor or ceiling effects, and by <2% of responses indicating irrelevance. Construct validity was supported by moderate-to-strong positive interitem correlations within the cognitive and physical domains as predicted a priori. Discriminant validity support was mixed: key symptoms were associated with adverse patient satisfaction, but operating room and postanesthesia care unit residence times were unrelated. Criterion validity was supported by the finding that preoperative concern with key symptoms was independent of postoperative outcomes. The validity assessment presented was the first assessment of the measurement capability of the 24hFAQ in an outpatient postoperative population. These results provide overall support for the validity of the 24hFAQ for use in outpatient populations. IMPLICATIONS: This study assessed the validity of a novel functional ability questionnaire that measured functional status after recovery from anesthesia and satisfaction 24 h after outpatient surgery. The content, construct, discriminant, and criterion (predictive) validities demonstrated the utility of this assessment instrument in the outpatient setting.

The effects of anesthetics on stress responses to forebrain ischemia and reperfusion in the rat.

UNLABELLED: Rats exposed to forebrain ischemia have reduced injury when anesthetized with isoflurane versus fentanyl + N(2)O. The protection caused by isoflurane is reversed by trimethaphan. We hypothesized that these anesthetic-dependent effects on ischemic outcome can be associated with altered stress responses to ischemia. Rats were randomized to four treatments: isoflurane; fentanyl + N(2)O; isoflurane + trimethaphan; or isoflurane + metyrapone. Severe forebrain ischemia was then induced for 10 min. Plasma and brain corticosterone, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-6 were assayed. Plasma corticosterone concentrations were similar in the isoflurane and isoflurane + trimethaphan groups, but greater than in the fentanyl + N(2)O and isoflurane + metyrapone groups. Brain corticosterone was similar among all groups except isoflurane + metyrapone, in which values were markedly reduced. The addition of metyrapone to isoflurane also reduced plasma TNF-alpha; however, values among other groups were similar. There were no differences among groups for brain TNF-alpha. Plasma IL-6 concentrations were below the limit of detection. Brain IL-6 concentrations were increased by ischemia; however, there was no difference among groups. In conclusion, there were no differences between the isoflurane and isoflurane + trimethaphan groups for any of the measured stress markers. Further, there was little difference between the isoflurane and fentanyl + N(2)O groups, except for plasma corticosterone concentration. Accordingly, isoflurane neuroprotection and its reversal by trimethaphan appear to be independent of effects on the stress responses measured in this study. IMPLICATIONS: Differential anesthetic effects on ischemic outcome are independent of effects on adrenergic/noradrenergic responses to ischemia. The absence of a consistent differential effect of anesthetics on either corticosterone or cytokine responses to ischemia serves to further refute the hypothesis that isoflurane neuroprotection can be attributed to dampening of adverse stress responses to ischemic insults.

A comparison of remifentanil and fentanyl in patients undergoing surgery for intracranial mass lesions.

UNLABELLED: We compared the effects of remifentanil versus fentanyl during surgery for intracranial space-occupying lesions. Patients were randomly assigned to receive either remifentanil (0.5 microg. kg(-1). min(-1) IV during the induction of anesthesia reduced to 0.25 microg. kg(-1). min(-1) after endotracheal intubation; n = 49) or fentanyl (dose per usual practice of the anesthesiologist; n = 54). Anesthesia maintenance doses of isoflurane, nitrous oxide, and opioid were at the anesthesiologist's discretion for both groups. There were no differences between opioid groups for the frequency of responses (hemodynamic, movement, and tearing) to intubation, pinhead holder placement, skin incision, or closure of the surgical wound. Adverse event frequencies were similar between groups. Times to follow verbal commands (P < 0.001) and tracheal extubation (P = 0. 04) were more rapid for remifentanil. The percentage of patients with a normal recovery score (were alert or arousable to quiet voice, were oriented, were able to follow commands, had motor function unchanged from their preoperative evaluation, were not agitated, and had modified Aldrete Scores of 9-10) at 10 min after surgery was more for remifentanil (45% vs 18%; P = 0.005). By 20 min, no difference between groups existed (P = 0.27). Anesthesiologists used more isoflurane in the fentanyl group (4.22 vs 1.93 minimum alveolar anesthetic concentration hours). Neurosurgeons, blinded to treatment group, favored the use of remifentanil. Similar frequencies of light anesthesia responses and other adverse events suggest that intraoperative depths of anesthesia were similar in the two groups. Under these conditions, emergence was more rapid with remifentanil. This is consistent with the necessity for less isoflurane use in the remifentanil group and the intrinsic rapid clearance of this opioid. IMPLICATIONS: Patients given remifentanil-based anesthesia for craniotomy had faster recovery times from anesthesia than did those given fentanyl-based anesthesia.

The effects of aprotinin on outcome from cerebral ischemia in the rat.

UNLABELLED: The administration of aprotinin has been associated with a reduction in cardiac surgery-related stroke. Intrinsic neuroprotective properties of this drug have not been evaluated in laboratory outcome models of cerebral ischemia. The purpose of this study was to determine whether aprotinin exhibits neuroprotective effects against either global or focal cerebral ischemia in the rat. Fasted rats were administered aprotinin (30,000 or 60,000 KIU/kg) or vehicle (0.9% NaCl) IV before global ischemia (10 min bilateral carotid occlusion with mean arterial pressure 30 mm Hg) or focal ischemia (75 min of transient middle cerebral artery occlusion [MCAO]). Five days after global ischemia, the percentage of dead hippocampal CA1 neurons (mean +/- SD) was similar among the groups (small-dose aprotinin: 49+/-31, n = 15; large-dose aprotinin: 55+/-31, n = 13; vehicle: 47+/-31, n = 16; P = 0.74). After 7 days' recovery from MCAO, no difference among the groups was observed for either neurologic score (P = 0.99) or cerebral infarct volume (small-dose aprotinin: 136+/-80 mm3, n = 23; large-dose aprotinin: 132+/-101 mm3, n = 11; vehicle: 121+/-81 mm3, n = 21; P = 0.87). IMPLICATIONS: Aprotinin offers no neuroprotection against either global or focal cerebral ischemia in the rat when administered as a single preischemic bolus.

A comparison of 0.5% bupivacaine, 0.5% ropivacaine, and 0.75% ropivacaine for interscalene brachial plexus block.

UNLABELLED: The onset time and duration of action of ropivacaine during an interscalene block are not known. The potentially improved safety profile of ropivacaine may allow the use of higher concentrations to try and speed onset time. We compared bupivacaine and ropivacaine to determine the optimal long-acting local anesthetic and concentration for interscalene brachial plexus block. Seventy-five adult patients scheduled for outpatient shoulder surgery under interscalene block were entered into this double-blind, randomized study. Patients were assigned (n = 25 per group) to receive an interscalene block using 30 mL of 0.5% bupivacaine, 0.5% ropivacaine, or 0.75% ropivacaine. All solutions contained fresh epinephrine in a 1:400,000 concentration. At 1-min intervals after local anesthetic injection, patients were assessed to determine loss of shoulder abduction and loss of pinprick in the C5-6 dermatomes. Before discharge, patients were asked to document the time of first oral narcotic use, when incisional discomfort began, and when full sensation returned to the shoulder. The mean onset time of both motor and sensory blockade was <6 min in all groups. Duration of sensory blockade was similar in all groups as defined by the three recovery measures. We conclude that there is no clinically important difference in times to onset and recovery of interscalene block for bupivacaine 0.5%, ropivacaine 0.5%, and ropivacaine 0.75% when injected in equal volumes. IMPLICATIONS: In this study, we demonstrated a similar efficacy between equal concentrations of ropivacaine and bupivacaine. In addition, increasing the concentration of ropivacaine from 0.5% to 0.75% fails to improve the onset or duration of interscalene brachial plexus block.

Paravertebral somatic nerve block for outpatient inguinal herniorrhaphy: an expanded case report of 22 patients.

BACKGROUND AND OBJECTIVES: Inguinal herniorrhaphy is a common outpatient surgical procedure. However, anesthetic techniques for inguinal herniorrhaphy are still associated with numerous side effects. Paravertebral somatic nerve block (PSNB) has the potential advantage to offer unilateral abdominal wall anesthesia and long-lasting pain relief with minimal side effects. We report our initial trial of PSNB for outpatient inguinal herniorrhaphy. METHODS: Twenty-two patients received a PSNB at T10 to L2 using 5 mL of 0.5% bupivacaine with epinephrine 1:400,000 at each of the five levels. The onset of surgical anesthesia, duration of analgesia, side effects, and patient satisfaction with the technique were documented. RESULTS: Surgical anesthesia occurred 15-30 minutes after injection. Two patients had a failed block. The mean +/- SD time to onset of discomfort was 14 +/- 11 hours. Time until first narcotic requirement was 22 +/- 18 hours. Thirteen patients (n = 20) had no incisional discomfort 10 hours or longer after their blocks. Three patients had epidural spread. Most patients were very satisfied with their anesthetic technique. CONCLUSIONS: The results of our initial experience suggest that PSNB is a potentially safe and effective technique. In general, the block provided long-lasting pain relief in most patients with few side effects. A randomized study comparing paravertebral blocks with conventional anesthesia choices is suggested given the findings in this initial series of patients.

Postoperative nausea and vomiting. A retrospective analysis in patients undergoing elective craniotomy.

Nausea and vomiting are important complications after craniotomy, for which there are little published epidemiologic data. We retrospectively examined the incidence of postcraniotomy nausea and vomiting to define risk factors. Medical records from 199 adults undergoing elective craniotomy were identified. Data extracted from surgery and the initial 48 hours postoperatively included gender, age, supratentorial versus infratentorial craniotomy, type of anesthesia (general versus monitored anesthesia care), intraoperative fentanyl dose, duration of anesthesia, antiemetic administration intraoperatively and postoperatively, and incidence of postoperative nausea, emesis, and opioid use. Postoperative nausea was recorded in 99 patients (50%) and emesis in 78 patients (39%). Postoperative opioids were administered to 170 patients (85%). Antiemetics were given intraoperatively to 13 patients (7%) and postoperatively to 121 patients (61%). More women (61%) than men (37%) had nausea (P = 0.001); emesis (women = 46%; men = 31%, P = 0.03); and postoperative antiemetic use (women = 69%; men = 51%, P = 0.013). The incidence of postoperative nausea (P = 0.04) and vomiting (P = 0.06) was greater in patients having infratentorial surgery. Emesis was more frequent in younger patients (P = 0.03). Postoperative nausea and vomiting were independent of anesthetic duration, fentanyl dose, or postoperative opioid use and occurred with similar frequency after general anesthesia or monitored anesthesia care. We conclude that postoperative nausea and vomiting occur frequently after craniotomy. Infratentorial surgery, female gender, and younger age are significant risk factors for this complication.

Intact cerebral blood flow reactivity during remifentanil/nitrous oxide anesthesia.

Remifentanil hydrochloride is a new opioid rapidly metabolized by blood and tissue esterases. The swift degradation accounts for the elimination half-life (t1/2 beta) of < 10 min. An anesthetic agent allowing more rapid postoperative assessment of the neurosurgical patient would be beneficial. This study examined the effect of remifentanil on cerebral blood flow (CBF) reactivity to changes in the arterial pressure of carbon dioxide (PaCO2). Cerebral blood flow was measured with intravenous 133-Xenon during remifentanil/ nitrous oxide (N2O) anesthesia in 10 patients undergoing craniotomy. Cerebrovascular reactivity was determined by repeating CBF measurements after the addition of carbon dioxide (CO2) to the inspired gas mixture. The CBF increased from 21 +/- 6 to 31 +/- 7 ml/100 g/min as the PaCO2 increased from 27 +/- 4 to 36 +/- 3 mm Hg. The relative CBF reactivity was 3.6 +/- 1.2%/mm Hg CO2. During the CBF determinations, the doses of remifentanil administered were not significantly different (0.38 +/- 0.18 microgram/kg/min at hypocapnia vs. 0.34 +/- 0.16 microgram/kg/min at normocapnia). Electroencephalographic monitoring showed a spectral edge frequency of 26 +/- 1 Hz before induction, 25 +/- 1 Hz during maintenance of the remifentanil/N2O anesthetic (0.32 +/- 0.15 microgram/kg/ min), 24 +/- 1 Hz during hypocapnic CBF determination, and 24 +/- 2 Hz during normocapnic CBF determination. At the completion of the procedure, the patients responded to commands within 3.6 +/- 2.5 min and were extubated 7.2 +/- 4.5 min after the remifentanil/N2O was discontinued. In conclusion, absolute CBF values during remifentanil/N2O are similar to previously reported CBF values during fentanyl/N2O and isoflurane/N2O anesthesia, and cerebrovascular reactivity to CO2 remains intact.

Comparison of remifentanil and fentanyl in patients undergoing craniotomy for supratentorial space-occupying lesions.

BACKGROUND: Remifentanil hydrochloride is an ultra-short-acting, esterase-metabolized mu-opioid receptor agonist. This study compared the use of remifentanil or fentanyl during elective supratentorial craniotomy for space-occupying lesions. METHODS: Sixty-three adults gave written informed consent for this prospective, randomized, double-blind, multiple-center trial. Anesthesia was induced with thiopental, pancuronium, nitrous oxide/oxygen, and fentanyl (n = 32; 2 micrograms.kg.-1. min-1) or remifentanil (n = 31; 1 mu.kg-1.min-1). After tracheal intubation, infusion rates were reduced to 0.03 microgram.kg-1.min-1 (fentanyl) or 0.2 microgram.kg-1.min-1 (remifentanil) and then adjusted to maintain anesthesia and stable hemodynamics. Isoflurane was given only after specified infusion rate increases had occurred. At the time of the first burr hole, intracranial pressure was measured in a subset of patients. At bone flap replacement either saline (fentanyl group) or remifentanil (approximately 0.2 microgram.kg-1.min-1) were infused until dressing completion. Hemodynamics and time to recovery were monitored for 60 min. Analgesic requirements and nausea and vomiting were observed for 24 h. Neurological examinations were performed before operation and on postoperative days 1 and 7. RESULTS: Induction hemodynamics were similar. Systolic blood pressure was greater in the patients receiving fentanyl after tracheal intubation (fentanyl = 127 +/- 18 mmHg; remifentanil = 113 +/- 18 mmHg; P = 0.004). Intracranial pressure (fentanyl = 14 +/- 13 mmHg; remifentanil = 13 +/- 10 mmHg) and cerebral perfusion pressure (fentanyl = 76 +/- 19 mmHg; remifentanil = 78 +/- 14 mmHg) were similar. Isoflurane use was greater in the patients who received fentanyl. Median time to tracheal extubation was similar (fentanyl = 4 min: range = -1 to 40 min; remifentanil = 5 min: range = 1 to 15 min). Seven patients receiving fentanyl and none receiving remifentanil required naloxone. Postoperative systolic blood pressure was greater (fentanyl = 134 +/- 16 mmHg; remifentanil = 147 +/- 15 mmHg; P = 0.001) and analgesics were required earlier in patients receiving remifentanil. Incidences of nausea and vomiting were similar. CONCLUSIONS: Remifentanil appears to be a reasonable alternative to fentanyl during elective supratentorial craniotomy.