Effects of propofol on hippocampal synaptic transmission in behaving rats.

BACKGROUND: The action of propofol has been studied in vitro and in vivo, but the effects of intravenously administered propofol on synaptic transmission in freely behaving rats have not been studied before. METHODS: Rats were implanted with recording electrodes in the dentate gyrus and with stimulation electrodes in the medial perforant path (MPP). Paired pulses at different interpulse intervals (IPIs) were delivered to the MPP, and average evoked potentials were recorded in the dentate gyrus before and after a bolus of propofol (10 or 20 mg/kg administered intravenously) or control vehicle was injected via femoral vein cannula. Because of the layered structure of the hippocampus, population excitatory postsynaptic potentials and population spikes could be distinguished and analyzed. RESULTS: Propofol has no significant effect on the population excitatory postsynaptic potentials or population spike evoked by a single MPP stimulus pulse. However, paired-pulse inhibition of the dentate population spikes was increased at IPI of 20 and 30 ms. Paired-pulse inhibition of the population spike was most prominent when tail pinch response was lost (deep and moderate anesthesia), but it persisted during light anesthesia. At 200 ms IPI, paired-pulse facilitation of population spikes was observed during moderate anesthesia in most rats. CONCLUSIONS: In freely behaving rats, intravenous propofol enhanced paired-pulse inhibition at < 50 ms IPI, likely by enhancing gamma-aminobutyric acid A receptor-mediated inhibition. Propofol also increased paired-pulse facilitation at 200 ms IPI through an unknown mechanism, which may contribute to the neuroexcitatory effect of propofol.

Anesthesia for temporal lobe epilepsy surgery.

Anesthetic considerations for temporal lobectomy for refractory epilepsy include ensuring a safe and comfortable perioperative experience for the patient, providing suitable operating conditions for the surgeon, avoiding interference with intraoperative electrocorticographic (ECoG) recordings and facilitating intraoperative functional cortical mapping, if performed. Providing the conditions that simultaneously meet these requirements, using general anesthesia or local anesthesia with sedation, remains a significant challenge for the neuroanesthetist. We review issues pertinent to the choice of anesthetic technique for these procedures.

The effect of sevoflurane and isoflurane anesthesia on interictal spike activity among patients with refractory epilepsy.

UNLABELLED: The electrophysiologic effects of sevoflurane are not well characterized in humans. Among patients with refractory epilepsy, this study compared 1) electroencephalographic (EEG) interictal spike activity during wakefulness and sevoflurane anesthesia, and 2) electrocorticographically (ECoG) recorded interictal spike activity during sevoflurane and isoflurane anesthesia. We studied 12 patients undergoing insertion of subdural electrodes. Before commencing anesthesia, awake (baseline) EEG recordings were obtained. After inhaled induction, EEG interictal spike activity was evaluated during stable, normocapnic, and hypocapnic (Paco2 = 28-30 mm Hg), sevoflurane anesthesia administered at 1.5 times the minimum alveolar anesthetic concentration (1.5 MAC). Immediately after surgery, ECoG recordings were obtained from subdural electrodes during 1) 1.5 MAC isoflurane, 2) 0.3 MAC isoflurane, and 3) 1.5 MAC sevoflurane anesthesia. EEG spike frequency increased in all patients during sevoflurane anesthesia compared with awake recordings (P = 0.002). Compared with 0.3 MAC isoflurane anesthesia, ECoG interictal spike frequency was higher in all patients during 1.5 MAC sevoflurane anesthesia (P = 0.004) and in 8 of 10 patients during 1.5 MAC isoflurane anesthesia (P = 0.016). Under sufficiently rigorous conditions, both sevoflurane and isoflurane can provoke interictal spike activity at near burst-suppression doses. This property is more prominent with sevoflurane than isoflurane. IMPLICATIONS: The results of this study suggest that the capacity to modulate neuroexcitability is a dose-dependent feature of volatile anesthetics that is manifested most prominently at near burst-suppression doses (i.e., 1.5 times the minimum alveolar anesthetic concentration) and is minimal or absent at low doses.

Patient-controlled sedation using propofol during interventional neuroradiologic procedures.

Patient-controlled sedation (PCS) using propofol has been reported to provide safe and effective sedation during a variety of procedures performed under regional or local anesthesia. In a prospective, randomized fashion, this study evaluated propofol PCS compared to anesthesiologist-administered midazolam-fentanyl sedation during interventional neuroradiologic (INR) procedures. Nineteen patients undergoing 24 INR procedures received propofol PCS (PCS dose, 0.5 mg/kg; lockout interval, 3 min) or anesthesiologist-administered midazolam-fentanyl sedation. Study parameters included discomfort, sedation and anxiety visual analogue scores (VAS), cognitive function, patient satisfaction, and complications. No difference was found between the two sedation techniques with respect to the levels of sedation and anxiolysis. Cognitive function was well preserved in both groups. Patient satisfaction was similarly high in both groups. Complications were similar between groups. These included ventilatory depression (two patients in each group) and excessive sedation (two patients in each group). Three patients in the propofol group became excessively restless, resulting in brief interruptions during the respective procedures. Propofol PCS offers a safe sedation technique during INR procedures with a sedation and anxiolysis profile that was not distinguishable from anesthesiologist-administered midazolam-fentanyl sedation.

Propofol sedation during awake craniotomy for seizures: electrocorticographic and epileptogenic effects.

This prospective study evaluated the effects of propofol sedation on the incidence of intraoperative seizures and the adequacy of electrocorticographic (ECoG) recordings during awake craniotomy performed for the management of refractory epilepsy. Thirty patients scheduled for temporal or frontal lobectomy for epilepsy under bupivacaine scalp block were randomized to receive patient-controlled propofol sedation (PCS) combined with a basal infusion of propofol (n = 15) or neurolept analgesia using an initial bolus dose of fentanyl (0.7 microg/kg) and droperidol (0.04 mg/kg) followed by a fentanyl infusion (n = 15). Propofol administration was suspended 15 min before ECoG recording in the PCS group. The occurrence of inappropriate intraoperative seizures was noted and, based on blind review, the adequacy of ECoG recordings was compared. A higher incidence of intraoperative seizures was noted among the neurolept patients (6 vs 0, P = 0.008). Intraoperatively, ECoG recordings were adequate to proceed with resection in both groups. Evidence of low spike activity on ECoG did not correlate with the type of sedation administered. Higher frequency background ECoG activity was noted among patients who received propofol, but this did not interfere with ECoG interpretation. The use of propofol sedation does not appear to interfere with ECoG during epilepsy surgery, provided administration is suspended at least 15 min before recording.

Propofol sedation during awake craniotomy for seizures: patient-controlled administration versus neurolept analgesia.

This prospective study evaluated the safety and efficacy of patient-controlled sedation (PCS) using propofol during awake seizure surgery performed under bupivacaine scalp blocks. Thirty-seven patients were randomized to receive either propofol PCS combined with a basal infusion of propofol (n = 20) or neurolept analgesia using an initial bolus dose of fentanyl and droperidol followed by a fentanyl infusion (n = 17). Both groups received supplemental fentanyl and dimenhydrinate for intraoperative pain and nausea, respectively. Comparisons were made between groups for sedation, memory, and cognitive function, patient satisfaction, and incidence of complications. Levels of intraoperative sedation and patient satisfaction were similar between groups. Memory and cognitive function were well preserved in both groups. The incidence of transient episodes of ventilatory rate depression (<8 bpm) was more frequent among the propofol patients (5 vs 0, P = 0.04), particularly after supplemental doses of opioid. Intraoperative seizures were more common among the neurolept patients (7 vs 0, P = 0.002). PCS using propofol represents an effective alternative to neurolept analgesia during awake seizure surgery performed in a monitored care environment.

Propofol patient-controlled sedation during hip or knee arthroplasty in elderly patients.

PURPOSE: Little information is available regarding the use of patient-controlled sedation (PCS) among the elderly. This study evaluated the safety and efficacy of propofol PCS among elderly patients undergoing hip or knee arthroplasty. METHODS: Forty patients, aged 65-78 yr, undergoing hip or knee arthroplasty under regional anaesthesia were randomized to receive propofol PCS (dose = 0.3 mg.kg-1, delay = three min; n = 20) or anaesthetist-administered midazolam-fentanyl sedation (n = 20). Sedation, anxiety and discomfort visual analogue scores (VAS) were measured, by an independent observer, preoperatively, immediately at the end of surgery and one hour following admission to the postanaesthetic care unit (PACU). Cognition was evaluated, using an abbreviated Mini Mental Status Examination, preoperatively and in the PACU. Patient satisfaction, based on VAS and a brief questionnaire, was measured in the PACU. The incidence of intraoperative complications was also compared. RESULTS: Patient satisfaction was high in each group. Sedation and anxiety VAS were similar in each group. A high incidence of pain with drug injection was noted among patients receiving propofol (80%). Transient deeper levels of sedation (6 vs 1; P = 0.05) were observed more commonly in the propofol PCS group. CONCLUSION: Propofol PCS provides effective sedation. Using a propofol dose of 0.3 mg.kg-1, transient episodes of deeper sedation were noted more frequently among patients receiving PCS. These episodes did not require intervention but, suggest that this propofol PCS dose approaches the limit of safety and should be further reduced for some elderly patients.

Patient-controlled propofol sedation for elderly patients: safety and patient attitude toward control.

PURPOSE: Little information is available regarding the use of patient-controlled sedation (PCS) among elderly patients undergoing operative procedures under local or regional anaesthesia. This prospective, randomized study evaluated the safety of propofol PCS, and the attitude among elderly patients toward self-administration of sedation during cataract surgery. METHODS: Prospective, randomized study conducted in a University affiliated, tertiary-care hospital. Fifty-five elderly patients (aged 65-79 yr) were randomized to receive propofol patient-controlled sedation (PCS) (n = 28) or no intraoperative sedation (n = 27) during cataract surgery performed under peribulbar block. The PCS parameters consisted of a lockout interval of three minutes and a PCS dose of 0.3 mg.kg-1. Study groups were compared with respect to sedation, anxiety and discomfort visual analogue scores (VAS), cognitive functioning, patient satisfaction and the incidence of intraoperative complications. RESULTS: Patients in the PCS group administered a mean propofol dose of 65 +/- 49 mg during procedures with a mean duration of 46 min. The incidence of intraoperative complications and sedation, anxiety and discomfort VAS were similar between groups. Patient satisfaction with PCS was high. In the PCS group, 10 (35%) of the 28 patients did not use the device because they were comfortable and did not feel they needed sedation. Satisfaction was higher in the PCS group (P = 0.02), whether or not they used the PCS device, compared with patients who did not receive a PCS device. CONCLUSIONS: Propofol PCS represents a safe sedation technique among elderly patients in a monitored care setting. Elderly patients appear to prefer the option of receiving some form of intraoperative sedation and respond favourably to the opportunity to control administration.

Effect of varying intravenous patient-controlled analgesia dose and lockout interval while maintaining a constant hourly maximum dose.

STUDY OBJECTIVE: To investigate the effect on the use of intravenous patient-controlled analgesia (PCA) of varying the dose (D) and lockout interval (LI) while keeping the hourly maximum dose constant. DESIGN: Randomized, prospective study. SETTING: Teaching hospital. PATIENTS: 75 patients scheduled to receive PCA morphine following abdominal surgery. INTERVENTIONS: Postoperatively, patients were randomly assigned to receive PCA morphine with the following parameters: D = 1 mg, LI = 6 min (Group 1-6), D = 1.5 mg, LI = 9 min (Group 1.5-9), or D = 2 mg, LI = 12 min (Group 2-12), so that each group could receive a maximum hourly dose or 10 mg. Inadequate analgesia was managed by increasing the dose and lockout interval, while excessive sedation or respiratory rate less than 10 breaths/min resulted in decreasing the dose and lockout interval. MEASUREMENTS AND MAIN RESULTS: Patients were assessed for pain [visual analog scale (VAS), verbal rating scale (VRS)] and side effects at 1, 2, 4, and 24 hours. The number of doses administered, missed attempts, and morphine used for the first 24 hours was recorded by automatic printout from the PCA machine. There was no difference in the total 24-hour morphine consumption, analgesia, or incidence of side effects among the three groups at any of the measurement times. Two patients, one each in the 1.5-9 and 2-12 groups, required naloxone for respiratory depression. The number of PCA injections, attempts, missed attempts, and the incidence of dosage adjustment were all significantly higher for the 1-6 group (p < 0.05). CONCLUSION: The use of 1.0 mg with a 6-minute lockout may represent appropriate dose titration because this group obtained equivalent analgesia, morphine use, and side effects as the two larger dose and lockout groups. However, the increased number of PCA attempts and missed attempts may reflect lower satisfaction with PCA therapy.

Postoperative cognitive impairment in the elderly. Choice of patient-controlled analgesia opioid.

This study evaluated the safety and cognitive impact of patient-controlled analgesia with fentanyl compared to patient-controlled analgesia with morphine among elderly postoperative patients. In addition, two screening tests for cognitive impairment, the Mini Mental Status Exam and the Short Portable Mental Status Questionnaire, were compared. Ninety-six elderly patients were randomly allocated to receive patient-controlled analgesia with either fentanyl or morphine following hip or knee arthroplasty. Patients were evaluated postoperatively for clinical confusion, cognitive function test results, adequacy of analgesia, drug use and complications. Fentanyl produced less depression in postoperative cognitive function compared to morphine. The incidence of clinical confusion was not statistically different between groups (4.3% for fentanyl versus 14.3% for morphine). Fentanyl patients used more opioid based on a dose ratio of 100:1 suggesting that this dose ratio is inadequate. The incidence of urinary retention was lower in the fentanyl group. A poor agreement between the two tests of cognitive impairment mandates caution when peri-operative cognitive function is compared using different tests.

Anesthesia for intracranial aneurysm surgery.

Aneurysmal rupture represents the most common cause of subarachnoid hemorrhage. Approximately two-thirds of persons who experience a subarachnoid hemorrhage will die or become disabled. Although advances in neurosurgical techniques, neuroanesthetic management, and neuroradiology have resulted in great progress in reducing the operative risk for patients with intracranial aneurysms, the overall outcome following subarachnoid hemorrhage remains disappointing. This article provides an overview of some current concepts related to the perioperative management of patients with intracranial aneurysms, such as the risk and management of rebleeding and vasospasm, and considerations related to the timing of surgery. The anesthetic management of these patients is reviewed, emphasizing principles relating to the facilitation of surgery--by optimizing operative conditions and minimizing the risks of intraoperative aneurysmal rupture or the aggravation of neurologic deficits--and to the provision of a smooth, stable recovery. Despite the disappointing overall prognosis following subarachnoid hemorrhage, adherence to these principles can optimize the outcome for those patients who reach the operating room.

Pulse oximetry compared with Doppler ultrasound for assessment of collateral blood flow to the hand.

Ischaemic injury to the hand after arterial cannulation is a rare but well documented complication and routine testing of the adequacy of collateral circulation is widely advocated. The widespread availability of the pulse oximeter in the operating theatre. its applicability in circumstances where the patient is unable to cooperate, and its dependence on pulsatile blood flow suggest that this device could potentially be usefully applied to the assessment of collateral blood flow. The reliability of the pulse oximeter to detect the presence or absence of collateral circulation was prospectively compared to Doppler ultrasound in 109 hands from 64 adult patients. Nine hands demonstrated inadequate ulnar collateral flow, one hand demonstrated inadequate radial collateral flow and a persistent median artery was found in one hand. In all patients the results of pulse oximeter testing (probe placed on the thumb correlated precisely with the results obtained with the Doppler device (probe located over the lateral aspect of the superficial palmar arch). These results demonstrate pulse oximetry to be a reliable method of assessing collateral blood flow to the hand before arterial cannulation.

Effects of fentanyl, sufentanil, and alfentanil on brain retractor pressure.

Sufentanil and alfentanil have been reported to increase cerebral blood flow and intracranial pressure. Agents producing these effects may adversely affect the relationship between brain retractors and underlying cerebral tissues during craniotomy, potentially predisposing the patient to brain retractor injury. The effects of fentanyl, sufentanil, alfentanil, and a placebo (saline) on brain retractor pressure were therefore evaluated prospectively in 24 adults undergoing elective craniotomy. None of these narcotics significantly affected brain retractor pressure. Each significantly and similarly decreased arterial pressure and cerebral perfusion pressure. If these narcotics are administered in doses that avoid adverse hemodynamic changes that could compromise cerebral tissues indirectly, each of the narcotics studied appears safe for intraoperative administration once the cranium is open.

Postobstructive pulmonary edema following anesthesia.

Pulmonary edema developing after the relief of upper airway obstruction has been reported in association with a diversity of etiologic factors, including hanging, strangulation, tumors, foreign bodies, goiter, and laryngospasm. Since 1977, 18 cases of adults with postobstructive pulmonary edema associated with anesthesia have been reported. A case is presented of a healthy 20-year-old male who developed pulmonary edema following two episodes of acute upper airway obstruction associated with general anesthesia. Postanesthetic laryngospasm has been implicated as the most frequent cause of this syndrome in adults. Risk factors for the development of upper airway obstruction have been identified in the majority of these cases. A heightened awareness among anesthesiologists of this poorly recognized and hence often perplexing syndrome may help reduce the occurrence and facilitate the treatment of this potential complication of perioperative airway management.

A clinical comparison of indices of pulmonary gas exchange with changes in the inspired oxygen concentration.

Several indices have been introduced as convenient alternatives to calculation of the physiological shunt fraction (Qs/QT) for the assessment of pulmonary gas exchange. These include: the arterial-alveolar oxygen tension ratio (a/APO2), the arterial oxygen tension-inspired oxygen concentration ratio (PaO2/FIO2), the respiratory index (RI), [A-a)DO2/PaO2) and the alveolar-arterial oxygen tension difference [A-a)Do2). These indices are in use clinically despite the fact that they may not accurately predict gas exchange in situations where FIO2, Qs/QT or arterial-venous oxygen content is changing. The clinical stability of each of these indices, relative to the behaviour of the physiological shunt, was therefore investigated prospectively in ten mechanically ventilated postoperative adults as FIO2 was varied from 0.30 to 1.00. None of the indices studied reliably reflected the behaviour of the physiological shunt. As FIO2 was increased incrementally from 0.30 to 1.00, 42 to 55 per cent of the measured changes in these indices were opposite in direction to the corresponding changes in the physiological shunt. The maximum magnitudes of the opposite changes were substantial; 24 and 22 per cent for the a/APO2 and PaO2/FIO2 ratio respectively, 67 per cent for the RI and 101 per cent for the (A-a)DO2. We conclude that the use of any of these indices for clinical assessment of a patient's gas exchange defect when FIO2 is varying can be substantially misleading.

The mucopolysaccharidoses and anaesthesia: a report of clinical experience.

Patients with the mucopolysaccharidoses show widespread, progressive involvement and derangement of many organs and tissues which can have profound implications for the anaesthetist. These disorders are uncommon and few anaesthetists care for these patients on a regular basis although individual patients often undergo multiple anaesthetics for procedures intended to improve their quality of life. There is a relative paucity of literature dealing with clinical anaesthetic experience with these patients. We report a retrospective review of the recent experience at the Children's Hospital of Eastern Ontario in Ottawa, Canada, administering 38 anaesthetics to nine patients with several of the mucopolysaccharidoses; specifically the Hunter, Hurler, Sanfilippo and Morquio syndromes. The establishment and maintenance of an adequate airway represents the most commonly encountered anaesthetic-related problem in these patients. We found an overall incidence of airway-related problems of 26 per cent. In patients with the Hurler or Hunter syndromes the incidence of airway-related problems was 53 per cent.