Effect of anaesthetic technique on oestrogen receptor-negative breast cancer cell function in vitro.

BACKGROUND: Metastatic recurrence is the main cause of breast cancer-related deaths. Tumour cell proliferation and migration are crucial steps in the metastatic process. Several perioperative factors, including general anaesthesia and opioid analgesia, adversely affect immune function, potentially increasing metastatic recurrence. Regional anaesthesia-analgesia has been consistently shown to attenuate the stress response to surgery, and also reduce opioid and general anaesthesia requirements, thereby attenuating this perioperative immunosuppression. We investigated the effect of serum from breast cancer surgery patients who received different anaesthetic techniques on breast cancer cell function in vitro. METHODS: Patients were randomized to receive propofol/paravertebral anaesthesia-analgesia (propofol/paravertebral, n=11) or sevoflurane general anaesthesia with opioid analgesia (sevoflurane/opioid, n=11). The ER-negative MDA-MB-231 cell line was treated with patient serum from both groups. The effects on proliferation and migration were measured. RESULTS: Treatment groups were well balanced for age, weight, surgical procedure, and cancer pathology. Pain scores were lower at 1 and 2 h in the propofol/paravertebral analgesia group. Compared with preoperative values, proliferation of MDA-MB-231 cells treated with postoperative patient serum at 10% concentration from the propofol/paravertebral group was significantly reduced compared with the sevoflurane/opioid group (-24% vs 73%, P=0.01). There was no significant change in MDA-MB-231 cell migration after treatment with patient serum between the two groups. CONCLUSIONS: Serum from patients receiving propofol/paravertebral anaesthesia for breast cancer surgery inhibited proliferation, but not migration, of ER-MDA-MB-231 cells in vitro, to a greater extent than that from patients receiving sevoflurane/opioid anaesthesia-analgesia. This implies that anaesthetic technique alters the serum molecular milieu in ways that may affect breast cancer cell function, possibly by altering anaesthetic and opioid drug administration and resultant pain scores.

Cardiorespiratory effects of laparoscopy with and without gas insufflation.

BACKGROUND: Patients who are undergoing laparoscopic procedures can present with a number of ventilatory and circulatory problems. The use of a gasless technique for performing a laparoscopy by using a mechanical lifting device may potentially avoid such problems. OBJECTIVE: To compare the cardiorespiratory effects of laparoscopy with and without gas insufflation. METHODS: Twelve adult pigs were randomized to undergo a laparoscopy by using either carbon dioxide insufflation or mechanical elevation. Full invasive monitoring was performed preoperatively and at 10-minute intervals throughout the operative period. Parameters that were measured included blood gas determinations, mean arterial pressure, pulmonary arterial pressure, pulmonary capillary wedge pressure, central venous pressure, cardiac output, stroke volume, and total peripheral resistance. RESULTS: Carbon dioxide insufflation unlike mechanical elevation led to a fall in PO2 and absorption of a significant quantity of CO2, resulting in hypercapnia, acidosis, and a consequent hyperdynamic circulation. CONCLUSION: These findings have significant implications for the use of CO2 insufflation for laparoscopy in patients with a compromised respiratory or cardiac status.

Antiproliferative actions of inhalational anesthetics: comparisons to the valproate teratogen.

The antiproliferative potential of the volatile anesthetics isoflurane, enflurane and sevoflurane was determined and compared to the valproate teratogen. The in vitro system employed, a G1 phase proliferative arrest endpoint in C6 glioma, has served previously to discriminate agents with known teratogenic potential in vivo. Based on estimated IC(50) values that were within twice the estimated minimum aveolar concentration value, the rank antiproliferative potency of the inhalational anesthetics employed was isoflurane=enflurane>>sevoflurane. Flow cytometric analysis of growth-arrested cell populations failed to reveal specific accumulation in any cell cycle phase and the lack of a G1 phase-specific effect was confirmed by the absence of a transient, time-dependent sialylation event in synchronized cells. The antiproliferative mechanism of volatile anesthetics, and valproate, was mediated at hydrophobic binding sites, as increasing the hydration sphere of the drug-micelle complex, using the hygroscopic qualities of the dimethylsulfoxide vehicle, completely reversed this effect. Our findings suggest inhalational anesthetics lack the specific in vitro characteristics of the valproate teratogen.

Pulmonary embolism following tonsillectomy.

Acute post-operative pulmonary embolism is a serious potentially life-threatening complication which is not anticipated in young patients undergoing non-major surgery. We report a case in which a 32-year-old previously healthy woman developed a major pulmonary embolism following tonsillectomy. Subsequent investigations revealed the presence of an occult malignancy. This case highlights the role of paraneoplastic hypercoagulable states in the aetiology of venous thromboembolism and the importance of thromboprophylaxis in the presence of confirmed or suspected malignancy. To our knowledge no case of major pulmonary embolism occurring after tonsillectomy has been previously reported.

Effects of the combination of halothane and serotonin uptake blockers on synaptic transmission in the rat dentate gyrus in vitro.

Although the exact basis of their action remains unknown, volatile agents affect noradrenergic and serotoninergic systems. Imipramine and fluoxetine have documented effects on these neurotransmitter transmission systems. Given the common sites of action of these antidepressants and halothane, we examined their individual and combined effects on tonic excitatory post-synaptic potentials (EPSPs) and frequency dependent blockade in the rat dentate gyrus in vitro. Extracellular recordings of field EPSPs were maintained from the dentate gyrus, in the presence of picrotoxin (100 microM). Stimulation at 30 Hz (200 ms) allowed investigation of frequency dependent blockade. Once a stable equilibrium was established, halothane, imipramine and fluoxetine were administered via the perfusate and recordings were made. Halothane produced a dose dependent reduction in EPSP amplitude (EC50 0.28 mM; n = 12). Imipramine (1-10 microM) potentiated the EPSP amplitude (148.2 +/- 8.2%; imipramine 1 microM; n = 6). Fluoxetine (0.5-10 microM) reduced EPSP amplitude to 83.7 +/- 22.1% of control (n = 6). In the presence of halothane 0.2 mM, imipramine reduced the EPSP amplitude to 56.5 +/- 9.9% of control (imipramine 10 microM; n = 6; p < 0.05 compared with imipramine alone). Halothane (0.2 mM) demonstrated frequency dependent blockade. However, neither imipramine nor fluoxetine showed use dependent inhibition at the doses investigated. When combined with halothane 0.2 mM, fluoxetine 10 microM demonstrated frequency dependent blockade at the sixth pulse in the train compared with controls (13.8 +/- 4.7% vs 38.1 +/- 8.3%; n = 6; p < 0.05). The halothane-imipramine combination did not exhibit use dependent blockade greater than controls. The reversal of imipramine-induced EPSP potentiation by the preapplication of halothane has not been previously reported. It may be due to modulation of noradrenergic transmission by halothane. The frequency dependent blockade produced by the combination of fluoxetine 10 microM and halothane may be mediated by a nonspecific membrane effect on 5-HT uptake. These differing effects underline the broad action of volatile agents on synaptic mechanisms.

Anaesthesia for non-cardiac surgery in the post-cardiac transplant patient.

As survival and quality of life continue to improve for cardiac transplant recipients, the number of patients with functioning heart transplants who present for surgery continues to increase. The conditions for which surgery may be required, the specific problems relating to anaesthesia and the necessary measures which should be taken to ensure an uncomplicated clinical course are discussed. A clear understanding of the physiology and pharmacology of the denervated heart is essential for these patients to undergo safely anaesthesia and surgery.

Elective tracheal intubation in cervical spine injuries.

Patients presenting for surgical stabilisation of an unstable cervical spine are at risk of sustaining a further iatrogenic spinal cord injury during intubation of the trachea. Controversy exists regarding the optimal anaesthetic technique for securing the airway. We reviewed the techniques employed for intubating the trachea in our hospital over a five year period. Tracheal intubation was achieved using two different techniques: awake fibre-optic intubation with local anaesthesia, and general anaesthesia via the intravenous or inhalational route with neuromuscular blockade. Forty five patients were included. 16 patients demonstrated a pre-operative neurological deficit. Awake fibre-optic intubation was used in 27 cases, general anaesthesia was employed via the intravenous route in 17 cases and the inhalational route in 1 case. Weighted traction was employed in all cases to immobilize the cervical spine during intubation. There was no new neurological sequelae with any of these techniques. Our study suggests that there is no optimal anaesthetic technique for intubating the trachea in patients with cervical spine injuries and it is noteworthy that in line traction was used in every case.

Fentanyl and clonidine as adjunctive analgesics with levobupivacaine in paravertebral analgesia for breast surgery.

The addition of fentanyl or clonidine to levobupivacaine was evaluated in patients undergoing breast surgery under general anaesthesia with intra- and postoperative paravertebral analgesia. Patients were randomly allocated to four groups: Group L received 19 ml bolus levobupivacaine 0.25% plus 1 ml saline followed by an infusion of levobupivacaine 0.1%; Group LF received 19 ml bolus levobupivacaine 0.25% plus fentanyl 50 microg followed by an infusion of levobupivacaine 0.05% with fentanyl 4 microg x ml(-1); Group LC received 19 ml bolus levobupivacaine 0.25% plus clonidine 150 microg followed by an infusion of levobupivacaine 0.05% with clonidine 3 microg x ml(-1); Group C (control) received general anaesthesia without paravertebral analgesia. All groups received postoperative i.v. morphine patient controlled analgesia (PCA). Although mean (SD) postoperative PCA morphine consumption was decreased in LF [7.9 (4.1) mg] and LC [5.9 (3.5) mg]vs L [27.7 (8.6) mg] or C patients [21.7 (5.5) mg], p < 0.01, paravertebral fentanyl and clonidine were associated with significantly increased vomiting and hypotension, respectively.

Inhibition of the stress response to breast cancer surgery by regional anesthesia and analgesia does not affect vascular endothelial growth factor and prostaglandin E2.

Angiogenesis is essential for breast cancer metastases formation and is mediated by vascular endothelial growth factor (VEGF) and prostaglandin E2 (PGE2). We hypothesized that serum levels of VEGF and PGE2 are increased by the stress response to breast cancer surgery and attenuated by paravertebral anesthesia and analgesia (PVAA). Thirty women undergoing mastectomy were enrolled in this prospective, randomized study, to receive general anesthesia (GA) and postoperative opioid analgesia (morphine 0.1 mg/kg bolus and patient-controlled infusion) or GA and PVAA (72-h infusion). All patients received rectal diclofenac. Venous blood samples were taken preoperatively and at 4 and 24 h postoperatively for serum glucose, cortisol, C-reactive protein, VEGF, and PGE2. PVAA inhibited the surgical stress response, as indicated by significantly less plasma glucose, cortisol, and C-reactive protein. VEGF and PGE2 values did not differ significantly between the groups. Mean (SD) percentage change in VEGF at 4 and 24 h respectively were 3% +/- 44% versus 9% +/- 80%, P=0.29 and 5% +/- 43% versus -10% +/- 63%, P=0.41 for patients with combined general and PVAA and GA alone, respectively. Mean percentage change in postoperative PGE2 at 4 and 24 h respectively was 10% +/- 17% versus 11% +/- 69%, P=0.29 and 34% +/- 19% versus 47% +/- 18%, P=0.15. We conclude that despite inhibiting the surgical stress response, PVAA had no effect on serum levels of putative breast cancer angiogenic factors, VEGF and PGE2.

Intrathecal morphine in the management of pain following cardiac surgery. A comparison with morphine i.v.

Forty-four patients undergoing coronary revascularization received either intrathecal morphine 1 mg (n = 15), intrathecal morphine 2 mg (n = 15), or i.v. morphine 30 mg (n = 14) after the induction of anaesthesia. Morphine 2.5 mg i.v. was given, as required, in the postoperative period and pain score, respiratory rate and PaCO2 measured every 2 h. FVC, FEV1 and PEFR were measured before, and 24 h after, the induction of anaesthesia. Mean overall pain scores in both intrathecal groups were significantly lower than in the i.v. group (P less than 0.01), but did not differ significantly between the intrathecal groups. Consumption of supplementary morphine was significantly lower in both intrathecal groups (P less than 0.01). Mean PaCO2 was significantly higher in patients given intrathecal morphine 2 mg. This was significant at 12, 14 and 16 h after induction of anaesthesia. Respiratory rate did not differ significantly between the groups. Postoperative PEFR was significantly better in patients given intrathecal morphine (P less than 0.01). These results suggest that intrathecal morphine provided better analgesia after cardiac surgery than did a conventional regimen. The lower dose (1 mg) was associated with less respiratory depression as assessed by PaCO2 measurements.

Laryngeal mask airway positioning is related to Mallampati grading in adults.

The Mallampati classification is a commonly used means of preoperatively predicting a difficult endotracheal intubation. As the laryngeal portion of the laryngeal mask airway (LMA) must sit over the larynx, we wondered whether the Mallampati classification also predicts difficulty in achieving adequate seating of the LMA. LMA positioning was assessed prospectively in 100 adult patients by fiberoptic bronchoscopy to determine whether there was a relationship between the ease of seating of the LMA and the Mallampati classification. In 72 patients, optimal seating of the LMA was achieved on the first attempt at insertion, and all these patients were classified as Mallampati class 1 or 2. In all 28 cases of difficulty with LMA insertion, the patients were Mallampati class 2 or 3. In two cases the LMA was abandoned, and in these cases both patients were Mallampati class 3, (P = 0.0001 by chi 2 analysis). We conclude that the Mallampati classification indicates difficulty not only in tracheal intubation but also in achieving an adequate airway with the LMA.

Intrathecal morphine: one year's experience in cardiac surgical patients.

OBJECTIVES: This study was designed to assess the benefits and complications associated with the use of intrathecal morphine (ITM) in patients undergoing coronary artery bypass surgery (CABG). DESIGN: This was a retrospective chart review. SETTING: The study was performed in a single hospital that is affiliated with a university medical school. PARTICIPANTS: The charts of all patients who presented for CABG in a 12-month period were reviewed. INTERVENTIONS: All patients entered into the study had received ITM (0.03 mg/kg) at induction of anesthesia. MEASUREMENTS AND MAIN RESULTS: Complete data were available for 152 patients (86%). Median duration of ventilation postoperatively was 12 hours, and median duration of stay in the ICU was 72 hours. All patients received additional postoperative opioid analgesia, many by the epidural route. Fifteen percent developed respiratory complications, and the incidence of respiratory depression was 1.9%. Thirty-five percent required inotropic support; 17% percent were treated for hypertension; and 49% received antiarrhythmic therapy. The re-infarction rate was 2.6%, and 3% developed cardiac tamponade. Three patients developed neurologic complications unrelated to lumbar puncture. There were no in-hospital deaths. CONCLUSIONS: ITM is safe and provides effective pain relief after cardiac surgery. The high incidence of respiratory depression confirms the need for close observation of these patients postoperatively.

Anaesthetic depth at induction. An evaluation using clinical eye signs and EEG polysomnography.

We describe the stages of non-REM sleep induced by anaesthesia with sevoflurane 8% in oxygen and relate these stages to clinical eye positions. We explored John Snow's observation (1847) that 'when voluntary movement ceases, with the eyes fixed in an upward gaze during the gas induction of anaesthesia, the patient is protected against the risk of mental suffering' (awareness). Unpremedicated ASA 1 patients undergoing elective tonsillectomy were studied using EEG polysomnographic principles and clinical eye movement tracking. The results expressed as median and range were: latency to stage 1 sleep 4.5 min [2.5-7.5], stage 2 sleep 5 min [3.5-8.5], stage 3 sleep 5.5 min [4-12] and stage 4 sleep 6 min [4.5-15.5]. Eye position 5, the point of no further eye movement, was reached after 9 min [5.5-18.5]. This was significantly longer than the time taken to reach the stage 4 sleep EEG, p < 0.01, supporting Snow's observation and encouraging investigation into eye movement tracking technology as a potential monitor of anaesthetic depth.

Evidence for analgesia mediated by peripheral opioid receptors in inflamed synovial tissue.

Intra-articular morphine (5 mg in 25 ml) was administered to patients for post-operative analgesia following arthroscopic knee surgery. At various time intervals, 30 min to 4 h post morphine, venous blood samples were taken in order to determine plasma levels of morphine and its primary metabolites, morphine-3-glucuronide and morphine-6-glucuronide. Measurable amounts of morphine and morphine-3-glucuronide were found in the plasma of 7/10 patients whereas morphine-6-glucuronide was detected in only 2/10 patients. The plasma levels of morphine were lower than that regarded sufficient for post-operative analgesia in all but two patients, indicating a possibility of peripheral analgesia. In addition, synovial biopsy samples were assayed for the presence of opioid binding sites. Tissue samples from 11 different patients were analysed and 6/11 exhibited specific binding of [3H]naloxone, indicating the presence of opioid binding sites/receptors. The receptor type (i.e. mu-, delta- or k-) is at present unknown. Taken together, these data provide evidence that locally administered opiates can act on specific opioid receptors in the synovium to mediate analgesia.

The laryngeal mask airway reduces blood flow in the common carotid artery bulb.

PURPOSE: The introduction of the laryngeal mask airway (LMA) has had a major impact on anaesthetic practice in the last ten years. Previous authors have demonstrated pressures equivalent to mean arterial blood pressure within the cuff of the LMA. This study examined the effects of cuff inflation on the cross sectional area, flow and velocity of blood flow at the level of the carotid sinus. METHODS: Seventeen patients scheduled to have LMAs inserted as part of routine anaesthetic management were recruited into the study. Measurements of the common carotid artery bulb area, peak velocity and blood flow were performed upon LMA cuff inflation and deflation using a 5 MHz pulse wave Doppler probe. RESULTS: Deflation of the cuff resulted in an increase in the cross sectional area (from 0.58 +/- 0.05 to 0.64 +/- 0.04 cm2; P < 0.005), an increase in blood flow (from 65.6 +/- 5.6 to 73.9 +/- 5.6 cm3.sec-1; P < 0.05) and a slight but non significant increase in velocity of blood flow. CONCLUSION: This study demonstrates that inflation of the cuff on the LMA results in a decrease in carotid bulb cross sectional area which results in a decrease in blood flow.

The effect of rectal diclofenac on pruritus in patients receiving intrathecal morphine.

In this prospective randomised study, pruritus and pain were evaluated in patients undergoing abdominal surgery in which intrathecal morphine was administered. Each patient received intrathecal morphine 0.3 mg prior to induction, followed by a standard anaesthetic. The patients were randomly allocated to one of two groups. One group received 100 mg of rectal diclofenac immediately post-induction. Patients receiving diclofenac had significantly lower pruritus scores at 30 min (p = 0.0076), 2, 4, 8 and 24 h postoperatively, as well as significantly reduced pain scores at each time point (p < 0.0001 at each study interval). Morphine consumption in the first 24 h was also significantly lower in this group. In conclusion, rectal administration of diclofenac significantly reduces the incidence and severity of postoperative pruritus. It also significantly reduces pain and further analgesic requirements postoperatively.