Summary

We do not know how general anaesthetics cause their desired effects. Contrary to what has been thought until relatively recently, the clinical state of anaesthesia consists of multiple components that are mediated via interaction of the anaesthetic drugs with different targets on the molecular, the cellular, the network and the structural–anatomical levels. The mechanisms by which some of these drugs induce the different components of ‘anaesthesia’ may be rather specific: discrete mutations of single amino acids in specific proteins profoundly affect the ability of certain anaesthetics to achieve specific endpoints. Despite this potential specificity, inhalational anaesthetics are present in the body at very high concentrations during surgical anaesthesia. Due to their lipid solubility, general anaesthetics dissolve in every membrane, penetrate into organelles and interact with numerous cellular structures in multiple ways. A priori, it is therefore not unreasonable to assume that these drugs have the potential to cause insidious changes in the body other than those acute and readily apparent ones that we routinely monitor for. Some changes may wane within a short time after removal of the drug (e.g. the suppression of immune cell function). Others may persist after complete removal of the drug and even become self-propagating (e.g. spread of malignant cells, the β-oligomerization of proteins), still others may be irreversible (e.g. the induction of apoptosis in the central nervous system) but of unclear significance. This article will focus on evidence for anaesthetic toxicity in the central nervous system, which appears to be susceptible to anaesthetic neurotoxicity primarily at the extremes of ages but via different pathways: in the neonate, during the period of most intense synaptogenesis, anaesthetics can induce excessive apoptosis; in the aging brain subtle cognitive dysfunction can persist long after clearance of the drug and processes resembling neurodegenerative disorders may be accelerated. At all ages, anaesthetics affect gene expression regulating protein synthesis in poorly understood ways. While it seems reasonable to assume that the vast majority of our patients completely restore homeostasis after general anaesthesia, exposure to these drugs probably has more profound and longer-lasting effects on the brain than heretofore imagined.

Summary

Background and objective: The use of inhalation sedation with sub-anaesthetic concentrations of sevoflurane and nitrous oxide mixture is expected to reduce amounts of intravenous sedative drugs needed to produce a balanced sedation with the benefits of having reduced side-effects. Methods: Eighty-two patients requiring endoscopic and/or surgical procedures under conscious sedation and local anaesthesia were recruited for this pilot study. Conscious sedation was induced with a titrated dose of midazolam and propofol given intravenously until the clinical end-point of conscious sedation was achieved. Subsequently, during the procedure, the patient was asked to breathe sevoflurane 0.1–0.3% and a fixed ratio of 40% nitrous oxide in oxygen given through a face mask. Results: In 78 patients (95.1%), the treatment was completed successfully. Patients were discharged back to the wards within 4–16 min (10.1) without significant side-effects. Treatment was satisfactorily accepted by 38 patients (48.7%) and considered excellent by 40 patients (51.3%). Conclusions: The use of titrated doses of intravenous sedative drugs for induction of conscious sedation followed by the use of low concentrations (0.1–0.3%) of sevoflurane combined with 40% nitrous oxide for maintenance of conscious sedation in patients requiring endoscopic and/or surgical procedures under local anaesthesia, has the potential advantages of reducing amounts of intravenous sedative drugs, less likelihood of problems from drug side-effects and fast recovery and discharge time. Further investigations to establish the technique are currently in progress.

Summary

Background and objective: This study was designed to evaluate early postoperative cognitive recovery after total intravenous anaesthesia with remifentanil–propofol or sufentanil–propofol in patients undergoing craniotomy for supratentorial expanding lesions. Methods: Sixty patients were consecutively enrolled, and randomly assigned to one of two study groups: remifentanil–propofol or sufentanil–propofol anaesthesia. To evaluate cognitive function the Short Orientation Memory Concentration Test (SOMCT) and Rancho Los Amigos Scale (RLAS) were administered to all patients in a double-blind procedure before surgery at 15, 45 min and 3 h after extubation. Results: Mean extubation time was similar in the two groups (13 ± 5 min vs. 19 ± 6 min). A significantly larger number of patients in the remifentanil–propofol group than in the sufentanil–propofol group required antihypertensive medication postoperatively to maintain mean arterial pressure within 20% of baseline (18/30 vs. 4/29; P = 0.0004). Intergroup analysis showed no differences in baseline SOMCT scores (28 ± 1 vs. 28 ± 1) whereas mean SOMCT scores at 15, 45 min and 3 h after extubation were significantly higher in the remifentanil–propofol group (30 patients) than in the sufentanil–propofol group (29 patients) (22 ± 3 vs. 16 ± 3; P < 0.0001 and 27 ± 1 vs. 22 ± 3; P < 0.0001; 28 ± 1 vs. 26 ± 2; P = 0.0126). Conclusions: In conclusion, propofol–remifentanil and propofol–sufentanil are both suitable for fast-track neuroanaesthesia and provide similar intraoperative haemodynamics, awakening and extubation times. Despite a higher risk of treatable postoperative hypertension propofol–remifentanil allows earlier cognitive recovery.

Summary

Background and objective: Enteral acetaminophen (paracetamol) has limited analgesic efficacy due to its delayed absorption and sub-therapeutic plasma concentration. Intravenous (i.v.) acetaminophen solves this issue and could thus provide adequate analgesia as a single agent. We compared intraoperative i.v. acetaminophen with intramuscular (i.m.) meperidine with regard to postoperative analgesia and readiness for discharge in paediatric patients undergoing day care dental restoration. Methods: Forty children were randomized, in this double-blind study, to receive acetaminophen 15 mg kg−1 i.v. (Group A) or meperidine 1 mg kg−1 i.m. (Group M) after anaesthesia induction and before surgery. All patients received midazolam 0.5 mg kg−1 orally 30 min preoperatively and fentanyl 1 μg kg−1 i.v. immediately after induction. Anaesthesia was induced with either sevoflurane inhalation or propofol 3 mg kg−1 i.v. and was maintained with sevoflurane. Postoperatively, the objective pain scale, Ramsay sedation score, and Aldrete score were determined every 5 min until readiness for recovery room discharge (defined as achieving an Aldrete score of 10). Results: Group A had slightly higher pain scores during early recovery compared with Group M (estimated marginal means: 3 ± SEM 0.4 vs. 2 ± SEM 0.4, respectively (95% CI for difference: 0.4, 2.6), P = 0.012 for F-test). In contrast, Ramsay scores were higher in Group M than in Group A during assessment period (estimated marginal means: 4 ± SEM 0.3 vs. 2 ± SEM 0.4, respectively (95% CI for difference: −2.3, −0.3), P = 0.013 for F-test). Group A patients achieved an Aldrete score of 10 sooner than those in Group M (5 ± SEM 2 vs. 16 ± SEM 4 min, respectively (95% CI for difference: −9, −14), P = 0.009). Conclusion: Compared with i.m. meperidine, intraoperative i.v. acetaminophen resulted in slightly higher pain scores but earlier readiness for recovery room discharge in paediatric patients undergoing dental restoration. The potential economic benefit of early recovery room discharge needs to be further explored.

Summary

Background and objective: This study was performed to compare three disposable airway devices, the LMA Unique (LMA-U), the Ambu laryngeal mask (Ambu LM) and the Soft Seal laryngeal mask (Soft Seal LM) for elective general anaesthesia during controlled ventilation in non-paralysed patients. Methods: One hundred and twenty ASA I–III patients scheduled for routine minor obstetric surgery were randomly allocated to the LMA-U (n = 40), Ambu LM (n = 40) or Soft Seal LM (n = 40) groups, respectively. Patients were comparable with respect to weight and airway characteristics. A size 4 LMA was used in all patients and inserted by a single experienced anaesthesiologist. Oxygenation, overall success rate, insertion time, cuff pressure and resulting airway leak pressure were determined as well as a subjective assessment of handling and the incidence of sore throat, dysphagia and hoarseness. Results: Time of insertion was shortest with the Ambu LM, while failure rates were comparable with the LMA-U, the Ambu LM and the Soft Seal LM (median 19 s; range 8–57 s; success rate 100% vs. 14; 8–35; 97% vs. 20; 12–46; 95%). Insertion was judged ‘excellent’ in 75% of patients in the LMA-U group, in 70% of patients in Ambu LM group and in 65% of patients in the Soft Seal LM group. There was no difference between devices with respect to postoperative airway morbidity at 6 h or 24 h following surgery. Conclusions: All three disposable devices were clinically suitable with respect to insertion times, success rates, oxygenation, airway and leak pressures, as well as to subjective handling and postoperative airway morbidity.

Summary

Background and objective: Positive end-expiratory pressure (PEEP) may affect hepato-splanchnic blood flow. We studied whether a PEEP of 10 mbar may negatively influence flow-dependent liver function (indocyanine green plasma disappearance rate, ICG-PDR) and splanchnic microcirculation as estimated by gastric mucosal PCO2 (PRCO2). Methods: In a randomized, controlled clinical study, we enrolled 28 patients after elective cardiac surgery using cardiopulmonary bypass. In 14 patients (13 male, 1 female; age 48–74, mean 63 ± 7 yr) we assessed ICG-PDR and PRCO2 on intensive care unit admission with PEEP 5 mbar, after 2 h with PEEP of 10 mbar and again after 2 h at PEEP 5 mbar. Inspiratory peak pressure was adjusted to maintain normocapnia. Fourteen other patients (8 male, 6 female; age 46–86, mean 68 ± 11 yr) in whom PEEP was 5 mbar throughout served as controls. All patients underwent haemodynamic monitoring by measurement of central venous pressure, left atrial pressure and cardiac index using pulmonary artery thermodilution. Results: While doses of vasoactive drugs and cardiac filling pressures did not change significantly, cardiac index slightly increased in both groups. ICG-PDR remained unchanged either within or between both groups (PEEP10 group: 24.0 ± 6.9, 22.0 ± 7.9 and 25.5 ± 7.7% min−1 vs. controls: 22.0 ± 7.5, 23.8 ± 8.4 and 21.4 ± 6.5% min−1) (P = 0.05). The difference between PRCO2 and end-tidal PCO2 (PCO2-gap) did not change significantly (PEEP10 group: 1.1 ± 0.9, 1.3 ± 0.7 and 1.3 ± 0.9 kPa vs. controls: 0.8 ± 0.5, 0.9 ± 0.5 and 0.9 ± 0.5 kPa). Conclusion: A PEEP of 10 mbar for 2 h does not compromise liver function and gastric mucosal perfusion in patients after cardiac surgery with maintained cardiac output.

Summary

Background and objective: Articaine is an amide local anaesthetic widely used in dentistry. Human ether-a-go-go-related gene (HERG) potassium channels constitute potential targets involved in cardiotoxic side-effects of various pharmacological agents including amide local anaesthetics. The aim of this study was to determine the sensitivity of HERG channels to the inhibitory action of articaine and to further evaluate the effect of the mutations Y652A and F656A in the putative drug-binding region of HERG on the sensitivity for articaine. Methods: We examined the inhibition of wild-type and mutant HERG channels, transiently expressed in Chinese hamster ovary cells by articaine. Whole cell patch-clamp recordings were performed at room temperature. Results: Inhibition of HERG wild-type and HERG Y652A channels by articaine was concentration dependent and reversible. The concentration-response data were described by Hill functions (wild type: IC50 = 224 ± 6 μmol L−1, Hill coefficient h = 1.17 ± 0.03, n = 23; Y652A: IC50 = 360 ± 48 μmol L−1, h = 0.93 ± 0.08, n = 26). The mutation Y5652A decreased the sensitivity by factor 1.6. The mutation F656A decreased inhibition of inward tail currents by 300 μmol L−1 articaine in 100 mmol extracellular K+ 3-fold. Conclusions: Our results indicate that the local anaesthetic articaine does not inhibit HERG channels at clinically relevant concentrations. Articaine may therefore constitute a safer alternative for local and regional anaesthesia. The aromatic amino acid F656 rather than Y652 in the S6 region might play a role in interaction of the drug with the channel.

Summary

Background and objective: Non-steroidal anti-inflammatory drugs are considered as an effective treatment of postoperative pain after laparoscopic cholecystectomy. COX-2 inhibitors are newer drugs having less adverse effects. Data supporting their efficacy postoperatively in comparison to older non-steroidal anti-inflammatory drugs are scarce. Our study is a prospective, randomized, double-blinded, placebo-controlled trial comparing the efficacy of lornoxicam vs. parecoxib for the management of pain after laparoscopic cholecystectomy. Materials and methods: We enrolled 76 patients, ASA I and II, scheduled for elective laparoscopic cholecystectomy. The patients were randomized to receive before induction parecoxib 40 mg i.v., lornoxicam 8 mg i.v. or placebo. Pain at rest and on movement was assessed using a visual analogue scale at 0, 6, 12 h postoperatively. Total meperidine consumption and adverse effects were also recorded. Results: At 12 h, visual analogue scale scores at rest and on movement were significantly lower with parecoxib and lornoxicam compared with control ( P = 0.047). The percentage of patients needing meperidine and the average dose of meperidine administered was significantly lower with parecoxib and lornoxicam compared with control (P < 0.001 and P = 0.018). There was no difference between parecoxib and lornoxicam. One patient receiving lornoxicam vomited. Conclusions: Parecoxib 40 mg i.v. and lornoxicam 8 mg i.v. were equianalgesic and both were more efficacious than placebo for the management of pain after laparoscopic cholecystectomy.

Summary

Background and objective: Tissue Doppler echocardiography is proposed to be a relatively preload independent tool for assessment of diastolic function. No data exist on anaesthetized patients in whom myocardial contractility, vascular tone and baroreceptor reflexes are depressed. The aim of this study was to evaluate the effects of preload alterations on tissue velocities in patients during general anaesthesia for coronary arterial bypass surgery. Methods: Fifteen patients referred for elective aorto-coronary bypass surgery were examined by tissue Doppler echocardiography. Early diastolic velocities in the septal and lateral portion of the mitral annulus were measured during preload interventions induced by tilting of the operating table in patients during general anaesthesia both before surgery and after chest closure. To verify changes in preload we used right atrial pressure and pulmonary artery occlusion pressure. Results: Tissue velocities in both the septal and lateral portion of the mitral annulus were significantly higher when preload was increased, compared to when it was decreased. Alterations in diastolic velocities in the septal portion of the mitral annulus prior to surgery: 0.8 ± 0.2 cm s−1, P < 0.001, after surgery: 1.1 ± 0.2 cm s−1, P < 0.001. Alterations in diastolic velocities in the lateral portion of the mitral annulus prior to surgery: 1.4 ± 0.2 cm s−1, P < 0.001, after surgery: 1.1 ± 0.3 cm s−1, P < 0.01. Concomitant changes in right atrial pressure and pulmonary artery occlusion pressure were 11 ± 1 and 12 ± 1 mmHg before surgery and 13 ± 1 and 12 ± 1 mmHg after surgery (P < 0.001 for all), respectively. Conclusion: These results show that tissue velocities of the mitral annulus are preload dependent in patients during general anaesthesia both before and after coronary surgery.

Summary

Background and objective: Postoperative nausea and vomiting (PONV) after ophthalmic surgery under general anaesthesia remains a complex and perturbing complication associated with several factors. Little information is available regarding the risk factors for nausea and vomiting after vitrectomy in adults. In this study, we evaluated the potential risk factors for PONV after vitrectomy in adult patients. Methods: Univariate and multivariate analyses of clinical factors associated with PONV were undertaken in a retrospective case–control series of 247 adult patients undergoing vitrectomy under general anaesthesia. We examined PONV for the first 48 h. Factors examined were age, body mass index (BMI), smoking status, H2-blocker as premedication, type of general anaesthesia (sevoflurane and fentanyl or total intravenous (i.v.) anaesthesia with propofol and fentanyl), duration of surgery, and intraoperative fentanyl dose. Results: Fifty-nine patients (24%) reported one or more episodes of PONV during the study period. Female gender (P < 0.01), lower BMI (P < 0.01) and general anaesthesia with inhalational anaesthetics (P < 0.01) were significantly related to nausea during the first 2 h postoperatively. Female gender (P < 0.01) was significantly related to nausea and vomiting throughout the study period. Other factors, including smoking status, did not alter the risk for nausea and/or vomiting. Conclusions: We conclude that female gender, lower BMI and inhalation anaesthesia are the main risk factors for PONV after vitrectomy in adults. Smoking status did not reduce the incidence of PONV in our patients.

Summary

Background and objective: Ondansetron is widely used for the prophylaxis of postoperative nausea and vomiting, while haloperidol is an antiemetic that lacks recent data on efficacy and adverse effects. Methods: In this prospective, randomized, double-blinded study involving 93 females undergoing gynaecological procedures under general anaesthesia, we compared the efficacy and adverse effects of prophylactic haloperidol 1 mg intravenous and ondansetron 4 mg intravenous vs. placebo. Results: During the overall observation period (0–24 h), in the haloperidol, ondansetron and placebo groups respectively, the incidence of nausea and/or vomiting was 40.7% (11/27), 48.2% (13/27) and 55.5% (15/27), and the need of rescue antiemetics was 22.2% (6/27), 44.4% (12/27) and 40.7% (11/27), with P values >0.05 among the three groups. During the early observation period (0–2 h), in the haloperidol, ondansetron and placebo groups respectively, the incidence of nausea and/or vomiting was 13.7% (4/29), 26.6% (8/30) and 43% (13/30), and the need for rescue antiemetics was 6.8% (2/29), 26.6% (8/30) and 36.6% (11/30). Between haloperidol and placebo groups, the P value was 0.04 for nausea and/or vomiting, and was 0.01 for rescue antiemetics, in addition to lower nausea scores (P = 0.03). During the late observation period (2–24 h), no significant difference was shown among the three groups. Conclusion: The prophylactic administration of 1 mg intravenous haloperidol or 4 mg ondansetron, in female patients undergoing gynaecological surgery, did not improve the overall incidence of nausea and/or vomiting vs. placebo. However, haloperidol 1 mg proved to be an effective antiemetic in the early observation period without significant adverse effects.

Summary

Background and objective: It is widely accepted that sevoflurane affects cerebral circulation, but there are uncertainities regarding the magnitude of its effect. The aim of the present work was to assess the effect of sevoflurane on the cerebral circulation at surgical levels of anaesthesia. Methods: Twenty patients undergoing elective lumbar discectomies were investigated. Anaesthesia was induced with propofol and maintained with sevoflurane. The level of surgical anaesthesia was determined by bispectral index, the target level was 45–55. Transcranial Doppler (TCD) measurement was performed before induction and after reaching the surgical level of anaesthesia. Besides routine parameters (middle cerebral artery mean blood flow velocity (MCAV) and pulsatility index (PI)) derived parameters (estimated cerebral perfusion pressure (eCPP), cerebral blood flow index (CBFI) and resistance area product (RAP)) were calculated by taking changes of mean arterial pressure also into account. Results: MCAV decreased from 54.1 ± 13.3 to 43.7 ± 18.5 cm s−1, P < 0.01 and PI increased from 0.79 ± 0.2 to 0.92 ± 0.2, P < 0.01 after reaching the surgical level of anaesthesia. As a result eCPP decreased by 18.2%, CBFI by 25.5% and RAP increased by 15% respectively. Conclusions: Our data indicate a vasodilatory effect of sevoflurane at surgical level of anaesthesia on large cerebral vessels or a vasoconstriction of the resistance arterioles likely caused by decreased brain metabolism.

Summary

Background and objective: Extremity surgery with tourniquet to provide a bloodless field may be a good human model for ischaemia reperfusion (IR) injury. The aim of this study was to investigate the effects of three different modes of propofol use on tourniquet induced IR injury in lower extremity operations. Methods: Thirty-three consecutive ASA Grade I and II patients were randomized into three groups of 11 patients each. In the spinal group (Group S), after intrathecal anaesthesia, sedation was given with a propofol infusion at 2 mg kg−1 h−1 after a 0.2 mg kg−1 bolus dose and fentanyl 100 μg. In the general (Group G) and TIVA (Group T) groups, general anaesthesia was induced with propofol 2 mg kg−1 with fentanyl 100 μg and maintained with inhalation of halothane or infusion of propofol respectively. Venous blood samples were obtained at different time points for measurements of plasma malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) levels. Results: Plasma MDA levels were increased significantly in the Group G at 1 min before tourniquet release and 5 and 20 min after tourniquet release compared with before induction of general anaesthesia (baseline). Before intrathecal anaesthesia and before induction of general anaesthesia significantly decreased levels of MDA were observed both before and after tourniquet release compared to baseline. Plasma SOD and CAT concentrations were decreased significantly only at tourniquet release in the Group G compared with baseline. In the Groups S and T these enzymes were not changed significantly. Plasma GPx levels were not altered in any groups. Conclusion: Propofol administration may inhibit lipid peroxidation and restore antioxidant enzyme levels in extremity surgery requiring tourniquet application.

Summary

Background and objective: To compare the inotropic and lusitropic effect of lidocaine and mepivacaine on rat papillary muscle. Methods: Effects of lidocaine and mepivacaine (10−8−10−3 M) were studied in rat left ventricular papillary muscles in vitro at a calcium concentration of 1 mmol, under low (isotony) and high (isometric) loads. Results: Lidocaine induced a significant negative inotropic effect in isotonic and isometric conditions whereas mepivacaine did not. Mepivacaine only induced a negative inotropic effect when added as a bolus for the highest concentration and this effect was significantly more pronounced with lidocaine than with mepivacaine (active force at 10−3 M: 63 ± 10 vs. 84 ± 10% of baseline, P < 0.05). Increasing calcium concentration resulted in a greater positive inotropic effect in the control (199 ± 11% of baseline) and mepivacaine groups (197 ± 22% of baseline) when compared to the lidocaine group (163 ± 19% of baseline, P < 0.05 vs. lidocaine and control groups), suggesting an impairment on intracellular Ca2+ handling by lidocaine. A negative lusitropic effect under low load was observed only for mepivacaine and suggested an impairment of sarcoplasmic reticulum function. Lidocaine and mepivacaine did not modify postrest potentiation but significantly depressed the force–frequency relationship. Conclusions: The negative inotropic and lusitropic effects induced by lidocaine were more important than that of mepivacaine and may involve an impairment of intracellular Ca2+ handling.