Summary

Background and objective: The aim was to train artificial neural nets to predict the recovery of a neuromuscular block during general anaesthesia. It was assumed that the initial/early neuromuscular recovery data with the simultaneously measured physical variables as inputs into a well-trained back-propagation neural net would enable the net to predict a rough estimate of the remaining recovery time.

Methods: Spontaneous recovery from neuromuscular block (electrically evoked electromyographic train-of-four responses) were recorded with the following variables known to affect the block: multiple minimum alveolar concentration, end-tidal CO2 concentration, and peripheral and central temperature.

Results: The mean prediction errors, mean absolute prediction errors, root-mean-squared prediction errors and correlation coefficients of all the nets were significantly better than those of average-based predictions used in the study. The root-mean-squared prediction error of the net – employing minimum alveolar concentrations from the whole recovery period (the recovery time from E2/E1 = 0.30 to E4/E1 = 0.75; E1 = first response of train-of-four, E2 = second response of train-of-four, etc.) – were significantly smaller than those of other nets, or the same net employing minimum alveolar concentrations only from the initial recovery period (from E2/E1 = 0.30 to E4/E1 = 0.25).

Conclusions: Neural nets could predict individual recovery times from the neuromuscular block significantly better than the average-based method used here, which was supposed to be more accurate than guesses by any clinician. The minimum alveolar concentration was the only monitored variable that influenced the recovery rate, but it did not aid neural net prediction.

Summary

Background and objective: General anaesthesia may contribute to postoperative cognitive decline in the elderly. The aim was to determine the effects of repeated pentobarbital anaesthesia throughout life on central cholinergic function in the rat.

Methods: Young Lewis rats were randomly allocated to two groups. The anaesthesia group (n = 15) was anaesthetized with pentobarbital 20 mg kg−1 intraperitoneally at 6, 8.5, 11, 13.5, 16, 18.5, 21 and 23.5 months of age. The control group (n = 12) was treated identically, apart from the anaesthesia. At 26 months of age, the animals were killed and the brain dissected and stored for analysis. Central cholinergic function in the cortex and hippocampus was assessed by measuring [3H]-epibatidine and [125I]α-bungarotoxin binding to nicotinic receptors and choline acetyltransferase (ChAT) activity.

Results: Tissue from nine rats in the anaesthesia group and eight in the control group was available for analysis. There was a significant reduction in α-bungarotoxin binding in the anaesthetized compared with the control group in the superior cortex (P < 0.0002) and molecular cortex (P < 0.04). There were no significant differences between the groups for epibatidine binding or ChAT.

Conclusions: Repeated anaesthesia in rat reduces central nicotinic cholinergic binding in the cortex. The findings may have implications for postoperative cognitive function studies.

Summary

Background and objective: The effects of xenon on mesenteric vascular resistance have not been investigated. Because human beings anaesthetized with xenon show good cardiovascular stability, we believed that the agent would have little or no effect on vascular resistance in the splanchnic bed. We determined the effects of different inhaled xenon concentrations on mesenteric blood flow and mesenteric oxygen consumption in pigs sedated with intravenous propofol.

Methods: Twenty-three minipigs were instrumented with transit time flow probes around the pulmonary and superior mesenteric arteries as well as with pulmonary artery and portal venous catheters. A 14 h recovery was allowed followed by recordings of baseline values. Xenon was then randomly administered in 0.30, 0.50, and 0.70 end-tidal fractions.

Results: The administration of xenon resulted in an 8% (not dose dependent) decrease in mean arterial pressure (from 99 ± 15 to 91 ± 19 mmHg; P < 0.05), a 20% decrease in calculated systemic oxygen consumption (from 0.23 ± 0.07 to 0.19 ± 0.04 L min−1; P < 0.01), a 20% reduction in mesenteric oxygen delivery (from 41 ± 12 to 33 ± 11 mL min−1; P < 0.001), a 37% reduction in mesenteric metabolic rate of oxygen (from 11.3 ± 3.6 to 7.1 ± 3.2 mL min−1; P < 0.01) and an 8% decrease in mesenteric artery blood flow (0.22 ± 0.07 to 0.20 ± 0.07 L min−1; P < 0.05) in a dose-dependent fashion. Heart rate, cardiac output, systemic vascular resistance, mesenteric vascular resistance, mesenteric oxygen extraction fraction and portal lactate concentration were not significantly altered by xenon.

Conclusions: Xenon inhalation in the propofol-sedated pig had no measurable effects on mesenteric vascular resistance. This finding may partly explain the well-known cardiovascular stability observed in patients anaesthetized with xenon. Although mesenteric artery blood flow and mesenteric oxygen delivery decreased during xenon administration, unchanged mesenteric oxygen extraction fraction and portal lactate suggest that metabolic regulation of the splanchnic circulation remained unaltered.

Summary

Background and objective: Neutrophils are important both for the immunological defence system and for the inflammatory tissue autoinjury mechanism. However, many local anaesthetics impair certain neutrophil functions. The aim was to assess the effects of ropivacaine, bupivacaine and lidocaine on human neutrophils from adult volunteers.

Methods: Chemotaxis, phagocytosis, reactive oxygen species production, intracellular calcium ion ([Ca2+]i) concentrations and protein kinase C activity were measured in the absence and presence of ropivacaine, bupivacaine or lidocaine. The lowest concentrations of the local anaesthetics were similar to those clinically observed in the plasma.

Results: Bupivacaine did not affect any neutrophil function (P > 0.05). Ropivacaine failed to change chemotaxis or phagocytosis, while lidocaine suppressed both these neutrophil functions. Ropivacaine (15, 150 μg mL−1) and lidocaine (20, 200 μg mL−1) impaired neutrophil production of O2−, H2O2 and OH− (P < 0.05) at similar rates (by 7–10%). These same concentrations of ropivacaine and lidocaine suppressed [Ca2+]i elevation. Finally, neither ropivacaine nor bupivacaine inhibited protein kinase C activity, while lidocaine did.

Conclusions: Suppression of the [Ca2+]i response in neutrophils by ropivacaine may represent one of the mechanisms responsible for the impairment of neutrophil functions. It should be emphasized that the inhibitory effects of ropivacaine are minor and are attained only at high concentrations, which may minimize the clinical implication of ropivacaine-associated impairment of reactive oxygen species production. Further studies using in vivo systems are required to identify the inhibitory effects of ropivacaine on reactive oxygen species production in clinical settings.

Summary

Background and objective: Both chronic occupational exposure to volatile anaesthetic agents and acute in vitro exposure of neutrophils to isoflurane have been shown to inhibit the rate of apoptosis of human neutrophils. It is possible that inhibition of neutrophil apoptosis arises through delaying mitochondrial membrane potential collapse. We assessed mitochondrial depolarization and apoptosis in unexposed neutrophils and neutrophils exposed to sevoflurane in vivo.

Methods: A total of 20 mL venous blood was withdrawn pre- and postinduction of anaesthesia, the neutrophils isolated and maintained in culture. At 1, 12 and 24 h in culture, the percentage of neutrophil apoptosis was assessed by dual staining with annexin V-FITC and propidium iodide. Mitochondrial depolarization was measured using the dual emission styryl dye JC-1.

Results: Apoptosis was significantly inhibited in neutrophils exposed to sevoflurane in vivo at 24 (exposed: 38 (12)% versus control: 28 (11)%, P = 0.001), but not at 1 or 12 h, in culture. Mitochondrial depolarization was not delayed in neutrophils exposed to sevoflurane.

Conclusions: The most important findings are that sevoflurane inhibits neutrophil apoptosis in vivo and that inhibition is not mediated primarily by an effect on mitochondrial depolarization.

Summary

Background and objective: Little is known about the interaction of newer volatile anaesthetics with endothelial eicosanoid production. Sevoflurane may possibly reduce prostacyclin formation. Thus, we compared the influences of sevoflurane and isoflurane on endothelial prostacyclin production.

Methods: Production of prostacyclin of human umbilical vein endothelial cells was measured by the ELISA technique under basal conditions and after stimulation with calcium ionophore A 23187 10 μmol or histamine 0.1 μmol in the absence and presence of 1 and 2 minimal alveolar concentrations (MAC) of sevoflurane or isoflurane.

Results: The basal production of prostacyclin was unaffected by the volatile anaesthetics. Stimulation of endothelial cells increased prostacyclin formation 3–5-fold. Sevoflurane at 2 MAC, but not at 1 MAC, could reduce stimulated prostacyclin production by about half (P < 0.05). Isoflurane had no inhibitory effect. Inhibition of cyclo-oxygenase function by acetylsalicylic acid abolished the induced burst of prostacyclin formation completely.

Conclusions: Sevoflurane, but not isoflurane, can reduce stimulated endothelial prostacyclin production in a concentration-dependent manner. Because at least 2 MAC of sevoflurane were required, this effect should be of minor importance under clinical conditions of balanced anaesthesia.

Summary

Background and objective: Phosphodiesterase-III inhibitors and dobutamine effectively improve cardiac function in patients with cardiac failure, but they are limited by possible hypotensive effects. We tested the hypothesis that dopamine contributes to stabilizing milrinone-induced haemodynamic changes.

Methods: Nine patients undergoing major surgery were anaesthetized using nitrous oxide and oxygen supplemented with isoflurane 1–2%. After baseline haemodynamics were recorded, milrinone (25 or 50 μg kg−1) was administered over 10 min, followed by a continuous infusion (0.5 μg kg−1 min−1). The second set of haemodynamic values was measured 50 min after beginning the continuous infusion of milrinone. Dopamine (4 μg kg−1 min−1) was then administered with milrinone.

Results: Milrinone significantly increased the heart rate from 81 ± 8 to 102 ± 16 beats min−1, but it decreased the mean arterial pressure from 83 ± 10 to 66 ± 10 mmHg and systemic vascular resistance (P < 0.05 for each). The pulmonary capillary wedge pressure, cardiac index and pulmonary vascular resistance did not change significantly. The addition of dopamine to the milrinone infusion significantly decreased the heart rate (94 ± 12 beats min−1) and increased the mean arterial pressure (82 ± 11 mmHg). Dopamine and milrinone, but not milrinone alone, significantly increased the cardiac index and the rate–pressure product.

Conclusions: The combination regimen of milrinone and dopamine improved cardiac function, and changes in heart rate and mean arterial pressure induced by milrinone were attenuated by dopamine. The results suggest that a combination regimen of milrinone and dopamine rather than milrinone alone should be used to maintain arterial pressure.

Summary

Background and objective: Stable drug concentrations must be administered to provide adequate patient-controlled epidural analgesia. This study investigated the stability of sufentanil after the epidural delivery system had been flushed with solutions containing the drug.

Methods: Sufentanil citrate, 5 μg mL−1 was injected through an epidural catheter system into a glass container. The concentrations of the drug leaving the system, in 1 mL aliquots (1–5 mL) were measured using high-performance liquid chromatography. In the same manner, sufentanil samples were analysed after flushing the filter, as well as after priming the filter and catheter.

Results: ANOVA for repeated measurements demonstrated that sufentanil concentrations remained constant as long as the catheter had been adequately flushed. However, the concentration of sufentanil in the solution exiting the filter was reduced significantly. Hardly any sufentanil could be detected (0.09 ± 0.01 μg mL−1, P < 0.001) in the first 1 mL aliquot (probe) leaving the filter. Altogether, 3 mL sufentanil solution was needed to pass through the filter before the baseline values were restored (P < 0.05). The greatest decrease occurred when the whole epidural delivery apparatus (catheter and filter) was primed; to regain baseline values, as much as 4 mL solution was needed to flush the system.

Conclusions: Sufentanil citrate is adsorbed by the materials used to manufacture systems (catheters, filters) used in epidural anaesthesia. Hence, the epidural catheter system should be primed with sufentanil before connecting it to the patient so as to deliver reliable concentrations.

Summary

Background and objective: μ-agonistic opioids cause concentration-dependent hypoventilation and increased irregularity of breathing. The aim was to quantify opioid-induced irregularity of breathing and to investigate its time-course during and after an opioid infusion, and its ability to predict the severity of respiratory depression.

Methods: Twenty-three patients breathing spontaneously via a continuous positive airway pressure (CPAP) mask received an intravenous (i.v.) infusion of alfentanil (2.3 μg kg−1 min−1, 14 patients) or pirinitramide (piritramide) (17.9 μg kg−1 min−1, nine patients) until either a cumulative dose of 70 μg kg−1 for alfentanil or 500 μg kg−1 for pirinitramide had been achieved or the infusion had to be stopped for safety reasons. Tidal volumes (VT) and minute ventilation were measured with an anaesthesia workstation. For every 20 breaths, the quartile coefficient was calculated (Qeff20VT).

Results: Both the decrease of minute volume and the increase of Qeff20VT during and after opioid infusion were highly significant (P < 0.001, ANOVA). Patients in which the alfentanil infusion had to be terminated prematurely had lower minute volumes (P = 0.002, t-test) and higher Qeff20VT (P = 0.034, t-test) than those who received the complete dose. Changes in the regularity of breathing measured as Qeff20VT parallel those of minute ventilation during and after opioid infusion.

Conclusions: Opioids cause a more complicated disturbance of the control of respiration than a mere resetting to higher PCO2. Furthermore, Qeff20VT appears to predict the severity of opioid-induced respiratory depression.

Summary

Background and objective: The study investigated the impact of induced arterial hypotension for the facilitation of endovascular stent-graft placement in patients with thoracic aortic aneurysm on cerebral blood flow velocity and neurological/neurocognitive outcome.

Methods: In 27 ASA III patients, cerebral blood flow velocity was recorded during induced arterial hypotension for endovascular stent-graft placement using transcranial Doppler sonography and the Folstein Mini Mental State Examination and the National Institute of Health Stroke Scale were performed before and after the intervention.

Results: Mean arterial pressure was decreased <50 mmHg, and in 22 patients it was <40 mmHg. Diastolic cerebral blood flow velocity decreased by 59%. Postoperatively, six of 21 patients exhibited changes in the Folstein Mini Mental State Examination and four of these six patients in the National Institute of Health Stroke Scale as indices of new-found neurocognitive dysfunction, but there were no signs of stroke. Loss of the diastolic blood flow profile was detected in two of six patients with new-found neurocognitive dysfunctions and in 18 of 21 patients with no new-found neurocognitive dysfunction. Changes in the Folstein Mini Mental State Examination on postoperative day 1 were correlated to the pre-procedural Folstein Mini Mental State Examination, but not to the time spent with a mean arterial pressure <50 mmHg, <40 mmHg or with a loss of diastolic blood flow profile.

Conclusions: Transcranial Doppler sonography visualizes the individual effect of induced hypotension and the period of intracranial circulatory arrest during aortic stent-graft placement. However, transient new-found neurocognitive dysfunctions occur independently of the transcranial Doppler data, and are in close correlation to the neurocognitive state before the procedure. The results suggest that induced arterial hypotension is not the major factor for postoperative new-found neurocognitive dysfunction.

Summary

Background and objective: This study examined the quality of analgesia together with the side-effects produced by tramadol compared with morphine using intravenous patient-controlled analgesia during the first 24 h after thoracotomy.

Methods: Forty-four patients scheduled for thoracotomy were included in the study. Morphine 0.3 mg kg−1 was given interpleurally 20 min before a standard general anaesthetic. In the postanaesthetic care unit, the patients were randomly allocated to one of two groups to self-administer tramadol or morphine using a patient-controlled analgesia device throughout a 24 h period. The patient-controlled analgesia device was programmed to deliver tramadol 20 mg as an intravenous bolus or morphine 2 mg with a lockout time of 10 min.

Results: Mean cumulative morphine and tramadol consumption were 48.13 ± 30.23 and 493.5 ± 191.5 mg, respectively. There was no difference in the quality of analgesia between groups. Five (26.3%) patients in the tramadol group and seven (33%) in the morphine group had nausea, and three of the latter patients vomited. The incidence rate of vomiting with tramadol was 5.2%. All vital signs were within safe ranges. Sedation was less in the tramadol group, but not statistically significant.

Conclusions: In this clinical setting, which includes interpleural morphine pre-emptively, postoperative analgesia provided by tramadol was similar to that of morphine at rest and during deep inspiration. Side-effects were slight and comparable between the patients receiving morphine and tramadol.

Summary

Background and objective: Because gastric mucosal PCO2 must be referenced to arterial values via a gastric-to-arterial PCO2 gap (Pg–aCO2), the gastric-to-end-tidal PCO2 difference (Pg–etCO2) may be proposed as a surrogate method to monitor Pg–aCO2. However, the influence of arterial-to-end-tidal PCO2 (Pa–etCO2) on its value remains unknown. Pa–etCO2 may be enhanced by a low cardiac output and subsequent reduced perfusion of the lungs. This study was designed to compare such gaps observed during abdominal surgery in patients with or without preoperative cardiac dysfunction.

Methods: Haemodynamic, metabolic and tonometric variables were measured in seven patients with Crohn's disease and in five patients with chronic heart failure scheduled for abdominal surgery. Data were collected before skin incision (T0); at extractor placement (T1), 30 (T2) and 60 (T3) min later; at organ extraction (T4), 30 (T5) and 60 (T6) min later, and at the end of surgery (T7).

Results: Gradients appeared larger in the cardiac group. The difference was significant for Pg–etCO2 during the whole study period, while it was only reached at T1–T2 for Pa–etCO2 and at T5–T6 for Pg–aCO2. Gaps did not change significantly over the peroperative time points in either group. No major haemodynamic variations were registered in either group.

Conclusions: In patients with preoperative chronic heart failure, Pg–etCO2 remained constant throughout a major general surgical procedure and was only moderately influenced by the Pa–etCO2 gap. In these patients, Pg–etCO2 may be used as a reliable index of gastrointestinal perfusion after control of PaCO2.

Summary

Background and objective: Although many antiemetic drugs are available for intravenous use in the hospital setting, few are available after patient discharge. Consequently, nausea and vomiting are frequent complaints from patients at home after ambulatory surgery. We tested the hypothesis that the new 8 mg ondansetron disintegrating tablets will decrease the rate of nausea and vomiting at home after laparoscopic surgery.

Methods: Ninety-six patients were studied in a randomized double-blind study. Starting the first evening after operation and continuing every 12 h for 3 days, patients received either placebo or ondansetron 8 mg disintegrating tablets orally. The patients returned a questionnaire about postoperative nausea and vomiting, other side-effects, e.g. dizziness, headache, nightmare, anxiety and pain, as well as their overall satisfaction at 24 and 72 h after completion of surgery.

Results: The rates of nausea and vomiting were similar in the two groups, both during the first 24 h (28 versus 48%, placebo and ondansetron, respectively (ns) and during the 24–72 h (21 versus 35% (ns)). The incidence rate of vomiting was 8% (placebo) versus 12% (ondansetron) during the first 24 h (ns) and 9 versus 13% respectively in the 24–72 h (ns). No difference between groups was observed in overall satisfaction, incidence of postoperative pain or other side-effects.

Conclusions: The use of ondansetron disintegrating tablets of 8 mg twice a day for 3 days did not reduce the incidence of nausea and vomiting in patients undergoing outpatient laparoscopic surgery.

Summary

Background and objective: The incidence of pain associated with the injection of propofol still remains a problem. This study sought to examine the analgesic effects of inhaled nitrous oxide in oxygen on the prevention of propofol injection pain.

Methods: Nitrous oxide in oxygen was compared with a lidocaine (20 mg)–propofol mixture and with propofol alone (control) in a prospective, randomized, observer-blinded study. ASA I and II patients (n = 135) scheduled for elective surgical procedures were studied. A standard propofol injection technique and scoring system to measure the pain on injection was used.

Results: Demographic variables were similar between the study groups. Without analgesia (control) 26 of 45 patients (58%) reported pain on injection compared with 11 of 45 patients (24%) in both the nitrous oxide (95% CI: 14–52%, P = 0.001) and lidocaine groups (95% CI: 14–52%, P = 0.001).

Conclusions: The inhalation of a nitrous oxide/oxygen mixture significantly reduces the incidence of pain during propofol injection. This therapeutic stratagem was as effective as a lidocaine–propofol mixture.