Endocrine stress reaction, hemodynamics and recovery in total intravenous and inhalation anesthesia. Propofol versus isoflurane

This prospective, randomised study compared total intravenous anaesthesia (TIVA) and inhalation anaesthesia with respect to endocrine stress response, haemodynamic reactions, and recovery. METHODS. The investigation included two groups of 20 ASA I-II patients 18-60 years of age scheduled for orthopaedic surgery. For premedication of both groups, 0.1 mg/kg midazolam was injected IM. Patients in the propofol group received TIVA (CPPV, PEEP 5 mbar, air with oxygen FiO2 33%) with propofol (2 mg/kg for induction followed by an infusion of 12-6 mg/kg.h) and fentanyl (0.1 mg before intubation, total dose 0.005 mg/kg before surgery, repetition doses 0.1 mg). For induction of patients in the isoflurane-group, 5 mg/kg thiopentone and 0.1 mg fentanyl was administered. Inhalation anaesthesia was maintained with 1.2-2.4 vol.% isoflurane in nitrous oxide and oxygen at a ratio of 2:1 (CPPV, PEEP 5 mbar). For intubation of both groups, 2 mg vecuronium and 1.5 mg/kg suxamethonium were injected, followed by a total dose of 0.1 mg/kg vecuronium. Blood samples were taken through a central venous line at eight time points from before induction until 60 min after extubation for analysis of adrenaline, noradrenaline (by HPLC/ECD), antidiuretic hormone (ADH), adrenocorticotropic hormone (ACTH), and cortisol (by RIA). In addition, systolic arterial pressure (SAP) heart rate (HR), arterial oxygen saturation (SpO2), and recovery from anaesthesia were observed. RESULTS. Group mean values are reported; biometric data from both collectives were comparable (Table 1). Plasma levels of adrenaline (52 vs. 79 pg/ml), noradrenaline 146 vs. 217 pg/ml), and cortisol (82 vs. 165 ng/ml) were significantly lower in the propofol group (Table 2, Figs. 1 and 3). Plasma levels of ADH (4.8 vs. 6.1 pg/ml) and ACTH (20 vs. 28 pg/ml) did not differ between the groups (Table 2, Figs 2 and 3). SAP (128 vs. 131 mmHg) was comparable in both groups, HR (68/min vs. 83/min) was significantly lower in the propofol group, and SpO2 (97.1 vs 97.4%) showed no significant difference (Table 3). Recovery from anaesthesia was slightly faster in the propofol group (following of simple orders 1.9 vs. 2.4 min, orientation with respect to person 2.4 vs. 3.4 min, orientation with respect to time and space 2.8 vs. 3.7 min), but differences failed to reach statistical significance. CONCLUSIONS. When compared with isoflurane inhalation anaesthesia, moderation of the endocrine stress response was significantly improved during and after TIVA with propofol and fentanyl. Slightly shorter recovery times did not lead to an increased stress response. With respect to intra- and postoperative stress reduction, significant attenuation of sympatho-adrenergic reaction comparable SAP and reduced HR, sympatholytic and hypodynamic anaesthesia with propofol and fentanyl seems to be advantageous for patients with cardiovascular and metabolic disorders. For this aim, careful induction and application of individual doses is essential.     

Propofol, but not thiopentone or etomidate, enhances isoflurane-induced coronary vasodilatation in dogs

PURPOSE: To test the hypothesis that thiopentone, propofol, and etomidate alter the coronary vascular effects of abruptly administered isoflurane. METHODS: Dogs (n = 6) received inspired isoflurane 5% in the presence of thiopentone (20 mg.kg-1 induction dose and 20 mg.kg-1.hr-1 infusion), propofol (5 mg.kg-1 induction dose and 40 mg.kg-1.hr-1 infusion), etomidate (2 mg.kg-1 induction dose and 5 mg.kg-1.hr-1 infusion), or isoflurane (1.0 MAC) anaesthesia in a random fashion. Haemodynamics were assessed in the conscious state, during baseline anaesthesia, and at 30 sec intervals for five minutes after beginning isoflurane 5%. RESULTS: Rapidly administered isoflurane caused greater (P < 0.05) reductions in coronary vascular resistance in thiopentone- or propofol--than in isoflurane-anaesthetized dogs. Isoflurane produced greater (P < 0.05) increases in the ratio of coronary blood flow velocity to pressure-work index (an index of myocardial oxygen consumption; +109 +/- 19% during isoflurane alone vs +182 +/- 27% change from baseline during propofol and isoflurane) consistent with relatively greater direct coronary vasodilatation during baseline propofol than during baseline isoflurane anaesthesia. Isoflurane caused larger increases in coronary blood flow velocity in dogs anaesthetized with etomidate concomitant with higher coronary perfusion pressure and pressure-work index than in those anaesthetized with isoflurane alone. CONCLUSIONS: The results suggest that thiopentone, propofol, and etomidate each uniquely modify the coronary vascular responses to abrupt administration of high inspired concentrations of isoflurane in chronically instrumented dogs.     

The independent metabolic effects of halothane and isoflurane anaesthesia

Twelve healthy, unpremedicated women scheduled for total abdominal hysterectomy were given either isoflurane (n = 6) or halothane (n = 6) anaesthesia. They all received general anaesthesia for a period of 3 h, with surgery being carried out only in the last hour. The anaesthesia consisted of thiopentone, pancuronium and a mixture of oxygen-enriched air (FiO2 = 34%) supplemented with 1 MAC of either isoflurane or halothane. The patients were maintained normothermic, and with an arterial SaO2 above 95% throughout the period of the study. The following measurements were made before, during and after anaesthesia (with and without surgery): oxygen consumption (VO2), carbon dioxide production (VCO2); circulating concentrations of various hormones (insulin, growth hormone and cortisol); various metabolites; selected amino acids and albumin; forearm arterio-venous concentration difference of glucose, lactate, free fatty-acids and selected amino acids (four patients in each group). Whole body VO2 decreased significantly by over 20% during anaesthesia (with or without surgery), P < 0.05). Although the circulating concentration of most amino acids showed little or no change during anaesthesia alone, there was a tendency for the flux of most metabolites to decrease, and this persisted during surgery (P < 0.05). During anaesthesia alone there was a twofold reduction in the plasma cortisol concentration (P < 0.05), and a decrease in albumin concentration (P < 0.01). With the onset of surgery, plasma cortisol concentration increased rapidly (in association with several other hormones and metabolites) but hypoalbuminemia persisted.     

Laparoscopic cholecystectomy: evaluation of intraoperative complications with respect to 2 different kinds of anesthesia

Two anaesthetic managements for elective laparoscopic cholecystectomy were compared in 64 patients in order to investigate some perioperative complications: 1) bowel distension during surgery. 2) recovery from anaesthesia. 3) post-surgery incidence of emesis and pain. In addition, the quality of postoperative peristalsis as well as the time of dimissal were recorded. Group I (n = 30) was treated with NLA in N2O-O2 and Group II (n = 34) received propofol plus fentanyl in air-O2. Bowel distension, evaluated by surgeon at 15 min intervals throughout the operation was similar in both the groups as well as postoperative peristalsis recuperation. During the first 12 hours after laparoscopy no differences were found at any times of observation in the incidence or severity of emesis and pain between the two different anaesthesia patients. In subjects which were given propofol the psychomotor recovery was more rapid than after NLA, particularly during the first 6 hours after surgery. The patients were discharged between 36-48 hours following the operation independently from anaesthetic management. It is concluded that both the anaesthetic techniques provide similar intra/postoperative conditions, except the early recovery that is more rapid for the propofol patients. The overall frequency of emesis and pain was rather high in both the groups, suggesting a routine medication with analgesics and antiemetics.     

Propofol, isoflurane and neuroleptanesthesia. Ophthalmic surgery in geriatric patients

Ophthalmic surgeons require anaesthesia to ensure that the patient is completely relaxed for microsurgical operations and that the intraocular pressure is reduced. These conditions must be maintained throughout the operation. In addition to these requirements, the anaesthetist mostly deals with elderly patients with multiple diseases. Although earlier studies have shown which general or local anaesthesia is preferred for which patients and operations, studies on which general anaesthesia technique is ideal to fulfil these requirements are still lacking. The aim of this study was to show which technique causes the least stress for a geriatric patient undergoing an ophthalmic operation, propofol/fentanyl anaesthesia, isoflurane anaesthesia or neuroleptanaesthesia. PATIENTS AND METHODS. Sixty patients aged 60 years and above were included in this study. After being randomly allocated to either propofol/fentanyl (continuous propofol infusion), isoflurane or neuroleptanaesthesia, they underwent ophthalmic surgery. Intraoperative complications (cardiocirculatory changes) and surgical conditions were recorded. After the operation, patient vigilance and post-operative pain reactions (nominal pain score) were assessed over 8 h by means of simple reaction tests and the Juhl index. Within the first 2 h after surgery, cardiocirculatory changes were also documented and arterial blood gases measured. RESULTS. The treatment groups did not differ with respect to general biometric data, preoperative risk or operations carried out. Intraoperative cardiocirculatory changes and the resulting therapy (positive inotropic drugs, volume replacement fluids) were similar in all groups. The surgical conditions were equally good in all groups. Apart from a lower rate pressure product in the first 60 min after propofol/fentanyl anaesthesia, there were no postoperative differences in cardiocirculatory parameters or blood gases. After isoflurane anaesthesia the time until the patients were able to give their names and perform the finger-nose test properly was longer than that after neurolept-anaesthesia or propofol anaesthesia. After propofol anaesthesia the patients could perform simple tests earlier and were more alert over the whole monitoring period than after isoflurane or neuroleptanaesthesia. On the other hand, the patients in the neuroleptanaesthesia group had fewer pain complaints than those in the two groups compared. DISCUSSION. None of the anaesthesia techniques used in this study showed an intraoperative advantage. This is not surprising since all anaesthetics, with the exception of ketamine, reduce intraocular pressure. The prerequisite, however, is careful monitoring of anaesthesia in elderly patients in order to avoid cardiocirculatory changes, mild hyperventilation and coughing and pressing at the end of the operation. Until this point in time no change in the depth of anaesthesia is allowed. Therefore, it seems on the whole that there are benefits from propofol-fentanyl anaesthesia because of the fact that in comparison with the rather techniques, elderly patients become alert again faster. However, sufficient postoperative pain therapy is necessary to free the patients of pain to the same degree as with neuroleptanaesthesia. In most cases peripherally acting analgesic substances with no interference with vigilance are sufficient.     

Dreams, images and emotions associated with propofol anaesthesia

One hundred and twelve patients scheduled for day case varicose vein surgery were randomly allocated to one of three groups: total intravenous anaesthesia with propofol, propofol induction followed by inhalational anaesthesia with nitrous oxide and isoflurane or thiopentone induction followed by inhalational anaesthesia with nitrous oxide and isoflurane. Assessments were made in the recovery room of the incidence of dreaming, the content of the dreams and the emotional status of the patients. The groups differed significantly in reporting that they had been dreaming: patients who underwent total intravenous anaesthesia reported the most dreaming and patients who received thiopentone the least. However, despite the large number of case reports of sexual imagery following propofol anaesthesia and despite the two groups who had received propofol experiencing significantly greater happiness upon recovery than the thiopentone group, there were no appreciable differences in the sexual content of the dreams. Each group had only a small number of dreams even remotely related to sex.     

Influence of anesthetic technique in postoperative analgesia in thoracic surgery

OBJECTIVE: To compare the intensity of postoperative pain after thoracotomy with 2 anesthetic techniques: 1) thoracic epidural block with bupivacaine administered before surgery (combined anesthesia with isoflurane) and 2) conventional balanced anesthesia with isoflurane and endovenous fentanyl. PATIENTS AND METHODS: Thirty patients scheduled for thoracotomy by lateral incision (T5-T6) were randomly divided into 2 groups of 15. Group A received 8 ml of 0.5% bupivacaine with adrenalin 1:200.000 30 min before start of surgery while group B received 8 ml saline solution through an epidural catheter inserted to T4-T8. Combined anesthesia (4 ml 0.5% bupivacaine through an epidural catheter 150 min after the first dose and isoflurane in 100% oxygen) was used in group A. Group B received balanced anesthesia with endovenous fentanyl 2.5 micrograms/kg and isoflurane in 100% oxygen. The difference in pain intensity during postoperative recovery was assessed by way of the following variables: number of boluses administered by epidural patient-controlled analgesia (bupivacaine 0.0625% and fentanyl 6 micrograms/ml); score on a visual analog scale of 10 at baseline and at 1, 3, 7, 11, 19 and 43 hours after surgery; and need for additional analgesia (diclofenac) during the 43 hours of study. Arterial gases were measured during the preoperative period and at 1, 3, 7, 19 and 43 hours after surgery. RESULTS: No significant differences in pain intensity measured on the visual analog scale, by the number of boluses per patients or by need for additional analgesia were found between the 2 groups. The total number of boluses administered and additional analgesic requirements were greater in the group receiving bupivacaine, although the difference was not significant (p = 0.095 and p = 0.056, respectively). Nor were there significant differences in pH and PaCO2 levels for the 2 groups. CONCLUSIONS: Analgesic efficacy after thoracotomy was similar for our 2 groups receiving either combined anesthesia (epidural bupivacaine at 0.5% and isoflurane) or balanced anesthesia with isoflurane and endovenous fentanyl.     

Effect of propofol as an agent for anesthetic induction on pituitary-adrenocortical function during anesthesia and surgery

Effect of propofol as an agent for anesthetic induction on plasma levels of cortisol, beta-endorphin-like immunoreactivity (beta-ELI), growth hormone (GH) and prolactin were evaluated in 20 non-abdominal surgical patients ranged in ages from 19 to 64 years. Anesthesia was induced with either intravenous propofol 2-2.5 mg in ten patients or intravenous thiopental 4-5 mg in the remaining 10 patients as the control group, and succinylcholine was administered intravenously to facilitate tracheal intubation. Enflurane-nitrous oxide-oxygen was then given to maintain anesthesia in all the patients of both groups. Plasma cortisol levels decreased slightly with anesthesia in the propofol group, but they increased slightly after anesthetic induction in the control group. Therefore they were significantly lower in the propofol group than those in the control group. They tended to increase gradually during surgery and reached the peak value after the emergence from anesthesia in both groups. Plasma beta-ELI levels were unchanged with anesthesia alone in the patients of both groups. They tended to increase gradually during surgery and reached the peak value after the emergence from anesthesia in both groups. Plasma GH levels were not affected with anesthesia, but they increased slightly during surgery in both groups. Plasma prolactin levels increased significantly during anesthesia and surgery in both groups, and they decreased after the emergence from anesthesia but were still significantly higher than the preanesthetic values in both groups. The authors' findings suggest that effects of propofol as an agent for anesthetic induction on pituitary-adrenocortical function during anesthesia and surgery are comparable to those of thiopental, and that propofol does not exert inhibitory effect on pituitary-adrenocortical function during anesthesia and surgery.     

Comparison of the haemodynamic actions of desflurane/N2O and isoflurane/N2O anaesthesia in vascular surgical patients

BACKGROUND: The purpose of this study was to compare heart rate and arterial blood pressure response to desflurane/N2O vs isoflurane/N2O anaesthesia in a randomized clinical trial performed in patients before vascular surgery. METHODS: To evaluate associated changes in the autonomic nervous system with maintenance of anaesthesia, we used power spectral analysis (PSA) of heart rate and blood pressure and measured plasma catecholamine concentrations. Twenty-five patients whose trachea had been intubated after propofol induction were given either desflurane or isoflurane at 1 and 1.5 MAC in N2O (60%) in a random manner. RESULTS: At an anaesthetic depth of up to 1.5 MAC, arterial blood pressure, indices of sympathetic activity derived from PSA, decreased with both anaesthetics, while heart rate and plasma catecholamine concentrations did not significantly change. Plasma renin activity significantly increased at 1.5 MAC anaesthesia in both groups. CONCLUSIONS: We conclude that sympathetic hyperactivity previously reported during desflurane anaesthesia in healthy volunteers is not frequent in clinical practice in elderly vascular surgical patients under desflurane/N2O anaesthesia, since it occurs at an anaesthetic depth which cannot be reached in these patients because of the lowering arterial blood pressure effects of desflurane, which are similar to those of isoflurane.     

Night blindness secondary to vitamin A deficiency in a patient with bile duct strictures after liver transplantation

We have studied the incidence of gastro-oesophageal reflux associated with the laryngeal mask airway (LMA) in 82 paralysed patients undergoing ventilation for elective orthopaedic surgery. Anaesthesia was managed by skilled LMA users. A pH-sensitive probe was passed nasally into the oesophagus before induction and recordings made during five phases of anaesthesia. Anaesthesia was induced with propofol and fentanyl and maintained with 0.5-1.5% isoflurane and nitrous oxide in oxygen. Neuromuscular block was produced with vecuronium and the train-of-four count maintained at < or = 1. Towards the end of surgery, neuromuscular function was allowed to recover spontaneously. All LMAs were inserted at the first attempt and ventilation was successful in all patients. There were no adverse airway events. Mean oesophageal pH values during each phase of anaesthesia were: before insertion 5.88 (SD 0.77), placement 5.85 (0.74), maintenance 5.89 (0.73), emergence 5.71 (0.78) and removal 5.82 (0.75). There were no reflux events (pH < 4.0) during any phase of anaesthesia. We conclude that the incidence of gastro-oesophageal reflux is low in paralysed patients undergoing ventilation for elective orthopaedic surgery when antagonism of neuromuscular block is avoided. The validity of these findings for unskilled LMA users is unknown.     

Hepatocellular integrity during and after isoflurane and halothane anaesthesia in surgical patients

Subclinical disturbance in hepatocellular integrity, indicated by glutathione transferase Alpha (GSTA), has been associated with halothane, sevoflurane and propofol, but not with isoflurane anaesthesia. We anaesthetized 82 patients with isoflurane or halothane at 1 MAC for superficial surgery. GSTA concentration were measured with a sensitive time-resolved immunofluorometric assay in serum samples. GSTA concentrations increased from a baseline value of geometric mean 1.8 micrograms litre-1 (95% confidence intervals 1.4-2.2 micrograms litre-1) to a peak of 4.3 (3.3-5.7) micrograms litre-1 in the isoflurane group and from 2.1 (1.6-2.9) micrograms litre-1 to 6.2 (4.1-9.5) micrograms litre-1 in the halothane group. The change in GSTA was significant within groups but the difference between groups was not significant. Two patients exhibited an unexpectedly large increase in GSTA (peaks 370 and 620 micrograms litre-1) and a mild increase in alanine aminotransferase after halothane anaesthesia. We conclude that hepatocellular integrity was mildly disturbed after isoflurane and halothane anaesthesia but there was no difference between anaesthetics. Halothane anaesthesia may be associated with more advanced hepatocellular disturbance in some cases.     

Identification of entero-aggregative Escherichia coli based on surface properties

OBJECTIVES: Afterdrop in core temperatures after discontinuation of cardiopulmonary bypass (CPB) is reported to be a sign of inadequate total body rewarming on CPB. The purpose of this study was to compare the effects of three different drug regimens on hemodynamic stability and the uniformity of rewarming during the rewarming period of CPB. DESIGN: This prospective randomized study was performed in the Anesthesiology Department of the University of Istanbul. PARTICIPANTS: Sixty-six patients undergoing uncomplicated valve replacement and aortocoronary bypass grafting surgery were studied. INTERVENTIONS: Anesthesia was maintained with isoflurane and fentanyl infusion during the prebypass and the postbypass periods. Patients were allocated into three groups by the initiation of CPB. Group 1 (n = 22): fentanyl infusion + diazepam + sodium nitroprusside (SNP) in the rewarming period), group 2 (n = 22): fentanyl infusion + isoflurane, group 3, control (n = 22): fentanyl infusion + diazepam. Rectal, esophageal, and forearm temperatures were monitored throughout the study. MEASUREMENTS AND MAIN RESULTS: None of the durational and temperature data showed significant differences between groups 1 and 2. In the control group, afterdrop in esophageal temperature was significantly higher than groups 1 and 2 (group 1: -1.4 +/- 0.9 degrees C, group 2: -1.44 +/- 0.8 degrees C, group 3: -2.1 +/- 0.65 degrees C). In group 1, the number of patients whose mean arterial pressure (MAP) decreased below 45 mmHg was significantly higher than group 2 (p = 0.002). Mean SNP infusion rate and mean isoflurane concentration during the rewarming period were calculated as 1.55 +/- 0.8 micrograms/kg/min and 0.775 +/- 0.27%, respectively. CONCLUSIONS: Isoflurane produced more stable hemodynamic conditions than SNP during the rewarming period, improved the uniformity of rewarming, and permitted earlier extubation in the intensive care unit (ICU). It is concluded that isoflurane alone is capable of fulfilling the anesthesia needs during hypothermia and the rewarming period of CPB.     

Potency and time course of action of rocuronium during desflurane and isoflurane anaesthesia

We have studied the potency and onset and duration of action of rocuronium in patients anaesthetized with 1 MAC of desflurane or isoflurane (in 66% nitrous oxide). Potency was estimated using the single bolus dose technique. Neuromuscular block was measured by stimulation of the ulnar nerve and recording the force of contraction of the adductor pollicis muscle. The ED50 and ED95 of rocuronium were estimated as 138 (95% confidence limits 117-162) micrograms kg-1 and 281 (241-328) micrograms kg-1, and 126 (105-151) micrograms kg-1 and 283 (236-339) micrograms kg-1 during desflurane and isoflurane anaesthesia, respectively. The mean times to onset of maximum block after rocuronium 0.6 mg kg-1 were 1.0 (SD 0.10) min and 1.1 (0.15) min, respectively, during anaesthesia with desflurane and isoflurane. The respective times to recovery of T1 (the first response in the train-of-four (TOF) stimulation) to 25% and 90% were 36 (8.3) min and 54 (15.4) min during desflurane anaesthesia and 31 (8.2) min and 45 (12.7) min during isoflurane anaesthesia. The times to recovery of the TOF ratio to 0.7 were 66 (13.4) min and 52 (16.3) min and the 25-75% recovery indices 14 (5.3) min and 10 (3.2) min, respectively, in the desflurane and isoflurane groups. There were no differences in the estimated potency or onset of action of rocuronium during desflurane and isoflurane anaesthesia. However, duration of action tended to be longer curing desflurane anaesthesia although only the differences in times to TOF ratio of 0.7 and the recovery indices were close to being significantly different (P = 0.0503 and 0.0560).     

Comparative study of propofol emulsions for anesthesia in varicose vein operations

PURPOSE: It is commonly known that propofol-based anaesthesia is easily controlled and well tolerated. These advantages of propofol are partly offset by the comparably high costs of the anaesthetic. The present prospective randomised double-blind cross-over study compared two propofol emulsions with regard to their efficacy and drug safety. METHODS: 30 patients were included in this study. All patients underwent two propofol-based anaesthesias for leg vein surgery on both legs within 2-4 days. The patients were randomised in two treatment groups where Group A (n = 15) received the investigational drug for the 2nd anaesthesia and the control drug for the 1st anaesthesia. The order of drug application was reversed for Group B (n = 15). The propofol induction doses, the maintenance doses, and the side effect profiles were evaluated for the purpose of comparing the two propofol emulsions. RESULTS: The study showed no differences in the efficacy of the two propofol emulsions. Furthermore, the side effect profiles were almost identical and did not reveal any unknown side effects of propofol. CONCLUSIONS: The results clearly demonstrate that both propofol emulsions are comparably well suited for vascular surgery anaesthesia. This study demonstrates a methodological clinical approach to compare the same medication supplied by different manufacturers.     

Intraoperative modulation of alveolar macrophage function during isoflurane and propofol anesthesia

BACKGROUND: Alveolar macrophages are a critical part of the defense against pulmonary infection. Thus the authors determined time-dependent changes in alveolar macrophage functions in patients having surgery who were anesthetized with isoflurane or propofol. METHODS: Patients anesthetized with propofol (n = 30) or isoflurane (n = 30) during orthopedic surgery were studied. Alveolar macrophages were harvested by bronchoalveolar lavage immediately, and 2, 4, and 6 h after induction anesthesia and at the end of surgery. The fraction of aggregated and nonviable macrophages was determined. Then phagocytosis was measured by ingestion of opsonized and unopsonized particles. Finally, microbicidal activity was determined as the ability of the macrophages to kill Listeria monocytogenes directly. RESULTS: Demographic and morphometric characteristics of the patients given propofol and isoflurane were similar, as were their levels of pulmonary function and hemodynamic responses. The fraction of alveolar macrophages ingesting opsonized and unopsonized particles, and the number of particles ingested, decreased significantly over time, with the decrease slightly but significantly greater during isoflurane anesthesia. Microbicidal function decreased progressively during anesthesia and surgery, with the decrease almost twice as great during isoflurane compared with propofol anesthesia. The fraction of aggregated macrophages and recovered neutrophils increased over time in the patients given each anesthetic. CONCLUSIONS: Pulmonary immunologic function changed progressively during anesthesia and surgery. The data from this study suggest that pulmonary defenses are modulated by the type of anesthesia and by the duration of anesthesia and surgery.     

Cardiopulmonary bypass-induced changes in plasma concentrations of propofol and in auditory evoked potentials

Unbound, rather than total, plasma concentrations may be related to the anaesthetic action of propofol. Therefore, we measured plasma concentrations of propofol and recorded Nb wave latencies of auditory evoked potentials (AEP) during continuous infusion of propofol in 15 patients undergoing coronary artery bypass grafting (CABG) surgery. After induction of anaesthesia with fentanyl, propofol was infused continuously at a rate of 10 mg kg-1 h-1 for 20 min, and then the rate was reduced to 3 mg kg-1 h-1. Administration of heparin before cardiopulmonary bypass (CPB) did not affect total or unbound propofol concentration. Initiation of CPB decreased mean total propofol concentration from 2.6 to 1.7 micrograms ml-1 (P < 0.01). Simultaneously, mean unbound propofol concentration remained at 0.06 micrograms ml-1 because of a slight increase in the mean free fraction of plasma propofol (from 2.3 to 3.5%; P > 0.05). During hypothermic CPB, mean total propofol concentration increased to concentrations measured before bypass (to 2.1 micrograms ml-1; P > 0.05 vs value before CPB) and the mean unbound propofol concentration was at its highest (0.07 microgram ml-1; P < 0.05 vs value before heparin). After CPB and administration of protamine, the mean total propofol concentration remained lowered (1.7 micrograms ml-1; P < 0.05 vs value before heparin) and the mean unbound propofol concentration returned to the level measured before heparin (P < 0.001 vs value during hypothermia). The latency of the Nb wave from recordings of AEP increased after induction of anaesthesia, reached its maximum during hypothermia and was prolonged during the subsequent phases of the study. The latency of the Nb wave did not correlate with total or unbound propofol concentration. We conclude that the changes in total and unbound concentrations of plasma propofol were not parallel in patients undergoing CABG. During CPB or at any other time during the CABG procedure, the unbound propofol concentration did not decrease and Nb wave latency was prolonged compared with baseline values measured after induction of anaesthesia before the start of CPB.     

Anesthesia with flunitrazepam/fentanyl and isoflurane/fentanyl. Unconscious perception and mid-latency auditory evoked potentials

There is a high incidence of intraoperative awareness during cardiac surgery. Mid-latency auditory evoked potentials (MLAEP) reflect the primary cortical processing of auditory stimuli. In the present study, we investigated MLAEP and explicit and implicit memory for information presented during cardiac anaesthesia. PATIENTS AND METHODS. Institutional approval and informed consent was obtained in 30 patients scheduled for elective cardiac surgery. Anaesthesia was induced in group I (n = 10) with flunitrazepam/fentanyl (0.01 mg/kg) and maintained with flunitrazepam/fentanyl (1.2 mg/h). The patients in group II (n = 10) received etomidate (0.25 mg/kg) and fentanyl (0.005 mg/kg) for induction and isoflurane (0.6-1.2 vol%)/fentanyl (1.2 mg/h) for maintenance of general anaesthesia. Group III (n = 10) served as a control and patients were anaesthetized as in I or II. After sternotomy an audiotape that included an implicit memory task was presented to the patients in groups I and II. The story of Robinson Crusoe was told, and it was suggested to the patients that they remember Robinson Crusoe when asked what they associated with the word Friday 3-5 days postoperatively. Auditory evoked potentials were recorded awake and during general anaesthesia before and after the audiotape presentation on vertex (positive) and mastoids on both sides (negative). Auditory clicks were presented binaurally at 70 dBnHL at a rate of 9.3 Hz. Using the electrodiagnostic system Pathfinder I (Nicolet), 1000 successive stimulus responses were averaged over a 100 ms poststimulus interval and analyzed off-line. Latencies of the peak V, Na, Pa were measured. V belongs to the brainstem-generated potentials, which demonstrates that auditory stimuli were correctly transduced. Na, Pa are generated in the primary auditory cortex of the temporal lobe and are the electrophysiological correlate of the primary cortical processing of the auditory stimuli. RESULTS. None of the patients had an explicit memory of intraoperative events. Five patients in group I, one patient in group II, and no patients in group III showed implicit memory of the intraoperative tape message. They remembered Robinson Crusoe spontaneously when they were asked their associations with Friday. In the awake state AEP peak latencies were in the normal range. During general anaesthesia in group I, the peaks Na, Pa did not increase in latency or decrease in amplitude before and after the audiotape presentation. The primary cortical complex Na/Pa could be identified as in the awake state. In contrast, in group II Na, Pa showed a marked increase in latency and a decrease in amplitude or were completely suppressed. CONCLUSIONS. During general anaesthesia auditory information can be processed and remembered postoperatively by an implicit memory function, when the electrophysiological conditions of primary cortical stimuli processing is preserved. Implicit memory can be observed more often when high-dose opioid analgesia is combined with receptor-binding agents like the benzodiazepines than under non-specific anaesthetics like isoflurane. Non-specific anaesthetics seem to provide a more effective suppression of auditory stimuli processing than receptor-specific agents.     

Nitrous oxide has different effects on the EEG and somatosensory evoked potentials during isoflurane anaesthesia in patients

BACKGROUND: Electroencephalogram (EEG) and somatosensory evoked potentials (SEPs) are altered by inhalation anaesthesia. Nitrous oxide is commonly used in combination with volatile anaesthetics. We have studied the effects of nitrous oxide on both EEG and SEPs simultaneously during isoflurane burst-suppression anaesthesia. METHODS: Twelve ASA I-II patients undergoing abdominal or orthopaedic surgery were anaesthetized with isoflurane by mask. After intubation and relaxation the isoflurane concentration was increased to a level at which an EEG burst-suppression pattern occurred (mean isoflurane end-tidal concentration 1.9 (SD 0.2) %. With a stable isoflurane concentration, the patients received isoflurane-air-oxygen and isoflurane-nitrous oxide-oxygen (FiO2 0.4) in a randomized cross-over manner. EEG and SEPs were simultaneously recorded before, and after wash-out or wash-in periods for nitrous oxide. The proportion of EEG suppressions as well as SEP amplitudes for cortical N20 were calculated. RESULTS: The proportion of EEG suppressions decreased from 53.5% to 34% (P < 0.05) when air was replaced by nitrous oxide. At the same time, the cortical N20 amplitude was reduced by 69% (P < 0.01). CONCLUSION: The results suggest that during isoflurane anaesthesia, nitrous oxide has a different effect on EEG and cortical SEP at the same time. The effects of nitrous oxide may be mediated by cortical and subcortical generators.     

In vitro effect of ketones and hyperglycemia on feline hemoglobin oxidation and D- and L-lactate production

Postoperative nausea and vomiting (PONV) are unpleasant, often underestimated side effects of anaesthesia and surgery, not devoid of medical complications. Prevention with antiemetics is only partially effective. Propofol has been shown recently to possess antiemetic properties in several situations. In this prospective, randomized, controlled trial, we have compared the antiemetic efficacy of subhypnotic doses of propofol, with Intralipid as placebo, after thyroidectomy. We studied 64 patients of both sexes, aged 22-71 yr, ASA I or II, undergoing thyroidectomy. After premedication with a benzodiazepine, balanced anaesthesia was produced with isoflurane and nitrous oxide in oxygen, and supplementary analgesia with fentanyl i.v. as required. Postoperative analgesia was provided with non-opioids, and piritramide 0.25 mg kg-1 i.m. on demand. Patients were allocated randomly and blindly to receive a 20-h infusion of either propofol or 10% Intralipid 0.1 ml kg-1 h-1. Intralipid, the excipient of propofol, was chosen as placebo as it is devoid of antiemetic effects. Sedation scores, respiratory and cardiovascular variables, and incidence of PONV were assessed every 4 h for 24 h. Pulse oximetry and ECG were monitored continuously. Both groups were comparable in characteristics, surgical and anaesthesia procedures, amount of opioids given during and after operation, and total amount of the study drug infused after operation. Occurrence of PONV was similar before the start (propofol 41%, Intralipid 50%) and after completion (propofol 0.64%, Intralipid 1.6%) of infusion and decreased with time in both groups during the infusion. However, symptoms were reduced to nil with propofol but persisted and were more severe with Intralipid during infusion (P < or = 0.01). The overall incidence of PONV during infusion was 10% (three of 32 patients) in the propofol group and 65% (21 of 32 patients) in the Intralipid group. Cardiovascular and respiratory variables, and SpO2 were unaltered, and sedation decreased similarly with time in both groups. We conclude that propofol, given at subhypnotic doses, effectively reduced the incidence of PONV without untoward sedative or cardiovascular effects.     

Thoracic epidural analgesia in aortocoronary bypass surgery. II: Effects on the endocrine metabolic response

Thoracic epidural analgesia (TEA) may offer haemodynamic benefits for patients with coronary heart disease going through major surgery. This may-in part-be secondary to an effect on the endocrine and metabolic response to surgery. We therefore investigated the effect of TEA on the endocrine metabolic response to aortocoronary bypass surgery (ACBS). Thirty male patients (age < 65 years, ejection fraction > 0.5) were randomized into 3 groups; the HF group receiving a high dose fentanyl (55 micrograms.kg-1) anaesthesia, the HF+TEA group with the same fentanyl dose+TEA with 10 ml bupivacain 5 mg.ml-1, followed by 4 ml every hour, and the LF+TEA group receiving fentanyl 15 micrograms.kg-1 + TEA. Adrenalin, noradrenalin, systemic vascular resistance (SVR), glucose, cortisol, lactate and free fatty acids were followed during the operation and for 20 h postoperatively. A significant increase in adrenalin, noradrenalin and SVR was found in the HF group whereas this increase was blocked in both epidural groups. An increase in glucose and cortisol was noticed in all groups, but the increase was delayed in the epidural groups. Our results suggest that a more effective blockade of the stress response during ACBS is obtained when TEA is added to general anaesthesia than with high dose fentanyl anaesthesia alone.