Propofol is a 'safe' anaesthetic agent in malignant hyperthermia susceptible patients.

In this study we investigated in vitro and in vivo effects of propofol in malignant hyperthermia susceptible (MHS) patients in order to assess the safety of propofol infusion as a non-triggering anaesthetic technique for diagnostic and therapeutic procedures. In vitro, human MHS muscle samples were exposed to propofol and changes in (a) baseline tension and (b) contracture tension on exposure to halothane and caffeine were measured. In vivo, (a) anaesthesia was induced in ten muscle biopsy positive MHS patients with propofol 2.5 mg/kg and (b) anaesthesia was produced in five muscle biopsy positive MHS patients with infusions of propofol up to 10 mg/kg/hr. In vitro, human MHS muscle did not develop contractures with propofol alone. Propofol had no significant effect on contracture development in response to halothane and caffeine. In vivo, no evidence of an MH response was detected following induction or maintenance of anaesthesia with propofol. Our results and literature review are in agreement that propofol is a 'safe' induction and maintenance agent in MHS patients. Propofol can be used for muscle biopsy anaesthesia because it does not alter the sensitivity of diagnostic muscle biopsy testing.     

Prilocaine reduces injection pain caused by propofol

Propofol, which is commonly used for outpatient anaesthesia, may evoke pain during infusion. Forty-eight patients (ASA I-II) undergoing elective uterine dilatation and curettage received randomly in a standardised fashion: A: Propofol mixed with prilocaine; B: Propofol and lidocaine; C: Propofol with prilocaine + lidocaine (equal amounts) or D: Propofol and saline. The final ratio of propofol: local anaesthetic/saline was 9: 1 in all mixtures. Pain on injection was significantly decreased in the three groups receiving propofol and local anaesthetic(s) compared to the one given propofol and saline. Propofol is required in greater amounts when mixed with lidocaine than when mixed with saline. A binding between the algesic part of the propofol molecule and the local anaesthetic agent may explain these findings. Another twenty-two comparable patients were given 30 mg of ketorolac or an equal volume of saline intramuscularly 45 60 minutes prior to propofol. Ketorolac given before propofol did not reduce pain on injection. This indicates that inhibition of the cyclooxygenase pathway of arachidonic acid metabolism does not play a major role in the reduction of this pain.     

Ketamine as analgesic for total intravenous anaesthesia with propofol

A prospective study of 18 patients who underwent noncardiac surgery was performed to study the use of ketamine as an analgesic during total intravenous anaesthesia with propofol. A comparison was made with the combination propofol/fentanyl. The propofol/ketamine combination resulted in haemodynamically stable anaesthesia without the need for additional analgesics. Postoperative behaviour was normal in all patients and none of the patients reported dreaming during or after the operation. Propofol seems to be effective in eliminating side effects of a subanaesthetic dose of ketamine in humans. We recommend the propofol/ketamine combination for total intravenous anaesthesia for surgery when stable haemodynamics are required.     

Aging prolongs recovery of psychomotor functions at emergence from propofol-alfentanil anaesthesia

PURPOSE: To compare recovery of psychomotor function in elderly and young surgical patients at emergence from propofol-alfentanil anaesthesia. METHODS: Ten elderly (> 70 yr) and 10 younger (< 40 yr) patients scheduled for orthopaedic surgery of less than three hours, were anesthetized with nitrous oxide, propofol and alfentanil. Propofol and alfentanil cumulative doses, time from cessation of propofol infusion to eye opening (EO) on verbal command and to extubation were recorded. Psychomotor performance was assessed by the Mini-Mental State (MMS) performed the day prior to surgery and postoperatively at 30, 60, and 120 min, following extubation. Propofol blood concentrations were measured at EO and at each MMS task. RESULTS: Elderly patients were comparable with young patients for preoperative MMS scores, surgery and anaesthesia duration, propofol and alfentanil cumulative doses. Postoperative MMS scores were lower at 30, 60 and 120 min, in elderly patients. Propofol blood concentrations were not different between elderly and young patients at EO, 30, 60 and 120 min. CONCLUSION: Psychomotor performance is impaired in elderly compared with young patients at emergence from propofol-alfentanil anaesthesia. These differences are not likely to be related to propofol accumulation in elderly subjects.     

Psychomotor dysfunction after remifentanil/propofol anaesthesia

BACKGROUND AND OBJECTIVES: Early recovery after anaesthesia is gaining importance in fast track management. The aim of this study was to quantify psychomotor recovery within the first 24 h after propofol/remifentanil anaesthesia using the Short Performance Test (Syndrom Kurztest (SKT)), consisting of nine subtests. The hypothesis was that psychomotor performance remains reduced 24 h after anaesthesia. METHODS: Thirty-seven patients scheduled for elective surgery took part in the study. The SKT was performed on the day before general anaesthesia (T0), 10, 30, 90 min and 24 h after extubation (T1). Parallel versions were used to minimize learning effects. Anaesthesia was introduced and maintained with remifentanil/propofol as a target controlled infusion. Propofol plasma concentration was measured 10 and 90 min after extubation. Perioperative pain management included novaminsulfon and piritramide. RESULTS: Up till 90 min after surgery and anaesthesia, psychomotor performances were significantly reduced as the lower test results in all SKT subtests indicated (P < or = 0.007 vs. baseline T0). In the three memory subtests (ST 2, ST 8 and ST 9), psychomotor performance was still reduced on the first postoperative day (P < or = 0.005; T1 vs. T0). There was no correlation between propofol plasma concentration and the psychometric test results. CONCLUSIONS: Propofol/remifentanil-based target controlled general anaesthesia for surgery is associated with a reduced psychomotor function up to the first postoperative day. Further studies are needed to confirm the usefulness of the SKT in the perioperative period and to clarify which components in the perioperative period are responsible for a lower performance in the SKT.     

Anaesthesia for laparoscopy

This is a report about five anaesthetic techniques for laparoscopy. Propofol and etomidate were used for total intravenous anaesthesia. Propofol, etomidate and thiopentone were used as induction agents prior to inhalational anaesthesia with isoflurane and nitrous oxide. Fentanyl was used for analgesia. Induction with propofol and thiopentone was rapid. Etomidate induction was characterised by myoclonus. Maintenance was smooth with inhalational anaesthesia. Of the groups that received total intravenous anaesthesia, propofol provided stable anaesthesia but required extra bolus doses. Recovery was the most rapid following total intravenous anaesthesia with propofol. Postoperative side effects were much lower after propofol. No difference was observed between the groups with regard to changes in arterial blood pressure and heart rate.     

Propofol infusion for sedation in outpatient oral surgery

An infusion of propofol was compared with intravenous boluses of diazepam as sedation for minor oral surgery under local anaesthesia in 12 healthy patients who had elective bilateral surgical extraction of lower third molars; the patients served as their own controls. Plasma catecholamine, vasopressin and cortisol concentrations were determined from repeated blood samples. The total administered dose of propofol was 3.93 (SD 1.34) mg/kg and of diazepam 0.28 (SD 0.07) mg/kg. No cardiovascular depression or airway problems occurred. Other side effects were also rare but some discomfort on injection was frequent with propofol. Recovery times were faster after propofol than after diazepam as assessed by the Maddox wing and visual analogue scales. Propofol also provided better amnesia compared to diazepam at the time of the extraction of the teeth. Eight of the 12 patients subjectively preferred propofol sedation. There was no hormonal stress response in either group.     

Anaesthesia for computerised tomography of the brain in children: a comparison of propofol and thiopentone

Propofol (2,6-di-isopropylphenol) 1.5-2.0 mg/kg i.v. was compared with thiopentone 3.0-4.0 mg/kg i.v. as an induction agent in anaesthesia for computerised tomography (CT) of the brain in children. Both induction agents were combined with diazepam 0.2 mg/kg i.v. Thirty children (ASA physical status I-II) aged 3 to 10 years and scheduled for elective examination were included in the randomized study. The haemodynamic response to propofol and thiopentone did not differ between the groups. Spontaneous respiration was retained in all patients and no ventilatory support was required during anaesthesia. The incidence of side-effects did not differ between the groups. Pain on injection with propofol was rare (n = 1) after mixing 1 ml lignocaine (1%) with propofol prior to induction. The recovery times were significantly shorter in the propofol than in the thiopentone group. Propofol appears to be a promising alternative for use in short day-case anaesthesia for CT scanning in children.     

General versus regional anaesthesia for cataract surgery: effects on neutrophil apoptosis and the postoperative pro-inflammatory state

At clinically relevant concentrations, volatile anaesthetic agents influence neutrophil function. Our hypothesis was that sevoflurane would inhibit neutrophil apoptosis and consequently influence the postoperative pro-inflammatory state. In order to identify selectively the effect of the anaesthetic agent sevoflurane, we studied patients undergoing minimally stimulating (cataract) surgery randomly allocated to receive either sevoflurane (n = 11) or local anaesthesia (n = 12). Venous blood samples were taken immediately prior to anaesthesia and at 1, 8 and 24 h thereafter. The rate of neutrophil apoptosis, plasma concentration of cytokines and differential white cell count were measured. The rates of neutrophil apoptosis and plasma concentrations of IL-1beta, TNF-alpha and IL-8 at each time point were similar in the two groups. IL-6 concentrations increased significantly and to a similar extent compared to preanaesthetic levels at 8 and 24 h. This study demonstrates that sevoflurane does not influence the rate of neutrophil apoptosis, cytokine concentrations and neutrophil count following cataract surgery.     

Activation of the electrocorticogram by propofol during surgery for epilepsy

Propofol is used widely during general anaesthesia but there has been concern that it may be implicated in provoking seizure activity. We have investigated the effects of low-dose propofol on the electrocorticogram of anaesthetized patients undergoing surgery for medically intractable epilepsy. During continuous peroperative recording of the electrocorticogram, propofol was administered in 25 mg increments until burst suppression occurred. Activation of the electrocorticogram occurred in 17 of 20 patients. There was an increase in mean spike frequency in 16, extension of spike distribution in 15 and polyphasia in 13 patients. The mean dose of propofol required to cause burst suppression was 88.2 (range 25-175) mg. We conclude that at low doses, propofol caused activation of the electrocorticogram in epileptic patients but at higher doses burst suppression was induced.      

Effect of propofol and isoflurane anaesthesia on the immune response to surgery

There are two major subpopulations of peripheral helper T lymphocytes: T helper 1 (Th1) and T helper 2 (Th2) cells. Surgical stress increases the number of Th2 cells, and decreases that of Th1 cells, resulting in a decrease in the Th1/Th2 ratio, and, consequently, in suppressed cell-mediated immunity. Since anaesthesia can suppress the stress response to surgery, it may inhibit the decrease in the Th1/Th2 ratio. Using flow cytometry, we studied whether propofol anaesthesia (n = 9) or isoflurane anaesthesia (n = 9) had more effect on the decrease in the Th1/Th2 ratio after surgery in patients undergoing craniotomy. The Th1/Th2 ratio decreased significantly after isoflurane anaesthesia (p = 0.011), while it did not change after propofol anaesthesia. The ratio was significantly lower with isoflurane than propofol (p = 0.009). Propofol anaesthesia attenuated the surgical stress-induced adverse immune response better than isoflurane anaesthesia.     

Tissue antioxidant capacity during anesthesia: propofol enhances in vivo red cell and tissue antioxidant capacity in a rat model.

The effects of anesthesia on ischemia-reperfusion injury are of considerable scientific and clinical interest. We examined the effects of propofol (known to possess antioxidant activity) and halothane (devoid of antioxidant activity in vitro) on tissue and red blood cell (RBC) antioxidant capacity. Adult male Wistar rats were anesthetized with halothane 0.5%-1.0% (n = 7), propofol 500 microg x kg(-1) x min(-1) with halothane 0.25%-0.5% (small-dose propofol; n = 9), or propofol 2000 microg x kg(-1) x min(-1) (large-dose propofol; n = 8) for 45 min. Blood and tissue samples of liver, kidney, heart, and lung were then harvested for in vitro exposure to a peroxidizing agent. Red cell malondialdehyde and tissue thiobarbituric acid reactive substances were determined spectrophotometrically. Antioxidant capacities of blood and tissues in the Large-Dose Propofol group, and of blood and all tissues except lung in the Small-Dose Propofol group, were increased significantly compared with halothane (P < 0.003). The increases in tissue antioxidant capacities varied in their magnitude: RBC > liver > kidney > heart > lung. There was a high correlation between changes in RBC susceptibility to oxidative damage and corresponding changes in tissues. These findings demonstrate that large-dose propofol significantly enhances tissue antioxidant capacity, and RBC antioxidant capacity can serve as a functional measure of tissue activity, in vivo. IMPLICATIONS: We designed this study to investigate the antioxidant effects of propofol in various tissues in a rat model. Pretreatment of animals with propofol led to a reduction in the susceptibility to an in vitro oxidative stress of five different tissues investigated, demonstrating the drug's ability to limit oxidative injury. This may have future application in limiting organ dysfunction after periods of tissue ischemia (which results in oxidative damage).     

Propofol sedation in total knee replacement

Purpose

This study aimed to show the effect of propofol sedation on oxidative stress and inflammation resulting from ischemia-reperfusion.

Methods

After having obtained written informed consent from the patients and ethics committee approval, 36 patients were randomly allocated to 2 groups: group C, control and group P, propofol. Spinal anesthesia was administered to both groups with 15 mg bupivacaine. Patients in group P received a propofol infusion of 2 mg/kgBW/h and the patients in group C received a placebo infusion in an equal dose. Malondialdehyde (MDA), superoxide dismutase (SOD) and the total antioxidative capacity (TAC) levels were measured in venous blood samples prior to propofol or placebo administration (preischemia T0), 30 min after placing the tourniquet (ischemia T1) and 2 h after deflation of the tourniquet (reperfusion T2). High sensitivity C-reactive protein (hsCRP) and neutrophil levels were measured before propofol was administered (T0) and 12 h after reperfusion (T3).

Results

While serum MDA and SOD levels were significantly higher during the reperfusion period than the preischemic period, TAC levels were found to be low in the control group (p?<?0.05). In the propofol group there were no differences between the preischemia-reperfusion periods with respect to MDA, SOD and TAC levels (p?>?0.05). The neutrophil and hsCRP levels were observed to be increased to a lesser extent in the propofol group compared to the control group (p?<?0.05).

Conclusions

Propofol infusion in addition to spinal anesthesia may reduce oxidative damage and the inflammatory response developing due to the tourniquet in total knee replacement surgery.     

The effect of anaesthetic technique during primary breast cancer surgery on neutrophil–lymphocyte ratio,platelet–lymphocyte ratio and return to intended oncological therapy

Inflammation and immunosuppression contribute to the pathogenesis of cancer. An increased neutrophil–lymphocyte ratio reflects these processes and is associated with adverse cancer outcomes. Whether anaesthetic technique for breast cancer surgery influences these factors, and potentially cancer recurrence, remains unknown. We conducted a secondary analysis in patients enrolled in an ongoing trial of anaesthetic technique on breast cancer recurrence. The primary hypothesis was that postoperative neutrophil–lymphocyte ratio is lower in patients allocated to receive propofol‐paravertebral rather than inhalational agent‐opioid anaesthesia for primary breast cancer surgery. Among 397 patients, 116 had differential white cell counts performed pre‐operatively and postoperatively. Pre‐operative neutrophil–lymphocyte ratio was similar in the propofol‐paravertebral 2.3 (95%CI 1.8–2.8) and inhalational agent‐opioid anaesthesia 2.2 (1.9–3.2) groups, p = 0.72. Postoperative neutrophil–lymphocyte ratio was lower (3.0 (2.4–4.2) vs. 4.0 (2.9–5.4), p = 0.001) in the propofol‐paravertebral group. Propofol‐paravertebral anaesthesia attenuated the postoperative increase in the neutrophil‐lymphocyte ratio.     

Total intravenöse Anästhesie

Since venous cannulation in children has become easier and extensive experience has been gained with total intravenous anaesthesia (TIVA) in adults, the interest in TIVA for children has recently increased. An intensified sensitivity of the operating room atmosphere to contamination with volatile anaesthetic agents is another important reason to choose intravenous techniques for paediatric anaesthesia. One of the most interesting agents for TIVA in paediatric anaesthesia is propofol. The pharmacokinetic and pharmacodynamic data for modern intravenous drugs is poor. Because the interpatient variability is relatively large, pharmacokinetic data can only provide guidelines for the dosage of propofol. Propofol has a rapid and smooth onset of action and is as easy to titrate in children as in adults. Propofol can be excellently controlled. Severe haemodynamic side-effects are missing in healthy children and plasma is cleared rapidly of propofol by redistribution and metabolism. There is no evidence of significant accumulation, not even after prolonged infusion times. Because propofol has no analgetic properties it must be combined with analgetics or a regional block for all painful procedures. The combination with the ultra-short acting remifentanil is a major advantage, but requires effective analgetic concepts for painful procedures. In comparison the combination of propofol with long acting opioids abolishes some of the favourable properties of propofol. Further studies of the kinetics and dynamics of propofol and other intravenous agents are needed in paediatrics which should focus on age, maturity and severity of illness. The whole importance of the propofol-infusion syndrome has to be cleared up urgently. TIVA has an important significance in paediatric anaesthesia for diagnostic and therapeutic procedures, especially where these have to be repeated. In day-case anaesthesia TIVA has advantages for all short procedures and for ENT and ophthalmic surgery: even after prolonged infusion children have an short recovery time. There is no evidence of agitation or other behavioural disorders after TIVA with propofol in paediatric anaesthesia. Propofol has anti-emetic properties. TIVA with propofol can be combined with regional anaesthesia advantageously to provide long-lasting analgesia after surgery. TIVA with propofol has been used successfully for sedation of spontaneously breathing children for MRI and CT and other procedures with open airways like bronchoscopy or endoscopy. Propofol facilitates endotracheal intubation without the use of muscle relaxants. Of course, in malignant hyperthermia TIVA will continue to be the technique of choice. Nothing is known about awareness under TIVA in paediatric patients. TIVA must be considered by comparison with the volatile agents. The use of ultra-short acting agents may cause problems such as awareness, vagal response, involuntary movements and in some cases slow recovery after prolonged infusion of propofol. But it is not known exactly how often this happens during paediatric anaesthesia. With TIVA an effective postoperative analgesia must be provided. Newer administration techniques such as the target-controlled infusions or closed-loop control systems are under development and will help to minimise the potential risk of overdosage with TIVA in paediatrics. At the present TIVA is an interesting and practicable alternative to volatile anaesthesia for pre-school and school children. TIVA with propofol in infants younger than 1 year old requires extensive experience with TIVA in older children and with the handling of this special age group and should be undertaken with maximum precautionary measures.     

Visual experiences during cataract surgery: what anaesthesia providers should know

Recently published literature shows that most patients experience a variety of visual sensations during cataract surgery under local anaesthesia. Most patients (80-100%) retain at least some light perception in the operated eye and many also experience a variety of other visual sensations during cataract surgery under regional ophthalmic anaesthesia (retrobulbar, peribulbar and sub-Tenon's blocks) or topical anaesthesia. The visual sensations experienced include perception of movements, flashes, colours, changes in brightness, or the sight of surgical instruments, the surgeon's hands or fingers, or even the surgeon. These findings are clinically significant because 3-16.2% of patients who had cataract surgery under either regional or topical anaesthesia were frightened by their intraoperative visual experience. Fear and anxiety may cause some patients to become uncooperative during the surgery and may also induce a sympathetic stress response that might cause hypertension, tachycardia with myocardial ischaemia, hyperventilation or an acute panic attack. These effects are especially undesirable as the majority of cataract patients are elderly and have concurrent medical problems. Besides increasing the risk of intraoperative complications, a frightening visual experience may decrease patient satisfaction. Appropriate preoperative counselling has been shown to be effective in reducing the patients' fear. As most patients retain some visual function during cataract surgery under local anaesthesia, anaesthesia providers should be mindful of this phenomenon and offer appropriate preoperative information and counselling to their patients.     

Neutrophils from patients undergoing hip surgery exhibit enhanced movement under spinal anaesthesia compared with general anaesthesia

The purpose of this research was to investigate whether the effects of regional anaesthesia on neutrophil migration differ from those due to general anaesthesia during major orthopaedic surgery in human patients. Eighteen patients underwent spinal or general anaesthesia (halothane or isoflurane) for surgery (six patients in each group). Blood samples were taken prior to induction of anaesthesia and after surgery was in progress for one hour. The movement of isolated neutrophils was measured in both samples in the chemotactic chamber toward lipopolysaccharide activated pooled serum. In addition plasma concentrations of catecholamines were determined in the blood samples. Neutrophils extracted from peripheral blood during spinal anaesthesia and surgery moved further towards a complement-derived attractant than neutrophils obtained from patients undergoing surgery under general anaesthesia with halothane or isoflurane and surgery (156.4 +/- 7.6 microns vs 114.3 +/- 6.1 microns or 119 +/- 8.4 microns respectively, P < 0.05). Increased concentrations of adrenaline were present in both general anaesthetic groups whereas the spinal group had lower concentrations than those prior to anaesthesia and surgery. It is considered unlikely that these differences in neutrophil reactivity are due to the direct effects of anaesthetic agents employed. The effects are likely to be the result of differing effects of spinal anaesthesia on the stress response or immunological mediators.     

Heart block following propofol in a child

We present the case of a nine-year-old boy afflicted with Ondine's curse, who developed complete atrioventricular heart block after a single bolus of propofol for induction of anaesthesia for strabismus surgery. Ondine's curse, the other name for congenital central hypoventilation syndrome, is characterized by a generalized disorder of autonomic function. Propofol has no effect on the normal atrioventricular conduction system in humans but it reduces sympathetic activity and can highly potentiate other vagal stimulation factors. Heart block has been documented after propofol bolus use in adults but, to our knowledge, not in children. It would appear that propofol is not a good choice for anaesthesia in congenital central hypoventilation syndrome.     

Effects of propofol on guinea pig respiratory smooth muscle

The effects of propofol on the tone of guinea pig respiratory smooth muscle was studied both in vitro and in vivo. In vitro, the activity of propofol on tracheal smooth muscle was investigated using a force displacement transducer for isometric tension responses. Isoproterenol was used as the control. Concentration-response curves to propofol and isoproterenol were obtained using a cumulative dose schedule. Propofol (0.32–10.24 μg·ml⁻¹) relaxed the tracheal smooth muscle in a concentration-dependent manner, but was less potent than isoproterenol (equipotent molar ratio 29 000∶1). This effect of propofol was not affected by prior administration of atropine, propranolol, prazocin, or yohimbine, and it did not appear to be mediated via calcium antagonism. The solvent for propofol (10% intralipid) had no effect on the tracheal smooth muscle in vitro. The in vivo study measured the effect of propofol on lung pressure in deeply anesthetized guinea pigs using histamine induced bronchoconstriction. Propofol (1–4.5 mg·kg⁻¹, i.v.) exhibited neither relaxant nor constrictor effects. It is possible that the effects of propofol observed in vitro are due to nonspecific action, while the finding of no effect in vivo could be due to different tissue sensitivity to propofol, i.e., tracheal smooth muscle may be more responsive than bronchial smooth muscle. Propofol does not seem to have any deleterious effects on airway smooth muscle.     

Hemodynamics, hemocoagulation and neuroendocrine responses in long-duration anesthesia. Comparison of propofol infusion with thiopentone and NLA II

Ten patients receiving propofol for the induction and maintenance of anaesthesia were compared with 10 patients in whom anaesthesia was induced with thyopentone and maintained with fentanil. The cardiovascular response to anaesthesia, the effects on coagulation and fibrinolysis and the neuroendocrine response have been investigated during surgical procedures exceeding 90'. There was a larger decrease in PA after induction in the propofol group versus control, but the overall quality of anaesthesia during induction and maintenance was comparable in both groups. No differences were found about blood coagulation and fibrinolysis between the groups. Important differences between the groups were instead found about the cortisol response to anaesthesia and surgery: in the propofol group there was a decrease in the cortisol concentration in 90' sample with no statistical significance, returning to the baseline value after 1 h from recovery. In the control group a significant increase of cortisol concentration was noted both at 90' and 1 h after the end of anaesthesia.