Influence of anaesthesia and muscle relaxation on intubating conditions and sympathoadrenal response to tracheal intubation

Background : The study aimed to assess the relative influence of anaesthesia and muscle relaxation on intubating conditions and the haemodynamic and catecholamine responses to tracheal intubation.
Methods : Sixty ASA 1 or 2 patients were randomly assigned to one of four groups (15 patients each) that differed in the depth of anaesthesia (thiopentone plus fentanyl 2.5 μg kg^-1 or thiopentone alone) and the degree of vecuronium–induced neuromuscular block (100% or _>: 65%) at intubation. Muscle relaxation was measured at 0.1 Hz by means of mechanomyography. Heart rate (HR) and mean arterial blood pressure (MAP) were measured before and after induction of anaesthesia, and 1 min and 5 min following intubation, while adrenaline (A) and noradrenaline concentrations (NA) were determined from arterial blood samples.
Results : Intubating conditions were improved primarily by providing complete muscle relaxation at the adductor pollicis muscle (P<0.001) and to a lesser extent by adding fentanyl to thiopentone (P=0.04). The response of HR and MAP to tracheal intubation was attenuated mainly by fentanyl (P<0.001). Complete muscle relaxation further diminished the response of MAP to intubation (P=0.03). Changes in A and NA were dependent on the depth of anaesthesia only (P =>0.01).
Conclusion : The results of the study demonstrate that the sympathoadrenal response to intubation is attenuated by adding fentanyl (2.5 kg^-1) to an induction regimen with thiopentone, whereas provision of complete muscle relaxation at the adductor pollicis muscle is necessary to attain smooth intubating conditions.     

Intubating conditions provided by propofol and alfentanil - acceptable, but not ideal

Background: The use of muscle relaxants to facilitate intubation is associated with several side effects regardless of whether depolarizing or non-depolarizing drugs are used. In the present study we compared the intubating conditions, haemodynamic responses and changes in oxygen saturation following induction with alfentanil and propofol or alfentanil, thiopental and suxamethonium.
Methods: Eighty patients (ASA I or II) were in a double-blind manner assigned to receive either of the two induction methods. Intubating conditions were assessed on the basis of jaw relaxation, ease of insertion of the endotracheal tube and coughing on intubation. Heart rate, systolic arterial pressure and oxygen saturation were monitored throughout the procedure.
Results: The use of alfentanil and propofol resulted in significantly lower scored intubation points. Systolic arterial pressure decreased and heart rate increased significantly in the alfentanil-thiopental-suxamethonium group as compared to the alfentanil-propofol group. There were no significant changes in oxygen saturation.
Conclusion: The results show that propofol and alfentanil in combination provides haemodynamic stability and unaltered oxygen saturation but less optimal intubating conditions.     

丙泊酚、硫喷妥钠联合麻醉诱导对血液动力学的影响

目的：观察小剂量丙泊酚和硫喷妥钠联合用于麻醉诱导对血流动力学的影响及临床应用价值。方法：择期全身麻醉气管插管手术患者84例，ASAⅠ-Ⅱ级，随机分成3组（n=28），硫喷妥钠组（A组）：诱导量5mg/kg；丙泊酚组（B组）；诱导量2.0mg/kg；联合诱导组（C组）硫喷妥钠1－2mg/kg加丙泊酚0.5-1.0mg/kg，观察诱导后2min,5min,10min血液动力学变化。结果：C组在丙泊酚诱导前先静脉预注硫喷妥钠1－2mg/kg，患者静脉注射部位疼痛发生率明显低于B组（P＜0．01），平均动脉压和心率均无明显变化（P＞0．05），而A和B组给药后2min与5min平均动脉压均低于麻醉前，心率均高于麻醉前（P＜0．05－P＜0．05）。结论：丙泊酚与硫喷妥钠联合麻醉诱导具有协同作用，减少单独用药不良反应发生率，血液动力学稳定，麻醉诱导更加平稳，安全，为临床全麻诱导提供一种可行的方法。     

Growth of Escherichia coli in propofol, lidocaine, and mixtures of propofol and lidocaine

BACKGROUND: Microorganisms grow rapidly in propofol. Extrinsic contamination of propofol is thought to be a source of postoperative sepsis and wound infection. We studied growth of a strain of Escherichia coli in thiopental, propofol, lidocaine, and mixtures of propofol and lidocaine. METHODS: The pathogen was exposed to 2.5% thiopental; 1.0% propofol; 1.0%, 2.0% and 4.0% preservative-free lidocaine; and propofol solutions containing 0.25%, 0.5%, 1.0%, 2.0%, or 4.0% lidocaine for 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, and 24 h at room temperature, respectively. The inocula from these suspensions were cultured for 48 h at 37 degrees C after the antimicrobial activity of the local anesthetics in the inocula was inactivated by a 1:1000 dilution with distilled water. RESULTS: No organisms grew after exposure to 2.5% thiopental. The exposure of E. coli to propofol increased the colony count to approximately 90 times the control count. The colony counts of E. coli after exposure to 1.0%, 2.0% and 4.0% lidocaine and 0.25%, 0.5%, 1.0%, 2.0% and 4.0% lidocaine in 1.0% propofol were lower than the counts after exposure to 1.0% propofol (P = 0.0048, 0.0027, 0.0003, 0.0503, 0.0188, 0.0080, 0.0044, and 0.0001, respectively). The growth rate of the microorganism was significantly higher in cultures exposed to 1.0% propofol than that in cultures exposed to lidocaine alone or lidocaine-propofol mixtures (P < 0.0001, respectively). CONCLUSION: Lidocaine possesses bacteriostatic activity against E. coli. Addition of lidocaine to propofol confers its bacteriostatic activity to the mixture and may decrease the hazard of infection associated with the extrinsic contamination of propofol.     

Effect of atmospheric ammonia on mortality rate of rats with barbiturate intoxication

Ammonia inhalation (0.84–1.07 mg/liter, 3 h) was accompanied by a 65% increase in ammonia concentration in mixed blood of intact rats. This treatment did not cause death of intact animals, but potentiated the lethal effect of sodium thiopental and inhibited external respiration and O₂ consumption in animals. The resistance of rats to the lethal effect of barbiturate tended to decrease under conditions of experimental hyperammonemia induced by intraperitoneal injection of ammonium acetate in a nonlethal dose (6 mmol/kg). Our results indicate that potentiation of the toxic effect of barbiturates by atmospheric ammonia is related to its resorptive effects. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 143, No. 6, pp. 634–636, June, 2007     

Sevoflurane anaesthesia in children after induction of anaesthesia with midazolam and thiopental does not cause epileptiform EEG

Background. Sevoflurane is a methyl ether anaesthetic commonlyused for induction and maintenance of general anaesthesia inchildren. Sevoflurane is a non-irritant and acts quickly soinduction is usually calm. However, inhalation induction withhigh concentrations of sevoflurane can cause convulsion-likemovements and seizure-like changes in the electroencephalogram(EEG). Little is known about the EEG during maintenance of anaesthesiawith sevoflurane, so we planned a prospective trial of sevofluranemaintenance after i.v. induction with benzodiazepine and barbiturate,which is another common induction technique in children. Methods. EEG recordings were made before premedication withmidazolam (0.1 mg kg^–1 i.v.), during induction ofanaesthesia with thiopental (5 mg kg^–1), and duringmaintenance with sevoflurane (2% end-tidal concentration inair/oxygen without nitrous oxide) in 30 generally healthy, 3-to 8-year-old children having adenoids removed. Noise-free EEGdata of good quality were successfully recorded from all 30children. Results. Two independent neurophysiologists did not detect epileptiformdischarges in any of the recordings. Conclusion. Premedication with midazolam, i.v. induction withthiopental and maintenance of anaesthesia with 2% sevofluranein air does not cause epileptiform EEG patterns in children. Br J Anaesth 2002; 89: 853–6     

Pharmacodynamic modeling of thiopental anesthesia

We have pharmacodynamically modeled the relationship between the thiopental serum concentration and its effects on the electroencephalogram (EEG). Power spectral analysis was used to calculate the spectral edge, a measure of the underlying EEG frequency that characterizes the progressive slowing of the EEG induced by thiopental. Eight male volunteer subjects had venous thiopental serum concentrations measured, and 10 surgical patients had arterial serum concentrations measured. Thiopental was infused at a rate of 75 to 150 mg/min until a burst suppression EEG pattern was evident. Frequent blood samples were obtained during and after the infusion for measurement of serum thiopental concentrations, and the EEG was recorded for subsequent off-line power spectral analysis to calculate the spectral edge. With venous blood sampling, it was not possible to demonstrate significant hysteresis between the thiopental serum concentration and the spectral edge, allowing thiopental concentrations to be directly related to the spectral edge. With arterial blood sampling, significant hysteresis was present, requiring an effect compartment to relate concentration to effect. The half-time for equilibration (mean ± SD) between concentration and response for the arterial data was 1.2± 0.30min. This value for K_eo is consistent with known values for cerebral blood flow and thiopental brain: blood partition coefficient. Arterialvenous concentration differences cause the apparent lack of hysteresis with venous blood sampling. An inhibitory sigmoid E _max pharmacodynamic model optimally characterized the relationship between thiopental concentrations and the spectral edge. This model allows estimation of the thiopental serum concentration that causes one-half of the maximal EEG slowing (IC₅₀), which is a measure of an individual's sensitivity to thiopental. Except for the hysteresis, there was no statistical difference in the parameters of the inhibitory sigmoid E _max pharmacodynamic model when venous and arterial blood samplings were compared. Arterial blood sampling offers some distinct advantages when pharmacodynamically modeling continuous, rapidly changing measures of drug effect, such as the EEG.This work was supported by NIH Grant R23-GM28032, NIA Grant P01-AG03104, the Veterans Administration Research Service, and the Anesthesiology/Pharmacology Research Foundation of Palo Alto, California. Dr. Hudson was supported by the Medical Research Council of Canada.     

Midazolam does not potentiate the effect of vecuronium in patients

Reports of midazolam interaction with vecuronium in animals prompted us to compare midazolam (0.25 mg kg-1) with thiopentone (5 mg kg-1) for possible interactions with vecuronium in patients, when used for induction of anaesthesia. After the administration of either of the two induction agents, the patients received vecuronium 0.1 mg kg-1. The onset time, duration of action and 25-75% recovery index of the neuromuscular blockade were recorded by measuring the force of thumb adduction evoked by ulnar nerve stimulation. We found no differences between patients receiving either midazolam or thiopentone in their response to vecuronium. In three of the ten patients receiving midazolam, the injection of this drug produced a 8-29% reduction of the initial twitch height.     

Anoxic depolarization of rat hippocampal slices is prevented by thiopental but not by propofol or isoflurane

Background. There is strong evidence to suggest that anoxicdepolarization (AD) is an important factor in hypoxia/ischaemia-inducedneural damage. Treatments that prevent the occurrence of ADmay be useful in providing neuronal protection against hypoxia.The current study was designed to determine whether generalanaesthetics which have been suggested to ‘induce prophylaxis’against hypoxia can attenuate the incidence of AD. Methods. The effects of anoxia (3 min) on evoked extracellularlyrecorded field potentials of CA1 neurons in rat hippocampalslices were assessed in the absence and presence of the i.v.general anaesthetics thiopental and propofol and the volatileanaesthetic isoflurane. Results. In the absence of anaesthetics, AD occurred in 81%of the preparations tested. Thiopental (2x10^–4 M) significantlyreduced the incidence of AD (16%, P=0.0006). In comparison,propofol (2x10^–4 M) and isoflurane (1.5 vol%) were ineffective(69% and 60%, respectively). Furthermore, in the presence ofthiopental, the population spike amplitude recovered with andwithout AD (90% and 94% of pre-anoxic value, respectively) following3 min anoxia. Conclusion. The prophylactic effect of thiopental against hypoxiamight be induced, in part, by preventing the generation of AD.     

Pharmacological effects of intravenous melatonin: comparative studies with thiopental and propofol

Background. Possible utility of high-dose i.v. melatonin asan anaesthetic adjuvant has not been studied. This study comparedits effects with thiopental and propofol. Methods. Sprague Dawley rats were assigned to receive bolusor cumulative i.v. doses of melatonin, thiopental or propofol.Righting reflex, hindpaw withdrawal to a noxious stimulus, responseto tail clamping and haemodynamic effects were assessed. Results. Melatonin caused a dose-dependent increase in paw withdrawalthreshold and the percent of rats displaying loss of the rightingreflex. Melatonin was comparable to thiopental and propofolin terms of its rapid onset of hypnosis. The mean ED₅₀ valuesfor loss of righting reflex were 5.4 (SEM 1.2), 12.5 (1.1) and178 (1.1) mg kg^–1 for propofol, thiopental and melatonin,respectively. The percent of rats displaying loss of responseto tail clamping was greater with propofol than with melatonin(P<0.05). Haemodynamic changes produced by melatonin or propofolwere similar in onset and magnitude. Conclusions. I.V. melatonin can exert hypnotic effects similarto those observed with thiopental and propofol. Melatonin exhibitedsignificant antinociceptive effects but was less effective inabolishing the response to tail clamping. Br J Anaesth 2003; 90: 504–7