The postantibiotic effect of azithromycin on respiratory pathogens

We assessed the post-antibiotic effect (PAE) of azithromycin against 3 strains of Streptococcus pneumoniae 2 strains of Haemophilus influenzae and 2 strains of Moraxella catarrhalis. The strains were exposed for 2 hours to a concentration of 0.5 mg/l. A stationary phase inoculum of 1 x 10(6)-5 x 10(6) CFU/ml in IsoSensitest Broth with 5% lysed horse blood and 20 mg/l NAD was used and shaken for the duration of the experiment. Antibiotic was neutralised by dilution 1:1000 into pre-warmed medium. [table: see text] In conclusion, even at such low concentration as achieved in serum, azithromycin has a PAE against the respiratory pathogens studied. In our opinion this could allow the use of azithromycin, in the usual regimen even in bacteremic respiratory infections.     

Influence of volatile anaesthetics on hypercapnoeic ventilatory responses in mice with blunted respiratory drive

Background. Subanaesthetic concentrations of volatile anaestheticssignificantly affect the respiratory response to hypoxia andhypercapnoeia. Individuals with an inherited blunted respiratorydrive are more affected than normal individuals. To test thehypothesis that subjects with blunted hypercapnoeic respiratorydrive are diversely affected by different anaesthetics, we studiedthe effects of three volatile anaesthetics on the control ofbreathing in C3H/HeJ (C3) mice, characterized by a blunted hypercapnoeicrespiratory response. Methods. Using whole body plethysmography, we assessed respiratoryrate (RR) and pressure amplitude in 11 male C3 mice at rest,during anaesthesia with isoflurane, sevoflurane or desflurane,and during recovery. To test respiratory drive, mice were exposedto 8% carbon dioxide. Data were analysed by two-way-analysisof variance with post hoc tests and Bonferroni correction. Results. RR was unaffected during sevoflurane anaesthesia upto 1.0 MAC. Likewise, sevoflurane at 1.5 MAC affected RR lessthan either isoflurane (P=0.0014) or desflurane (P=0.0048).The increased RR to a carbon dioxide challenge was blocked byall three anaesthetics even at the lowest concentration, andremained depressed during recovery (P<0.0001). Tidal volumewas unaffected by all three anaesthetics. Conclusions. In C3 mice, spontaneous ventilation was less affectedduring sevoflurane compared with either isoflurane or desfluraneanaesthesia. However, the RR response to hypercapnoeia was abolishedat 0.5 MAC for all the anaesthetic agents and remained depressedeven at the end of recovery. Our data suggest that differentvolatile anaesthetics have varying effects on the control ofbreathing frequency but all block the respiratory response tocarbon dioxide. Therefore, a genetic predisposition to a bluntedcarbon dioxide response represents a susceptibility factor thatinteracts with hypercapnoeic hypoventilation during maintenanceof anaesthesia and in the emergence from anaesthesia, regardlessof the agent used. Br J Anaesth 2004; 92: 697–703     

Pharmacology of modern volatile anaesthetics

The volatile anaesthetics sevoflurane and desflurane feature new and promising properties. Their low blood and tissue solubility enables rapid onset of and emergence from anaesthesia, thus enhancing patient safety and comfort. This article is designed as an up-to-date review of the pharmacokinetic and pharmacodynamic properties of modern volatile anaesthetics. The first part focuses on pharmacokinetic issues such as substance properties, uptake and elimination. The second part covers the effects of inhaled anaesthetics on organ systems, with emphasis on the central nervous system, the cardiovascular system, the respiratory tract, liver and kidneys.     

Illicit use of modern volatile anaesthetics

Sixteen reported cases of abuse of modern volatile anaesthetics are summarized. Twelve of the sixteen subjects died. Halothane was ingested or injected intravenously for suicidal purpose, and sniffed for mood elevation. Abuse of modern volatile anaesthetics deserves more attention than it has received in the past.     

Uptake of volatile anaesthetics in children

The uptake of halothane is known to be more rapid in children than in adults, but comparable clinical data regarding other inhalational anaesthetics are not available. In this study, the rates of uptake of halothane, enflurane, isoflurane and methoxyflurane were compared in children of different ages. Expired (FE') and inspired (FI) vapour concentrations were measured with an infrared analyser, and FE'/FI ratios were used to determine rates of uptake. Uptake rates of halothane, enflurane and methoxyflurane were more rapid in the younger than in the older children, but age had no effect on the uptake of isoflurane which was uniformly rapid in all the children studied.     

The effect of inhalational anaesthetics on QTc interval

BACKGROUND AND OBJECTIVE: The aim of this study was to assess time dependent cumulative effects of three different inhalation anaesthetics on QTc interval during the maintenance of anaesthesia. METHOD: Seventy-five ASA I-II male patients undergoing inguinal herniorrhaphy were randomly allocated into three groups. No premedication was given. Anaesthesia was induced with thiopental and tracheal intubation was facilitated by vecuronium in all groups. Anaesthesia was maintained with 0.8% halothane (Group I) (n = 25), 1% isoflurane (Group II) (n = 25), or 2% sevoflurane (Group III) (n = 25) and 66% nitrous oxide in oxygen. Three lead electrocardiogram recordings were taken before induction, 2, 5, 10, 15, 30 and 45 min after induction and after extubation. Heart rate, systolic, diastolic, mean arterial pressure and SpO2 were recorded at the same time. Heart rate and corrected QT interval were evaluated by using Bazett's formula. Multivariate analysis of variance for repeated measures was used to determine intergroup and intragroup differences. RESULTS: There was no statistically significant difference in the baseline QTc values of the groups. There was no difference between QTc values with halothane and sevoflurane. There was a difference between QTc values with isoflurane and those with the other two inhalation anaesthetics (P < 0.05). Although QTc values in the isoflurane group were higher at all times, the critical value of 440 ms was not exceeded. CONCLUSION: We conclude that halothane 0.8%, isoflurane 1% and sevoflurane 2% do not prolong QTc interval.     

The cerebral protective effect of anaesthetics

The concept of cerebral protection refers to any prophylactic measure initiated before an ischaemic insult to improve the tolerance of the central nervous system to that insult. Theoretical strategies for protecting the brain proceed from pathophysiology and rely on both the metabolic and biochemical theories. Decreasing cerebral metabolism and, more importantly, preventing the cascade of biochemical events consecutive to cerebral ischaemia are central to this process. This article will consider the potential neuroprotective effect of anaesthetic agents. The tolerance to ischaemia appears to be better during anaesthesia than during the awake state. According to basic studies and experimental data, most of the anaesthetic agents share interesting properties consistent with the potential mechanisms of cerebral protection. However, experimental success does not automatically result in clinical benefit. Although cerebral protection seems to depend more on specific drugs and techniques, it cannot be concluded that anaesthetic agents play a substantial role as first choice adjuvants. Answering that question and defining the modalities of a neuroprotective anaesthetic is an exciting challenge for the future.     

Murine auto- and cross-tolerance to volatile anaesthetics

Auto-tolerance and cross-tolerance to halothane, isoflurane and enflurane were tested on 36 mice divided into three equal groups. Each group was first exposed to increasing concentrations of either of the three anaesthetics on 13 occasions. The concentration at which each mouse lost its righting reflex during successive exposures in a rotating cage was noted. Cross-tolerance was assessed by comparing the number of mice which had lost their righting reflexes during their first exposure to a given anaesthetic agent to the number which lost it after having been exposed to another anaesthetic. All animals developed auto-tolerance to halothane, isoflurane and enflurane. Cross-tolerance was noted only between mice exposed to isoflurane and enflurane and between mice exposed to halothane and subsequently anaesthetized with isoflurane, but not vice versa.     

The variable effect of low-dose volatile anaesthetics on the acute ventilatory response to hypoxia in humans: a quantitative review

The purpose of this study was to review published studies (identified by a Medline-assisted search) on the effect of < or = 0.2 minimal alveolar concentration (MAC) halothane, isoflurane, enflurane and sevoflurane on the acute hypoxic ventilatory response in healthy subjects. Each article was examined for the anaesthetic agent, speed of hypoxic stimulus, background carbon dioxide and subject stimulation (audiovisual or painful). Analysis of variance was used to assess the significance of the influence of each of these factors on the standardised hypoxic response (the acute hypoxic ventilatory response in l.min(-1) in the presence of anaesthetic, expressed as a fraction of the response without anaesthetic). There were 37 separate studies within 21 published articles. The main factor influencing standardised hypoxic response was anaesthetic agent (p < 0.002). A second influential factor was subject stimulation (p < 0.014), but the interaction term of agent and stimulation was also significant (p < 0.039), suggesting that the influence of stimulation varied with the agent used. Speed of hypoxia and background carbon dioxide had no influence. In contrast to previous authors' assertions that study conditions have a major impact on the acute ventilatory response to hypoxia, this review suggests that the main determinant is simply the anaesthetic agent used. The review also highlights important gaps in the research literature, which may direct future research in this field. In particular, it would seem important to investigate the influence of arousal when different anaesthetic agents are used.