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Biomedical subjects

J A Langton

Publications and source records attributed to J A Langton.

At least 19 recordsLinked to original sources

An investigation into the effects of midazolam and propofol on human respiratory cilia beat frequency in vitro.

OBJECTIVE: Patients in intensive care are known to be prone to both upper and lower respiratory tract infection. Respiratory mucus forms a barrier to infection. Mucus transport rate (MTR) depends upon both the physical properties of mucus and the action of respiratory cilia. Patients undergoing anaesthesia are known to have a reduced MTR that may be related to a depressant effect on cilia beat frequency (CBF) by anaesthetic drugs. The aim of this study was to investigate the effects of two commonly used intensive care sedative agents, midazolam and propofol, on CBF using human nasal turbinate explants in vitro. DESIGN: We exposed ciliated tissue from human nasal turbinate explants to midazolam and propofol in supraclinical concentrations (20 microM midazolam and 70 microM propofol) in a controlled and blinded manner for 90 min and measured CBF by the transmitted light technique. RESULTS: After 90 min, mean (SEM) CBF in the group exposed to midazolam and its control group were 13.0 (0.2) Hz and 12.9 (0.3) Hz, respectively. Mean (SEM) CBF in the group exposed to propofol was 13.6 (0.4) Hz and in the control group the value was 12.0 (0.6) Hz. There was no significant change in CBF (midazolam: p = 0.21, propofol: p = 0.31, MANOVA for repeated measures). CONCLUSIONS: We have found no effect of midazolam or propofol in supra-clinical concentrations upon CBF in human turbinate explants after a 90-min exposure. This contrasts with previous work that has shown a depressant effect of inhalational anaesthetic agents on CBF.

Cilia

Recovery characteristics using single-breath 8% sevoflurane or propofol for induction of anaesthesia in day-case arthroscopy patients.

We studied the induction and recovery characteristics following inhalational induction with 8% sevoflurane in nitrous oxide and oxygen compared with intravenous propofol in 40 patients presenting for arthroscopy of the knee. Patients were randomly allocated to receive either induction agent, and anaesthesia was then maintained with sevoflurane in oxygen and nitrous oxide. A computerised test of hand--eye co-ordination and a p-deletion test were used to measure psychomotor recovery. The sevoflurane group had a faster onset of anaesthesia time. No significant differences between the groups were found in time to eye opening or psychomotor tests. Nausea and vomiting scores were significantly higher at 30 min in the sevoflurane group (p = 0.04); this difference was no longer significant by 90 min. We conclude that inhalational induction with sevoflurane in these patients has no important clinical advantages and causes more nausea and vomiting than propofol.

Adolescent

Effect of an upper respiratory tract infection on upper airway reactivity.

Patients presenting for elective anaesthesia and surgery may be suffering with, or recovering from, a recent upper respiratory tract infection (URTI). It is a frequent clinical problem as to whether to postpone surgery in such patients as they may be more likely to suffer adverse respiratory events related to administration of general anaesthesia. Using dilute ammonia vapour as a chemical stimulus, we measured upper airway reactivity in 11 healthy volunteers (six males), mean age 39.8 (range 30-58) yr, who had symptoms of an URTI. Volunteers were recruited 24-72 h after symptoms first began, and followed-up at regular intervals for the next 8 weeks. Measurements of upper airway reactivity were made on the following days (+/- 24h) after commencement of URTI symptoms: 3, 6, 9, 15, 20 and 27. Additional measurements were obtained 56 days after symptoms first began, and these were regarded as baseline measurements. Upper airway reactivity was increased on days 3, 6 and 9 compared with baseline measurements (P < 0.01, Wilcoxon). There was no significant change in airway reactivity from day 15 onwards, by which time 10 of the 11 subjects were completely devoid of symptoms. All subjects were asymptomatic by day 20 and remained so until the study ended on day 56. We conclude that upper airway reactivity was increased during the acute phase of an URTI, and that this appeared to be related to the presence of symptoms.

Acute Disease

Effect of nebulised lignocaine on the quality of induction of anaesthesia in cigarette smokers.

We have assessed the effect of nebulised lignocaine, given pre-operatively, upon the quality of induction of anaesthesia in cigarette smokers. Seventy-five patients were studied in a double-blind randomised fashion, receiving a nebuliser of either 4 ml 0.9% NaCl or 4 ml 4% lignocaine. All patients received a standardised anaesthetic consisting of thiopentone followed by progressive increments of enflurane. Thirty-three out of 38 patients (87%) who received nebulised lignocaine had induction without adverse events, compared with 25 out of 37 patients (68%) in the nebulised saline group (Chi-squared test p < 0.05). We conclude that the use of nebulised lignocaine, administered pre-operatively, improves the quality of induction of anaesthesia in cigarette smokers.

Administration, Inhalation

The site of airway irritation during induction of anaesthesia.

The aim of this investigation was to study the role of the nasal airway in mediating upper airway reflexes during induction of anaesthesia when the commonly used irritant inhalational anaesthetic agent enflurane is used. In a prospective randomised study, 40 ASA 1 & 2 day-case patients undergoing body surface surgery were recruited. Following intravenous induction using propofol, 20 patients received enflurane administered via a laryngeal mask airway (LMA), the anaesthetic vapour therefore bypassing the nasal airway. In the other group, 20 patients received enflurane anaesthesia administered using a face mask, the nasal airway therefore being exposed to inhalation anaesthetic. We were unable to demonstrate any significant (p < 0.05) differences between the two groups in relation to upper airway complications (cough, breath holding, laryngeal spasm, bronchospasm and excitement). Previous work has identified the nose as a possible important reflexogenic site for upper airway reflexes in humans during anaesthesia. We have been unable to demonstrate any difference in upper airway complications when the nasal airway was included or excluded from exposure to irritant anaesthetic vapours, when administered in a clinical setting.

Adolescent

A perfusion system for in vitro measurement of human cilia beat frequency.

We have designed and built a perfusion system and perfusion chamber to allow investigation of the effects of anaesthetic agents on human cilia in vitro. Using this system, samples of human respiratory cilia can be maintained in a stable and controlled environment for several hours. We measured cilia beat frequency of nasal respiratory epithelium from 10 healthy volunteers; cilia beat frequency was constant over a 4-h period, and measurements were found to be in good agreement with previously published work [1]. In a separate study we investigated the effect of a sleep dose of propofol on cilia beat frequency in samples from six patients undergoing minor surgery; samples were obtained before and immediately after induction of anaesthesia with propofol 2-3 mg kg-1. There was no statistically significant difference in cilia beat frequency between data obtained before and after induction with propofol.

Adult

Effects of 3 MAC of halothane, enflurane and isoflurane on cilia beat frequency of human nasal epithelium in vitro.

We have measured the effects of three times the minimum alveolar concentration (MAC) of halothane, enflurane and isoflurane on cilia beat frequency of human nasal epithelial brushings from 18 healthy adult patients. Using the transmitted light technique and paired perfusion chambers, the cilia were exposed to 2.25% halothane, 5% enflurane or 3.6% isoflurane in air, or air alone, in a controlled and blinded manner. Over a 4-h observation period, cilia beat frequency of the samples exposed to inhalation anaesthetic agents demonstrated a significant reduction in frequency compared with controls exposed to air alone. Mean cilia beat frequency for the samples exposed to halothane was 9.3 (SEM 1.3) compared with its controls of 11.4 (1.0); for the samples exposed to enflurane, 10.9 (1.3) compared with its controls of 11.6 (1.2); and for the samples exposed to isoflurane, 10.8 (1.1) compared with its controls of 11.6 (1.2). There was a statistically significant difference between the samples exposed to all three volatile agents and their associated controls (halothane, P = 0.01; enflurane, P = 0.03; isoflurane, P = 0.01; nested repeated measures analysis of variance utilizing polynomial contrasts).

Adult

Effects of morphine on human nasal cilia beat frequency in vitro.

Using human nasal cytological brushings, we have investigated the effects of morphine on ciliary function by measurement of cilia beat frequency in vitro, and we have also determined opioid receptor binding in these specimens. We obtained ciliated samples from seven volunteers, and measured cilia beat frequency using the transmitted light technique during exposure to morphine 10 mumol litre-1 for 4 h. Mean cilia beat frequency of the samples exposed to morphine was 11.1 (95% confidence interval 10.9-11.5) Hz and that of the controls 11.3 (11.1-11.7) Hz. There was no significant effect of morphine on human cilia beat frequency in vitro (MANOVA for repeated measures and nested, F = 0.61, P = 0.66). In a separate study, we obtained nasal brushings from 20 patients and measured the binding of the opioid antagonist tritiated diprenorphine ([3H]DPN). Mean disintegrations per minute (dpm) for total and non-specific binding were 9036 (8105-9967) dpm and 9130 (8054-10206) dpm, respectively. These values did not differ significantly (paired t test, t = 0.22, P = 0.83). We conclude that morphine had no effect on cilia beat frequency in vitro and we were unable to demonstrate any significant numbers of opioid receptors on nasal ciliated epithelium.

Adult

Recovery of respiratory ciliary function after depression by inhalation anaesthetic agents: an in vitro study using nasal turbinate explants.

We have developed a human tissue preparation suitable for measurement of cilia beat frequency derived from nasal turbinates. Cilia beat frequency of turbinate explants from 11 patients did not change significantly over a 10-day observation period while maintained in an incubator, with mean cilia beat frequency of 13.1 (SEM 0.3) Hz to 14.4 (0.2) Hz (ANOVA for repeated measures, P = 0.168). We have used this preparation to investigate recovery of ciliary function after depression by inhalation anaesthetic agents. Eight or nine turbinate explants were exposed to three times the minimum alveolar concentration (MAC) of halothane, enflurane or isoflurane for a period of 1 h and thereafter to a period of air washout. After exposure to the inhalation agent there was a significant reduction in cilia beat frequency with all three agents: halothane 14.3 (0.4) Hz to 9.5 (0.3) Hz; enflurane 13.7 (0.6) Hz to 10.5 (0.5) Hz;isoflurane 15.9 (0.6) Hz to 10.6 (0.3) Hz. Cilia beat frequency returned to values after air washout that were not significantly different from baseline after 90 min of washout of halothane and 60 min of washout of enflurane and isoflurane (repeated measures ANOVA, unpaired t test; P = 0.01 at 60 min and P = 0.31 at 90 min washout for halothane; P = 0.83 at 60 min washout for enflurane; P = 0.26 at 60 min washout for isoflurane).

Adult

Effects of topical benzocaine and lignocaine on upper airway reflex sensitivity.

We studied the degree and duration of effect on upper airway reflex sensitivity of oral benzocaine lozenges, nebulised lignocaine and lignocaine sprayed onto the vocal cords under direct vision, using low concentrations of ammonia as a stimulus to upper airway receptors. Ten minutes after the administration of oral benzocaine 20 mg the threshold response of the upper airway to ammonia (NH3TR) had risen significantly from baseline mean (SEM) of 680 (95) to 975 (109) ppm of ammonia with a return to baseline values after 25 min (n = 8, p < 0.05, repeated measures of ANOVA; p < 0.001, t-test). A direct spray of lignocaine 100 mg onto the vocal cords resulted in a significant elevation in NH3TR from a baseline mean (SEM) of 665 (81) to a maximum of 1600 (88) ppm of ammonia with a significant elevation in the threshold persisting for 100 min (n = 7, p < 0.001, repeated measures of ANOVA; p < 0.05, t-test). The application of 4% nebulised lignocaine 4 ml significantly increased NH3TR from a baseline mean (SEM) of 770 (56) to a maximum of 1190 (63) ppm of ammonia with a significant elevation in the threshold persisting for 30 min (n = 8, p < 0.001, repeated measures of ANOVA; p < 0.05, t-test). The maximum elevations in NH3TR with the two methods of lignocaine delivery were significantly different (p < 0.01, 2-way ANOVA).

Administration, Oral

Postoperative laryngeal competence. The laryngeal mask airway and tracheal tube compared.

We investigated the incidence of postoperative laryngeal incompetence in 40 patients undergoing lower limb arthroplasty. Patients were randomly allocated to one of two groups using a standardised general anaesthetic/muscle relaxant technique; in group A the patients' lungs were ventilated via a laryngeal mask airway and in group B via a tracheal tube. Following recovery from general anaesthesia, at a time when patients were considered safe for discharge back to the general ward, they were asked to swallow 20 ml of barium, and an immediate portable chest X ray was taken. The X rays were examined for evidence of tracheopulmonary aspiration. Contrary to previous studies the incidence of aspiration was low, occurring in only one patient. This aspiration was, however, clinically silent. The exact mechanism of this apparent laryngeal incompetence, which occurred in a patient from the tracheal tube group, is unclear. Due to the relatively small numbers of patients studied no conclusions can be drawn about the relative benefits of the use of the laryngeal mask airway with regard to postoperative laryngeal competence.

Aged

The output of an 'empty' Tec 3 vaporizer.

The output of 30 Tec 3 vaporizers (halothane, enflurane and isoflurane) was studied, starting at the point where no liquid was visible in the content window. At 6 l.min-1 and 1% v/v initial output, consistent delivery was on average maintained for in excess of 90 (range 55-120) min. Thereafter, output declined rapidly. At the flows and concentrations studied there is a significant reserve in the vaporizing chamber, but it is likely that when higher flows and concentrations are used this reserve may be substantially reduced.

Anesthesia, Inhalation

Sensitivity of upper airway reflexes in cigarette smokers: effect of abstinence.

In two studies we have compared the upper airway reflex sensitivity (UARS) of chronic cigarette smokers with that of non-smokers and also the effect of different periods of abstinence on UARS in the smoking groups. UARS was measured by recording the threshold concentration of dilute ammonia vapour required to stimulate reflex glottic closure. The first study compared UARS in 20 non-smokers with 20 smokers, followed by another measurement in the smoking group after 24 h of abstinence. In study two, we measured UARS repeatedly over a period of 3-4 weeks in 16 smokers, half of whom had stopped smoking on day 0. Chronic cigarette smokers were found to have significantly greater UARS compared with non-smokers; the sensitivity was unaltered after 24 h of abstinence but was found to reduce over several days, the change commencing between 24 and 48 h, with most achieving a consistent change within 10 days.

Adolescent

Effect of halothane on cilia beat frequency of ciliated human respiratory epithelium in vitro.

The effect of halothane on human ciliated nasal epithelium was studied in vitro. Samples from 24 healthy adult volunteers were exposed to halothane in varying concentrations and cilia beat frequency was measured using the transmitted light technique. Mean cilia beat frequency was measured at 30-min intervals. There was a significant decrease in cilia beat frequency at 2 h in samples that were exposed to halothane (mean 8.4 (SD 2.5) Hz, 9.18 (2.6) Hz and 6.99 (4.9) Hz) compared with air (10.8 (2.7) Hz, 11.6 (2.1) Hz and 12.1 (2.3) Hz) (P < 0.01). The coefficient of variation of cilia beat frequency measurements increased after exposure to halothane. There was no change in the cilia beat frequency of controls exposed to air over a 3-h period.

Adult

The effect of intravenously administered diazepam, midazolam and flumazenil on the sensitivity of upper airway reflexes.

This investigation studied the effect of two intravenous benzodiazepines and the specific reversal agent, flumazenil, on the sensitivity of upper airway reflexes. In a blinded, randomised, crossover study, we have investigated the effect of a single dose of diazepam ('Diazemuls') (0.2 mg.kg-1) and midazolam (0.07 mg.kg-1), both given intravenously on the sensitivity of upper airway reflexes in eight male volunteers. Reflex sensitivity was assessed by identification of reflex glottic closure in response to a threshold concentration of inhaled ammonia vapour. Both diazepam and midazolam produced significant depression of upper airway reflex sensitivity. This was maximum with both drugs within 10 min of administration, but baseline sensitivity was regained within 60 min. Flumazenil (300 micrograms) administered 10 min after midazolam, resulted in significant reversal of the upper airway reflex sensitivity depression.

Adult

The effect of halothane on neonatal ciliary beat frequency.

The effect of a commonly used anaesthetic agent, halothane, on neonatal cilial function was determined. A nasal cilial sample was taken from 13 healthy, term, newborn infants. For 1 h, half of each sample was exposed to halothane and half to air. Cilial function was assessed by measuring beat frequency with a modified light transmission method. Cilial beat frequency was significantly slower in the cilia exposed to halothane, 9(s.d. 2.5)Hz, than to air, 12.9(s.d. 1.5)Hz. Decreased mucociliary clearance following halothane anaesthesia is due, at least in part, to a directly depressant effect of halothane on ciliated cells.

Air