Guidelines for the safe practice of total intravenous anaesthesia (TIVA): Joint Guidelines from the Association of Anaesthetists and the Society for Intravenous Anaesthesia.

Guidelines are presented for safe practice in the use of intravenous drug infusions for general anaesthesia. When maintenance of general anaesthesia is by intravenous infusion, this is referred to as total intravenous anaesthesia. Although total intravenous anaesthesia has advantages for some patients, the commonest technique used for maintenance of anaesthesia in the UK and Ireland remains the administration of an inhaled volatile anaesthetic. However, the use of an inhalational technique is sometimes not possible, and in some situations, inhalational anaesthesia is contraindicated. Therefore, all anaesthetists should be able to deliver total intravenous anaesthesia competently and safely. For the purposes of simplicity, these guidelines will use the term total intravenous anaesthesia but also encompass techniques involving a combination of intravenous infusion and inhalational anaesthesia. This document is intended as a guideline for safe practice when total intravenous anaesthesia is being used, and not as a review of the pros and cons of total intravenous anaesthesia vs. inhalational anaesthesia in situations where both techniques are possible.

Finding a benchmark for monitoring hospital cleanliness.

This study evaluated three methods for monitoring hospital cleanliness. The aim was to find a benchmark that could indicate risk to patients from a contaminated environment. We performed visual monitoring, ATP bioluminescence and microbiological screening of five clinical surfaces before and after detergent-based cleaning on two wards over a four-week period. Five additional sites that were not featured in the routine domestic specification were also sampled. Measurements from all three methods were integrated and compared in order to choose appropriate levels for routine monitoring. We found that visual assessment did not reflect ATP values nor environmental contamination with microbial flora including Staphylococcus aureus and meticillin-resistant S. aureus (MRSA). There was a relationship between microbial growth categories and the proportion of ATP values exceeding a chosen benchmark but neither reliably predicted the presence of S. aureus or MRSA. ATP values were occasionally diverse. Detergent-based cleaning reduced levels of organic soil by 32% (95% confidence interval: 16-44%; P<0.001) but did not necessarily eliminate indicator staphylococci, some of which survived the cleaning process. An ATP benchmark value of 100 relative light units offered the closest correlation with microbial growth levels <2.5 cfu/cm(2) (receiver operating characteristic ROC curve sensitivity: 57%; specificity: 57%). In conclusion, microbiological and ATP monitoring confirmed environmental contamination, persistence of hospital pathogens and measured the effect on the environment from current cleaning practices. This study has provided provisional benchmarks to assist with future assessment of hospital cleanliness. Further work is required to refine practical sampling strategy and choice of benchmarks.

A review article on gastric volvulus: a challenge to diagnosis and management.

Acute gastric volvulus is a life-threatening condition, but its intermittent nature and vague symptoms may make diagnosis difficult. Imaging is usually only diagnostic if carried out when patients are symptomatic. The population affected ranges from paediatric age group to elderly with multiple co-morbidities. Laparoscopic repair is advisable once a diagnosis is reached. This review on gastric volvulus focuses on the diagnostic and management challenges encountered, together with strategies for dealing with them. Lessons have emerged which may assist in dealing with such a rare presentation in future.

Central venous catheterization and fatal cardiac tamponade.

Cardiac tamponade is a poorly recognized complication of central venous catheterization associated with a high mortality. We present a case of fatal cardiac tamponade after intra- pericardial infusion of total parenteral nutrition in a patient who had two central venous catheters. We suggest that catheter tip position should always be confirmed before use of a catheter. Tamponade should be suspected in a patient who deteriorates when a central venous catheter is used and resuscitation via the catheter should be avoided.

Drosophila dumpy is a gigantic extracellular protein required to maintain tension at epidermal-cuticle attachment sites.

BACKGROUND: Growth and morphogenesis during development depend both on patterning genes, which assign positional information, and on genes that regulate mechanical forces. The dumpy gene of the fruit fly Drosophila melanogaster is an example of the latter class, with mutant phenotypes affecting size and shape of the limbs, thoracic cuticle, trachea and mouthparts. RESULTS: The genetically complex dumpy locus was found to span over 100 kb and encode a gigantic 2.5 MDa extracellular matrix protein. Dumpy represents an extreme form of modular protein evolution, containing 308 epidermal growth factor (EGF) modules, interspersed with a new module class, DPY, and terminating in a crosslinking zona pellucida domain and membrane anchor sequence. We determined the three-dimensional structure of the DPY module by nuclear magnetic resonance (NMR) spectroscopy and found that it forms a disulphide-stabilised beta sheet motif, capable of linking end-to-end with EGF modules to form a fibre. Consistent with its cuticle phenotypes, dumpy is expressed at several sites of cuticle-epidermal cell attachment, including the trachea and the muscle tendon cells, which mediate anchorage of the muscles to the cuticle. CONCLUSIONS: The dumpy gene encodes a gigantic extracellular molecule that we predict to be a membrane-anchored fibre of almost a micrometer in length. Insertion and crosslinking of this fibre within the cuticle may provide a strong anchor for the underlying tissue, allowing it to maintain mechanical tension at sites under stress. This would explain its contribution to tissue morphogenesis through its regulation of mechanical properties.

Structural studies of synthetic peptides dissected from the voltage-gated sodium channel.

Peptides representing transmembrane regions of the alpha-subunit of the voltage-gated sodium channel were synthesised and their structures analysed, using 1H NMR and CD, in trifluoroethanol and in dodecylphosphocholine micelles. Sequence analysis suggests that the channel has six regions, S1 to S6, predicted to span the membrane in four homologous domains, designated, I, II, III and IV. Presented here are studies of representatives examples of possible single spanning segments (IS2, IS4, IVS4) and a double spanning segment, IS34, composed of segments IS3 and IS4. In addition, we investigated ISlink56, the putative linker region between segments IS5 and IS6. All of the peptides were found to have predominantly alpha-helical structures in both solvent systems. There was some evidence for bending of the longer helices but there was no discernible evidence for well-defined tertiary structure.

Use of phthaloyl protecting group for the automated synthesis of 3'-[(hydroxypropyl)amino] and 3'-[(hydroxypropyl)triglycyl] oligonucleotide conjugates.

The chemical stability of oligonucleotides (ODNs) containing 3'-propanolamine was investigated. Invariably, all the ODNs synthesized from Fmoc-protected 3-aminopropane-1,2-diol-CPG support gave a mixture of three compounds at the end of automated synthesis as analyzed by denaturing PAGE and HPLC. On the basis of analytical procedures, these compounds were identified to be 3'-[N-acetyl-N-(hydroxypropyl)amino],3'-[(hydroxypropyl)amino], and 3'-hydroxyl ODNs. The instability of the amino protecting group under the synthesis conditions was responsible for this observed heterogeneity. In order to evaluate the stability, a comparative study on the chemical stability of the ODN containing amino-protecting groups such as [(9-fluorenylmethyl)oxy]carbonyl (Fmoc), trifluoroacetyl (TFA), and phthaloyl was undertaken. The results indicate that the phthaloyl group provided the best stability for the synthesis of 3' amine-modified ODNs, and the protecting group is cleaved and deprotected in concentrated ammonium hydroxide:40% aqueous methylamine, 1:1, for 5-10 min, at 56 degrees C. The 3'-hydroxypropyl)triglycyl] ODN conjugates were also synthesized from Fmoc- and phthaloyl-protected (hydroxypropyl)triglycine-CPG supports.

An evaluation of P0.1 measured in mouth and oesophagus, during carbon dioxide rebreathing in COPD.

The pressure generated 100 ms after the onset of an occluded inspiratory effort (P0.1) is advocated and used as a measure of respiratory centre drive. We have re-examined P0.1, measured simultaneously in the mouth (Pmo0.1) and the oesophagus (Poes0.1), during carbon dioxide rebreathing, in eight patients with severe chronic obstructive pulmonary disease, to see whether either indicates central respiratory drive. Pmo0.1 was identical to Poes0.1 in 4 out of 61, greater than Poes0.1 in 18 out of 61, and less than Poes0.1 in 39 out of 61 measurements (overall Poes0.1-Pmo0.1, median +0.075, range -0.175 to +1.01 kPa). Within a rebreathing run in an individual patient, there was considerable variability in the relationship Pmo0.1/Poes0.1 (0.89 +/- 0.24), coefficient of variation (CoV%) 14.4 +/- 3.7%), in the end-expiratory oesophageal pressure (0.7 +/- 0.54 kPa, CoV% 105 +/- 106%), and in the time delay between the onset of a fall in oesophageal pressure (Poes) from the end-expiratory level to the beginning of inspiration, defined as starting when mouth pressure (Pmo) fell below atmospheric pressure (129 +/- 25 ms, CoV% 22.5 +/- 5.3%). We conclude that the problem of determining the true onset of inspiratory muscle activity from pressure data, and the likelihood that breaths are taken from different lung volumes, make it unlikely that Poes0.1 accurately represents central respiratory drive during rebreathing in chronic obstructive pulmonary disease. Furthermore, Pmo0.1 differed from Poes0.1 during rebreathing, and their relationship was not constant, so that Pmo0.1 is even less likely to be a useful reflection of central nervous system output or respiratory centre drive in such patients.

Diaphragmatic dysfunction in neuralgic amyotrophy: an electrophysiologic evaluation of 16 patients presenting with dyspnea.

We report 16 adult men (age, 41 to 75 yr) with neuralgic amyotrophy (NA) who presented with dyspnea due to involvement of the diaphragm. All patients developed breathlessness after a prodrome of acute severe neck and shoulder pain. Bilateral diaphragm paralysis (BDP) was confirmed in 12 patients and unilateral diaphragm paralysis (UDP) in four by the absence of electrical and mechanical responses to percutaneous phrenic nerve stimulation. Global expiratory muscle strength was well preserved in all patients, but inspiratory muscle strength was reduced in proportion to the extent of diaphragmatic involvement. Lung function showed low lung volumes with preservation of carbon monoxide transfer coefficient in all patients. Two BDP patients were hypoxic (PaO2 = 67 and 54 mm Hg, respectively) on daytime arterial blood gas analysis; the latter patient with pre-existing chronic obstructive pulmonary disease and marked obesity also had borderline hypercapnia (PaO2 = 49 mm Hg). Overnight sleep studies in three BDP and two UDP patients showed frequent intermittent arterial oxygen desaturations apparently caused by obstructive sleep apneas, but there was no evidence of alveolar hypoventilation. Follow-up muscle studies in five BDP and four UDP patients between 2 and 4 yr after initial referral showed complete recovery of diaphragmatic function in only two UDP patients, one of whom relapsed a year later. We postulate that NA may be an important but underrecognized cause of diaphragmatic paralysis in otherwise normal patients. Diaphragmatic strength returns very slowly, if at all.

Inspiratory muscle effort during nasal intermittent positive pressure ventilation in patients with chronic obstructive airways disease.

Effective intermittent positive pressure ventilation can be achieved noninvasively using a nasal mask, but patient comfort may be compromised and respiratory effort increased unless the trigger threshold is low and the response time of the ventilator short. The effect of nasal ventilation upon inspiratory muscle effort and the functional characteristics of the trigger of a purpose-built ventilator were evaluated in five patients with chronic obstructive airways disease. A measure of inspiratory muscle effort, the average pressure time integral per minute, decreased by at least 80% in four patients and by 50% in one. Only two patients had significant numbers of triggered breaths (17% and 47% of total) during 1 h of ventilation with settings as used at home. Therefore trigger function was evaluated when the patients were made to trigger the ventilator by slowing the control rate. A high resting end-expiratory intrathoracic pressure decreased the effective trigger sensitivity so that a mean (SD) change in oesophageal pressure of 14.8 cmH2O was required to lower mask pressure by 2.4 (0.3) cmH2O and activate the trigger. Even under these conditions of lowest trigger sensitivity inspiratory muscle effort was not increased compared to spontaneous ventilation.

Three dimensional structure of the transmembrane region of the proto-oncogenic and oncogenic forms of the neu protein.

The neu proto-oncogene may be converted into a dominantly transforming oncogene by a single point mutation. Substitution of a valine residue at position 664 in the transmembrane region with glutamic acid activates the tyrosine kinase of the molecule and is associated with increased receptor dimerization. Previously we have proposed a model in which the glutamic acid side chain stabilizes receptor dimerization by hydrogen bonding. Other models have been proposed in which the mutation leads to a conformational change in the transmembrane region mimicking that assumed to occur following binding of a natural ligand. Synthetic peptides representing part of the transmembrane region were prepared. Some residues were replaced with serine in order to improve peptide solubility to allow purification and analysis. Both the peptides containing valine and glutamic acid dissolved in water and in an artificial lipid monolayer. The structures of the peptides were determined by NMR spectroscopy to be alpha-helical. No significant difference in conformation was observed between the two peptides. This result does not support the model proposing a conformational change. The receptor structures determined experimentally do allow alternative models involving receptor transmembrane region packing.

Maximal relaxation rate of inspiratory muscle can be effort-dependent and reflect the activation of fast-twitch fibers.

We have measured the normalized maximal relaxation rate (MRR, % pressure loss/10 ms) of esophageal and transdiaphragmatic pressures in five normal subjects who performed unoccluded shifts from FRC, with the peak pressure varying between 10 and 100% of each subject's maximum. MRR was computed as the maximal rate of decay of pressure divided by the peak pressure, with units of %pressure loss/10 ms. We observed that MRR became progressively faster as sniff peak pressure increased in amplitude above 10% maximum. In four subjects this trend was most marked for sniffs of less than 40% maximal pressure, with little change as peak pressure increased further. In a fifth subject this trend continued across the full range of pressure. Thus, MRR may be an effort-dependent variable during voluntary inspiratory maneuvers. We postulate that sniff MRR becomes faster with increasing peak pressure because of progressive activation of fast-twitch type II muscle fibers. The findings of this study suggest that erroneous conclusions about the significance of slowing of sniff MRR with fatigue may be made if MRR is determined from voluntary efforts with a peak pressure of less than 60% of control maximum, as may occur with fatigue.

Domiciliary nocturnal nasal intermittent positive pressure ventilation in COPD: mechanisms underlying changes in arterial blood gas tensions.

The improvement in arterial blood gas tensions following assisted ventilation in chronic obstructive pulmonary disease (COPD) has usually been attributed to the relief of incipient or established respiratory muscle fatigue. The contribution of changes in the load placed upon and the drive to the respiratory muscle pump have not been evaluated. We have investigated the contribution of changes in respiratory muscle strength, the ventilatory response to CO2 and ventilatory function to changes in arterial blood gas tensions in eight patients with severe COPD completing six months domiciliary nasal intermittent positive pressure ventilation. Six patients showed a reduction and two an increase in arterial carbon dioxide tension (PaCO2), median (range) for eight patients, -0.9 kPa (-1.5 to +0.4) (p less than 0.05) and seven showed an improvement in arterial oxygen tension (PaO2), +0.7 kPa (-0.4 to +1.7) (p less than 0.05) during daytime spontaneous breathing. The reduction in PaCO2 was not related to increased inspiratory muscle strength but was correlated with a decrease in gas trapping (Spearman rank correlation coefficient (r(S)) 0.85, p less than 0.05) and in the residual volume (r(s) 0.78, p less than 0.05), suggesting reduced small airway obstruction and, therefore, a reduction in load. The change in PaCO2 also correlated with the increase in ventilation at an end-tidal CO2 of 8 kPa during rebreathing (r(s) -0.76, p less than 0.05) suggesting improved chemosensitivity to CO2. Our data do not support the hypothesis that improvements were due to the relief of muscle fatigue. We suggest that the contribution of changes in load and central drive warrant further investigation.

Inspiratory muscle relaxation rate after voluntary maximal isocapnic ventilation in humans.

We have investigated whether the capacity of the inspiratory muscles to generate pressure and flow during a ventilatory load is related to changes in inspiratory muscle relaxation rate. Five highly motivated normal subjects performed voluntary maximal isocapnic ventilation (MIV) for 2 min. Minute ventilation and esophageal, gastric, and transdiaphragmatic pressures were measured breath by breath. We observed that ventilation, peak inspiratory and expiratory pressures, and inspiratory flow rate declined from the start of the run to reach a plateau at 60 s that was sustained for the remainder of the exercise. In a subsequent series of studies, MIV was performed for variable durations between 15 and 120 s. The normalized maximum relaxation rate of unoccluded inspiratory sniffs (sniff MRR, %pressure loss/10 ms) was determined immediately on stopping MIV. Sniff MRR slowed as the duration of MIV increased and paralleled the decline in inspiratory pressure and ventilation observed during the 2-min exercise. No further slowing in MRR occurred when ventilation became sustainable. We conclude that, during MIV, the progressive loss of ventilation and capacity to generate pressure is associated with the early onset and progression of a peripheral fatiguing process within the inspiratory muscles.

Phrenic nerve injury in infants and children undergoing cardiac surgery.

Fifty infants and 50 children less than 15 years undergoing palliative or corrective cardiac surgery in the Brompton Hospital between March and October 1988 had direct percutaneous stimulation of the phrenic nerve before and after operation. Ten patients, six under 1 year of age and four over, developed unilateral phrenic nerve injury. In those aged less than 1 year recovery after operation was prolonged because their diaphragmatic palsy made it difficult to wean them from the ventilator. Older children had symptoms but their rate of recovery did not seem to be affected by the phrenic nerve injury. Phrenic nerve damage was no more frequent after a lateral thoracotomy than after a median sternotomy. There was no significant association with the type of operation performed, the experience of the surgeon, the use of bypass or topical ice, the duration of bypass, circulatory arrest or aortic cross clamping, or the age of the patient at the time of operation. In patients who had cardiopulmonary bypass the risk of injury was significantly higher in those who had undergone previous operation. The 10% frequency of phrenic nerve injury determined in this prospective study was higher than that seen in earlier retrospective reports. Direct percutaneous stimulation of the phrenic nerve can be used at the bedside in infants and children to facilitate early and accurate diagnosis of phrenic nerve palsy, and the results may influence early management.

Sniff esophageal and nasopharyngeal pressures and maximal relaxation rates in patients with respiratory dysfunction.

Sniff esophageal pressure (Pes) and maximal relaxation rate (MRR, percent pressure loss/10 ms) are useful measurements of inspiratory muscle performance, but they require the passage of an esophageal balloon. We have examined the relationship between sniff esophageal and nasopharyngeal pressures (sniff Pes, sniff Pnp) and maximal relaxation rates (Pes MRR, Pnp MRR) in 13 patients with chronic obstructive pulmonary disease (COPD), five with intrapulmonary fibrosis (IPF), and seven with the "shrinking lung syndrome" of systemic lupus erythematosus (SLE). The ratio sniff Pnp/Pes (mean +/- SD) was 0.65 +/- 0.15 in COPD, 0.76 +/- 0.18 in IPF, and 0.91 +/- 0.03 in SLE. The ratio Pnp/Pes MRR was 1.20 +/- 0.2 in COPD, 1.14 +/- 0.12 in IPF, and 1.07 +/- 0.13 in SLE. We confirm that the transmission of pleural pressure to the upper airways during brief dynamic maneuvers is impaired in the presence of airway obstruction and lung fibrosis. We conclude that measurements of sniff Pnp and Pnp MRR are of limited value in patients with abnormal lung mechanics.