Haemodynamic changes to a midazolam-fentanyl-rocuronium protocol for pre-hospital anaesthesia following return of spontaneous circulation after cardiac arrest.

Following the return of spontaneous circulation after out-of-hospital cardiac arrest, neurological dysfunction, airway or ventilatory compromise can impede transport to early percutaneous coronary intervention, necessitating pre-hospital or emergency department anaesthesia to facilitate this procedure. There are no published reports of the ideal induction agents in these patients. We sought to describe haemodynamic changes associated with induction of anaesthesia using a midazolam (0.1 mg.kg-1 ), fentanyl (2 µg.kg-1 ) and rocuronium (1 mg.kg-1 ) regimen developed using expert opinion, and adherence to the protocol by our pre-hospital teams. We performed a retrospective review of haemodynamic data recorded during induction of anaesthesia in patients following return of spontaneous circulation, over a 30-month period. We analysed the changes in systolic blood pressure and heart rate using a repeated-measures design, as well as the rate of new hypotension or hypertension. Sixty-four patients had four consecutive measurements for analysis (one pre-induction and three post-induction). Systolic blood pressure at all three post-induction measurements was significantly lower than the pre-induction value. Heart rate did not differ between any time-points. New episodes of hypotension (systolic pressure < 90 mmHg) occurred in four (6%) patients at the first measurement post-induction (95%CI 2-15%) and 10 (16%) at the third measurement (95%CI 8-27%). Three patients (5%; 95%CI 1-13%) had a hypertensive response. The median (IQR[range]) dose of midazolam given at induction was 0.04 (0.03-0.05 [0.01 to 0.10]) mg.kg-1 . Adherence to recommended fentanyl and rocuronium doses was high. Overall, systolic blood pressure was reduced following induction of anaesthesia, and systolic pressures < 90 mmHg occurred more often at measurements made later (up to 9 min) after induction. Changes in heart rate, and new hypertension were uncommon.

A prospective, randomised trial of pre-oxygenation strategies available in the pre-hospital environment.

Pre-oxygenation before tracheal intubation aims to increase safe apnoea duration by denitrogenation of the functional residual capacity of the lungs, and increasing oxygen stores at the onset of apnoea. Pre-oxygenation options in the pre-hospital environment are limited due to oxygen availability and equipment portability. The aim of this study was to evaluate the effectiveness of strategies available in this setting. This was a prospective, randomised, crossover study of 30 healthy volunteers who underwent 3-min periods of pre-oxygenation by tidal volume breathing with a non-rebreather mask, a bag-valve-mask and a portable ventilator. The primary outcome measure was fractional expired oxygen concentration of the first exhaled breath after each technique. The secondary outcome measure was ease of breathing, assessed using a visual analogue scale. The mean (95%CI) fractional expired oxygen concentrations achieved with the non-rebreather mask were 64 (60-68)%, bag-valve-mask 89 (86-92)% and portable ventilator 95 (94-96)%. Pre-oxygenation efficacy with the non-rebreather mask was significantly worse than with either the bag-valve-mask (p < 0.001) or ventilator (p < 0.001). No significant difference in ease of breathing was identified between the bag-valve-mask and ventilator, but both were perceived as being significantly more difficult to breathe through than the non-rebreather mask. We conclude that, in healthy volunteers, the effectiveness of pre-oxygenation by bag-valve-mask and portable ventilator was superior to pre-oxygenation with a non-rebreather mask, although the non-rebreather mask was easier to breathe through than the other pre-oxygenation devices.

The injury patterns, management and outcomes of retroperitoneal haemorrhage caused by lumbar arterial bleeding at a Level-1 Trauma Centre: A 10-year retrospective review.

PURPOSE: Haemorrhagic shock remains a leading preventable cause of death amongst trauma patients. Failure to identify retroperitoneal haemorrhage (RPH) can lead to irreversible haemorrhagic shock. The arteries of the middle retroperitoneal region (i.e., the 1st to 4th lumbar arteries) are complicit in haemorrhage into the retroperitoneal space. However, predictive injury patterns and subsequent management implications of haemorrhage secondary to bleeding of these arteries is lacking. MATERIALS AND METHODS: We performed a retrospective cohort study of patients diagnosed with retroperitoneal haemorrhage who presented to our Level-1 Trauma Centre (2009-2019). We described the associated injuries, management and outcomes relating to haemorrhage of lumbar arteries (L1-4) from this cohort to assess risk and management priorities in non-cavitary haemorrhage compared to RPH due to other causes. RESULTS: Haemorrhage of the lumbar arteries (LA) is associated with a higher proportion of lumbar transverse process (TP) fractures. Bleeding from branches of these vessels is associated with lower systolic blood pressure, increased incidence of massive transfusion, higher shock index, and a higher Injury Severity Score (ISS). A higher proportion of patients in the LA group underwent angioembolisation when compared to other causes of RPH. CONCLUSION: This study highlights the injury patterns, particularly TP fractures, in the prediction, early detection and management of haemorrhage from the lumbar arteries (L1-4). Compared to other causes of RPH, bleeding of the LA responds to early, aggressive haemorrhage control through angioembolisation. These injuries are likely best treated in Level-1 or Level-2 trauma facilities that are equipped with angioembolisation facilities or hybrid theatres to facilitate early identification and management of thoracolumbar bleeds.

Can a familial gastrointestinal tumour syndrome be allelic with Waardenburg syndrome?

Familial gastrointestinal stromal tumours (GISTs) are rare but otherwise well-characterized tumour syndromes, most commonly occurring on a background of germline-activating mutations in the tyrosine kinase receptor c-KIT. The associated clinical spectrum reflects the constitutive activation of this gene product across a number of cell lines, generating gain-of-function phenotypes in interstitial cells of Cajal (GIST and dysphagia), mast cells (mastocytosis) and melanocytes (hyperpigmentation). We report a three-generation kindred harbouring a c-KIT germline-activating mutation resulting in multifocal GISTs, dysphagia and a complex melanocyte hyperpigmentation and hypopigmentation disorder, the latter with features typical of those observed in Waardenburg type 2 syndrome (WS2F). Sequencing of genes known to be causative for WS [microphthalmia transcription factor (MITF), Pax3, Sox10, SNAI2 ] failed to show any candidate mutations to explain this complex cutaneous depigmentation phenotype. Our case report conclusively expands the clinical spectrum of familial GISTs and shows a hitherto unrecognized link to WS. Possible mechanisms responsible for this novel cause of WS2F will be discussed.

Differential involvement of glutamatergic mechanisms in the cognitive and subjective effects of smoking.

There is growing preclinical evidence for the involvement of glutamate in the behavioral actions of nicotine. The aim of this study, was to investigate the role of N-methyl-D-aspartate (NMDA) receptors in the cognitive and subjective effects of smoking in humans. Sixty regular smokers took part in this double-blind placebo controlled study, that investigated the effect of the NMDA-antagonist memantine (40 mg) and the nicotinic-receptor antagonist mecamylamine (10 mg) on smoking-induced improvement in performance of a task of sustained attention and on smoking-induced changes in subjective effects and craving. Increases in subjective ratings of 'buzzed' following smoking were reversed by memantine, but not by mecamylamine. In contrast, improvement on a Rapid Visual Information Processing task by smoking was opposed by mecamylamine, but not by memantine. Smoking reduced craving for cigarettes, but neither drug altered this effect. Our results suggest that glutamatergic mechanisms may have differential involvement in the subjective and cognitive actions of smoking. Further investigations using different ligands are warranted to fully characterize the role of glutamate underlying the consequences of smoking behavior.

NMR studies of melanins: characterization of a soluble melanin free acid from Sepia ink.

This paper deals with the nuclear magnetic resonance characterization of a soluble derivative (melanin free acid) of Sepia melanin obtained by a peroxidative treatment of the parent (insoluble) species. High resolution 13C and 15N solid state NMR spectroscopies allow the assessment of the chemical changes occurring in the macromolecule upon solubilization. 1H and 13C NMR solution spectra are discussed in light of the results obtained from the solid state spectra. Furthermore, the coordination properties of melanin have been investigated through 27Al NMR spectroscopy and proton relaxation enhancement studies of the paramagnetic gadolinium complex of melanin free acid. Through these experiments it has been possible to evaluate the molecular reorientational time tau R (and from it an estimated molecular weight close to 20 KDa) and the strength of the metal-macromolecule interaction.