The effect of restrictive compared to liberal intravenous fluid volume on hypotension in adults undergoing major abdominal surgery.

In a cardiac output (CO) sub-study of the Restrictive versus Liberal Fluid Therapy in Major Abdominal Surgery (RELIEF) trial, it was shown that restrictive fluid management was associated with lower cardiac index at the end of surgery. However, the association of the fluid protocol with intraoperative blood pressure was less clear. This paper primarily compares rates of hypotension between the two fluid regimens. The haemodynamic effects of these protocols may increase our understanding of perioperative fluid prescription. Using a data set of arterial pressure and cardiac output measurements, this observational cohort study primarily compares intraoperative hypotension rates defined by a mean arterial pressure < 65 mmHg between liberal and restrictive fluid protocols. Secondary analyses explore predictors of invasive mean arterial pressure and doppler-derived cardiac output, including fluid volume regimens and surgical duration. 105 patients had a combined total of 835 haemodynamic data capture events from the beginning to the end of the surgery. Here we report that a restrictive regimen is not associated with a greater proportion of participants who experience at least one episode of hypotension than the liberal regimen 64.1% vs. 61.5% (mean difference 2.6%, 95% CI - 15.9% to 21%, p = 0.78). Duration of surgery was associated with an increased risk of hypotension (OR 1.05, 1 to 1.1, p = 0.038). A fluid restriction protocol compared to liberal fluid administration is not associated with lower blood pressure.

Effect of fluid strategy on stroke volume, cardiac output, and fluid responsiveness in adult patients undergoing major abdominal surgery: a sub-study of the Restrictive versus Liberal Fluid Therapy in Major Abdominal Surgery (RELIEF) trial.

BACKGROUND: We designed a prospective sub-study of the larger Restrictive versus Liberal Fluid Therapy in Major Abdominal Surgery (RELIEF) trial to measure differences in stroke volume and other haemodynamic parameters at the end of the intraoperative fluid protocols. The haemodynamic effects of the two fluid regimens may increase our understanding of the observed perioperative outcomes. METHODS: Stroke volume and cardiac output were measured with both an oesophageal Doppler ultrasound monitor and arterial pressure waveform analysis. Stroke volume variation, pulse pressure variation, and plethysmographic variability index were also obtained. A passive leg raise manoeuvre was performed to identify fluid responsiveness. RESULTS: Analysis of 105 patients showed that the primary outcome, Doppler monitor-derived stroke volume index, was higher in the liberal group: restrictive 38.5 (28.6-48.8) vs liberal 44.0 (34.9-61.9) ml m-2; P=0.043. Similarly, there was a higher cardiac index in the liberal group: 2.96 (2.32-4.05) vs 2.42 (1.94-3.26) L min-1 m-2; P=0.015. Arterial-pressure-based stroke volume and cardiac index did not differ, nor was there a significant difference in stroke volume variation, pulse pressure variation, or plethysmographic variability index. The passive leg raise manoeuvre showed fluid responsiveness in 40% of restrictive and 30% of liberal protocol patients (not significant). CONCLUSIONS: The liberal fluid group from the RELIEF trial had significantly higher Doppler ultrasound monitor-derived stroke volume and cardiac output compared with the restrictive fluid group at the end of the intraoperative period. Measures of fluid responsiveness did not differ significantly between groups. CLINICAL TRIAL REGISTRATION: ACTRN12615000125527.

Aerosolisation in endonasal endoscopic pituitary surgery.

PURPOSE: To determine the particle size, concentration, airborne duration and spread during endoscopic endonasal pituitary surgery in actual patients in a theatre setting. METHODS: This observational study recruited a convenience sample of three patients. Procedures were performed in a positive pressure operating room. Particle image velocimetry and spectrometry with air sampling were used for aerosol detection. RESULTS: Intubation and extubation generated small particles (< 5 µm) in mean concentrations 12 times greater than background noise (p < 0.001). The mean particle concentrations during endonasal access were 4.5 times greater than background (p = 0.01). Particles were typically large (> 75 µm), remained airborne for up to 10 s and travelled up to 1.1 m. Use of a microdebrider generated mean aerosol concentrations 18 times above baseline (p = 0.005). High-speed drilling did not produce aerosols greater than baseline. Pituitary tumour resection generated mean aerosol concentrations less than background (p = 0.18). Surgical drape removal generated small and large particles in mean concentrations 6.4 times greater than background (p < 0.001). CONCLUSION: Intubation and extubation generate large amounts of small particles that remain suspended in air for long durations and disperse through theatre. Endonasal access and pituitary tumour resection generate smaller concentrations of larger particles which are airborne for shorter periods and travel shorter distances.

The cardiovascular effects of crystalloid administration in endoscopy patients.

Intravenous fluids are commonly administered for patients having colonoscopy despite relatively little data to support this practice. It is unclear what, if any, effect crystalloid administration has on stroke volume and cardiac output in patients who are fasting and have had bowel preparation agents. We aimed to assess the physiological effect of 10 ml/kg of crystalloid administration in colonoscopy patients on haemodynamic parameters including stroke volume, stroke volume variation and cardiac output, as measured with transthoracic echocardiography. Our secondary aims were to determine whether stroke volume variation predicted fluid responsiveness in gastrointestinal endoscopy patients and whether these haemodynamic measures are different in fasting patients with bowel preparation (colonoscopy patients) compared to fasting patients alone (gastroscopy patients). We recruited 54 patients having elective gastrointestinal endoscopy (25 colonoscopy, 29 gastroscopy). All patients had stroke volume, cardiac output and stroke volume variation measured with transthoracic echocardiography at baseline. In colonoscopy patients, stroke volume, cardiac output and stroke volume variation were remeasured after 10 ml/kg of intravenous crystalloid. Administration of 10 ml/kg of crystalloid increases stroke volume by 19.6 ml ( p < 0.00005) and cardiac output by 0.81 l/min ( p < 0.001). Stroke volume variation reduced from 23% to 14% after fluid administration ( p < 0.0011). The optimum threshold of stroke volume variation to predict fluid responsiveness was 21% with a sensitivity of 77.8% and specificity of 62.5%. Administration of 10 ml/kg of crystalloid increases stroke volume and cardiac output, and reduces stroke volume variation in fasting elective colonoscopy patients.

Optimisation of Perioperative Cardiovascular Management to Improve Surgical Outcome II (OPTIMISE II) trial: study protocol for a multicentre international trial of cardiac output-guided fluid therapy with low-dose inotrope infusion compared with usual care in patients undergoing major elective gastrointestinal surgery.

INTRODUCTION: Postoperative morbidity and mortality in older patients with comorbidities undergoing gastrointestinal surgery are a major burden on healthcare systems. Infections after surgery are common in such patients, prolonging hospitalisation and reducing postoperative short-term and long-term survival. Optimal management of perioperative intravenous fluids and inotropic drugs may reduce infection rates and improve outcomes from surgery. Previous small trials of cardiac-output-guided haemodynamic therapy algorithms suggested a modest reduction in postoperative morbidity. A large definitive trial is needed to confirm or refute this and inform widespread clinical practice. METHODS: The Optimisation of Perioperative Cardiovascular Management to Improve Surgical Outcome II (OPTIMISE II) trial is a multicentre, international, parallel group, open, randomised controlled trial. 2502 high-risk patients undergoing major elective gastrointestinal surgery will be randomly allocated in a 1:1 ratio using minimisation to minimally invasive cardiac output monitoring to guide protocolised administration of intravenous fluid combined with low-dose inotrope infusion, or usual care. The trial intervention will be carried out during and for 4 hours after surgery. The primary outcome is postoperative infection of Clavien-Dindo grade II or higher within 30 days of randomisation. Participants and those delivering the intervention will not be blinded to treatment allocation; however, outcome assessors will be blinded when feasible. Participant recruitment started in January 2017 and is scheduled to last 3 years, within 50 hospitals worldwide. ETHICS/DISSEMINATION: The OPTIMISE II trial has been approved by the UK National Research Ethics Service and has been approved by responsible ethics committees in all participating countries. The findings will be disseminated through publication in a widely accessible peer-reviewed scientific journal. TRIAL REGISTRATION NUMBER: ISRCTN39653756.

Electromagnetic field-induced stimulation of Bruton's tyrosine kinase.

Here we present evidence that exposure of DT40 lymphoma B-cells to low energy electromagnetic fields (EMF) results in activation of phospholipase C-gamma 2 (PLC-gamma2), leading to increased inositol phospholipid turnover. PLC-gamma2 activation in EMF-stimulated cells is mediated by stimulation of the Bruton's tyrosine kinase (BTK), a member of the Src-related TEC family of protein tyrosine kinases, which acts downstream of LYN kinase and upstream of PLC-gamma2. B-cells rendered BTK-deficient by targeted disruption of the btk gene did not show enhanced PLC-gamma2 activation in response to EMF exposure. Introduction of the wild-type (but not a kinase domain mutant) human btk gene into BTK-deficient B-cells restored their EMF responsiveness. Thus, BTK exerts a pivotal and mandatory function in initiation of EMF-induced signaling cascades in B-cells.

Stimulation of Src family protein-tyrosine kinases as a proximal and mandatory step for SYK kinase-dependent phospholipase Cgamma2 activation in lymphoma B cells exposed to low energy electromagnetic fields.

Here, we present evidence that exposure of DT40 lymphoma B cells to low energy electromagnetic field (EMF) results in a tyrosine kinase-dependent activation of phospholipase Cgamma2 (PLC-gamma2) leading to increased inositol phospholipid turnover. B cells rendered PLC-gamma2-deficient by targeted disruption of the PLC-gamma2 gene as well as PLC-gamma2-deficient cells reconstituted with Src homology domain 2 (SH2) domain mutant PLC-gamma2 did not show any increase in inositol-1,4,5-trisphosphate levels after EMF exposure, providing direct evidence that PLC-gamma2 is responsible for EMF-induced stimulation of inositol phospholipid turnover, and its SH2 domains are essential for this function. B cells rendered SYK-deficient by targeted disruption of the syk gene did not show PLC-gamma2 activation in response to EMF exposure. The C-terminal SH2 domain of SYK kinase is essential for its ability to activate PLC-gamma2. SYK-deficient cells reconstituted with a C-terminal SH2 domain mutant syk gene failed to elicit increased inositol phospholipid turnover after EMF exposure, whereas SYK-deficient cells reconstituted with an N-terminal SH2 domain mutant syk gene showed a normal EMF response. LYN kinase is essential for the initiation of this biochemical signaling cascade. Lymphoma B cells rendered LYN-deficient through targeted disruption of the lyn gene did not elicit enhanced inositol phospholipid turnover after EMF exposure. Introduction of the wild-type (but not a kinase domain mutant) mouse fyn gene into LYN-deficient B cells restored their EMF responsiveness. B cells reconstituted with a SH2 domain mutant fyn gene showed a normal EMF response, whereas no increase in inositol phospholipid turnover in response to EMF was noticed in LYN-deficient cells reconstituted with a SH3 domain mutant fyn gene. Taken together, these results indicate that EMF-induced PLC-gamma2 activation is mediated by LYN-regulated stimulation of SYK, which acts downstream of LYN kinase and upstream of PLC-gamma2.