Intraoperative near infrared fluorescence guided identification of the ureters using low dose methylene blue: A first in human experience

Purpose: Near infrared fluorescence imaging is a promising technique that offers real-time visual information during surgery. In this study we report the first clinical results to our knowledge of ureteral imaging using near infrared fluorescence after a simple peripheral infusion of methylene blue. Furthermore, we assessed the optimal timing and dose of methylene blue. Materials and Methods: A total of 12 patients who underwent lower abdominal surgery were included in this prospective feasibility study. Near infrared fluorescence imaging was performed using the Mini-FLARE™ imaging system. To determine optimal timing and dose, methylene blue was injected intravenously at doses of 0.25, 0.5 or 1 mg/kg after exposure of the ureters. Imaging was performed for up to 60 minutes after injection. Results: In all patients both ureters could be clearly visualized within 10 minutes after infusion of methylene blue. The signal lasted at least up to 60 minutes after injection. The mean signal-to-background ratio of the ureter was 2.27 ± 1.22 (4), 2.61 ± 1.88 (4) and 3.58 ± 3.36 (4) for the 0.25, 0.5 and 1 mg/kg groups, respectively. A mixed model analysis was used to compare signal-to-background ratios among dose groups and times, and to assess the relationship between dose and time. A significant difference among time points (p <0.001) was found. However, no difference was observed among dose groups (p = 0.811). Conclusions: This study demonstrates the first successful use of near infrared fluorescence using low dose methylene blue for the identification of the ureters during lower abdominal surgery. © 2013 American Urological Association Education and Research, Inc

Intraoperative near-infrared fluorescence imaging of parathyroid adenomas with use of low-dose methylene blue

Background. Intraoperative identification of parathyroid adenomas can be challenging. We hypothesized that low-doses methylene blue (MB) and near-infrared fluorescence (NIRF) imaging could be used to identify parathyroid adenomas intraoperatively. Methods. MB was injected intravenously after exploration at a dose of 0.5 mg/kg into 12 patients who underwent parathyroid surgery. NIRF imaging was performed using the Mini-FLARE imaging system. Results. In 10 of 12 patients, histology confirmed a parathyroid adenoma. In 9 of these patients, NIRF could clearly identify the parathyroid adenoma during surgery. Seven of these 9 patients had a positive preoperative 99mTc-sestamibi single photon emission CT (SPECT) scan. Importantly, in 2 patients, parathyroid adenomas could be identified only using NIRF. Conclusion. This is the first study to show that low-dose MB can be used as NIRF tracer for identification of parathyroid adenomas, and suggests a correlation with preoperative 99mTc-sestamibi SPECT scanning. © 2013 Wiley Periodicals, Inc

Optimization of near-infrared fluorescence cholangiography for open and laparoscopic surgery

Background: During laparoscopic cholecystectomy, common bile duct (CBD) injury is a rare but severe complication. To reduce the risk of injury, near-infrared (NIR) fluorescent cholangiography using indocyanine green (ICG) has recently been introduced as a novel method of visualizing the biliary system during surgery. To date, several studies have shown feasibility of this technique; however, liver background fluorescence remains a major problem during fluorescent cholangiography. The aim of the current study was to optimize ICG dose and timing for NIR cholangiography using a quantitative intraoperative camera system during open hepatopancreatobiliary (HPB) surgery. Subsequently, these results were validated during laparoscopic cholecystectomy using a laparoscopic fluorescence imaging system. Methods: Twenty-seven patients who underwent NIR imaging using the Mini-FLARE image-guided surgery system during open HPB surgery were analyzed to assess optimal dosage and timing of ICG administration. ICG was intravenously injected preoperatively at doses of 5, 10, and 20 mg, and imaged at either 30 min (early) or 24 h (delayed) post-injection. Next, the optimal doses found for early and delayed imaging were applied to two groups of seven patients (n = 14) undergoing laparoscopic NIR fluorescent cholangiography during laparoscopic cholecystectomy. Results: Median liver-to-background contrast was 23.5 (range 22.1-35.0), 16.8 (range 11.3-25.1), 1.3 (range 0.7-7.8), and 2.5 (range 1.3-3.6) for 5 mg/30 min, 10 mg/30 min, 10 mg/24 h, and 20 mg/24 h, respectively. Fluorescence intensity of the liver was significantly lower in the 10 mg delayed-imaging dose group compared with the early imaging 5 and 10 mg dose groups (p = 0.001), which resulted in a significant increase in CBD-to-liver contrast ratio compared with the early administration groups (p < 0.002). These findings were qualitatively confirmed during laparoscopic cholecystectomy. Conclusion: This study shows that a prolonged interval between ICG administration and surgery permits optimal NIR cholangiography with minimal liver background fluorescence. © 2013 Springer Science+Business Media

Effect of general anaesthesia on functional outcome in patients with anterior circulation ischaemic stroke having endovascular thrombectomy versus standard care: a meta-analysis of individual patient data

Background: General anaesthesia (GA) during endovascular thrombectomy has been associated with worse patient outcomes in observational studies compared with patients treated without GA. We assessed functional outcome in ischaemic stroke patients with large vessel anterior circulation occlusion undergoing endovascular thrombectomy under GA, versus thrombectomy not under GA (with or without sedation) versus standard care (ie, no thrombectomy), stratified by the use of GA versus standard care. Methods: For this meta-analysis, patient-level data were pooled from all patients included in randomised trials in PuMed published between Jan 1, 2010, and May 31, 2017, that compared endovascular thrombectomy predominantly done with stent retrievers with standard care in anterior circulation ischaemic stroke patients (HERMES Collaboration). The primary outcome was functional outcome assessed by ordinal analysis of the modified Rankin scale (mRS) at 90 days in the GA and non-GA subgroups of patients treated with endovascular therapy versus those patients treated with standard care, adjusted for baseline prognostic variables. To account for between-trial variance we used mixed-effects modelling with a random effect for trials incorporated in all models. Bias was assessed using the Cochrane method. The meta-analysis was prospectively designed, but not registered. Findings: Seven trials were identified by our search; of 1764 patients included in these trials, 871 were allocated to endovascular thrombectomy and 893 were assigned standard care. After exclusion of 74 patients (72 did not undergo the procedure and two had missing data on anaesthetic strategy), 236 (30%) of 797 patients who had endovascular procedures were treated under GA. At baseline, patients receiving GA were younger and had a shorter delay between stroke onset and randomisation but they had similar pre-treatment clinical severity compared with patients who did not have GA. Endovascular thrombectomy improved functional outcome at 3 months both in patients who had GA (adjusted common odds ratio (cOR) 1·52, 95% CI 1·09–2·11, p=0·014) and in those who did not have GA (adjusted cOR 2·33, 95% CI 1·75–3·10, p&lt;0·0001) versus standard care. However, outcomes were significantly better for patients who did not receive GA versus those who received GA (covariate-adjusted cOR 1·53, 95% CI 1·14–2·04, p=0·0044). The risk of bias and variability between studies was assessed to be low. Interpretation: Worse outcomes after endovascular thrombectomy were associated with GA, after adjustment for baseline prognostic variables. These data support avoidance of GA whenever possible. The procedure did, however, remain effective versus standard care in patients treated under GA, indicating that treatment should not be withheld in those who require anaesthesia for medical reasons