Good clinical research practice (GCRP) in pharmacodynamic studies of neuromuscular blocking agents III: The 2023 Geneva revision

The set of guidelines for good clinical research practice in pharmacodynamic studies of neuromuscular blocking agents was developed following an international consensus conference in Copenhagen in 1996 (Viby-Mogensen et al., Acta Anaesthesiol Scand 1996, 40 , 59–74); the guidelines were later revised and updated following the second consensus conference in Stockholm in 2005 (Fuchs-Buder et al., Acta Anaesthesiol Scand 2007, 51 , 789–808). In view of new devices and further development of monitoring technologies that emerged since then, (e.g., electromyography, three-dimensional acceleromyography, kinemyography) as well as novel compounds (e.g., sugammadex) a review and update of these recommendations became necessary. The intent of these revised guidelines is to continue to help clinical researchers to conduct high-quality work and advance the field by enhancing the standards, consistency, and comparability of clinical studies. There is growing awareness of the importance of consensus-based reporting standards in clinical trials and observational studies. Such global initiatives are necessary in order to minimize heterogeneous and inadequate data reporting and to improve clarity and comparability between different studies and study cohorts. Variations in definitions of endpoints or outcome variables can introduce confusion and difficulties in interpretation of data, but more importantly, it may preclude building of an adequate body of evidence to achieve reliable conclusions and recommendations. Clinical research in neuromuscular pharmacology and physiology is no exception.     

Effects of reduction of carrier gas flow rate on sevoflurane and isoflurane consumption and costs

Purpose To evaluate whether sevoflurane and isoflurane consumption would be actually halved by halving the carrier gas flow rate, as predicted by a theoretical model, we measured the consumed volume of liquid sevoflurane and isoflurane and total costs of anesthetic gas at carrier gas flow rates of 3 and 61·min⁻¹. Methods Eighty patients of ASA physical status I or II were randomly assigned to one of four groups: sevoflurane at 3 or 61·min⁻¹ and isoflurane at 3 or 61·min⁻¹. Anesthesia was induced with thiamylal and maintained with sevoflurane or isoflurane, as well as with nitrous oxide in oxygen. The consumption of sevoflurane and isoflurane was measured by weighing the bottle of liquid agent, which was greater in the groups receiving 61·min⁻¹ gas than in those receiving 31·min⁻¹. Results Halving the carrier gas flow rate reduced the consumption of sevoflurane by 41.8% and that of isoflurane by 52.6%. It also reduced the total cost by 44.3% for sevoflurane and 49.2% for isoflurane. Conclusion Halving the carrier gas flow rates halved the consumption of isoflurane but not of sevoflurane, indicating that factors other than carrier gas flow rates are involved in determining consumption in the clinical setting.     

Successful surgery for an acute type A aortic dissection following repair of a descending thoracic aortic aneurysm

Acute type A aortic dissection in the presence of a previously repaired atherosclerotic descending thoracic aortic aneurysm is rarely reported. We experienced a patient who underwent an ascending aortic replacement with reconstruction of the aortic arch 16 months after repair of a descending thoracic aortic aneurysm. We succeeded in the redo operation with comprehensive techniques involving selective cerebral perfusion, deep hypothermia, early antegrade systemic circulation for cerebral protection, and femoro-femoral bypass with occlusion of the descending aorta for lower systemic perfusion as well as renal perfusion. The patient recovered and is doing well one year after the redo operation.     

Status of Involved Lymph Nodes and Direction of Metastatic Lymphatic Flow Between Submucosal and T2-4 Thoracic Squamous Cell Esophageal Cancers

Background  Three-field lymph node dissection for thoracic esophageal cancer is associated with high morbidity and reduced quality of life after surgery. Consequently, minimized lymphadenectomy would be desirable, if appropriate. In the present study, we retrospectively analyzed the status of involved nodes and the direction of metastatic lymphatic flow from tumors into involved nodes to determine whether submucosal squamous cell esophageal cancers are potential candidates for minimized lymphadenectomy. Methods  We enrolled 199 patients who received esophagectomy with extensive lymph node dissection between 1989 and 2005 and retrospectively analyzed their prognoses, distribution of solitary metastatic lymph nodes, and the direction of metastatic lymphatic flow from the tumor, taking into consideration tumor location and depth. Results  Of these patients with submucosal cancers, 83% had 1 or 2 involved nodes, and their esophageal cancer-specific 5-year survival rate was 66%. Solitary lymph node metastasis did not occur in neck lymph nodes in lower thoracic submucosal esophageal cancers, and the direction of metastatic lymphatic flow from the tumor was almost always in one direction. By contrast, T2–4 cancers with 2–4 involved nodes had bidirectional metastatic lymphatic flow from the tumor. Conclusions  There was a difference in the status of lymph node metastasis and the direction of metastatic lymphatic flow from tumors into involved nodes between submucosal and T2–4 thoracic squamous cell esophageal cancers. This analysis may be useful for developing an approach to minimized lymphadenectomy for thoracic esophageal cancers.     

Adrenomedullin reflects cardiac dysfunction, excessive blood volume, and inflammation in hemodialysis patients

BACKGROUND: Plasma adrenomedullin (AM) reflects cardiac dysfunction and predicts survival after myocardial infarction. The present study was designed to investigate whether the mature AM (mAM) reflects status of cardiac function, systemic blood volume, or inflammation in hemodialysis patients with cardiovascular disease, and whether mortality and additional cardiovascular morbidity can be predicted by mAM. METHODS: Plasma levels of mAM, atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), norepinephrine (NE), and C-reactive protein (CRP) before hemodialysis were measured in 67 chronic hemodialysis patients with cardiovascular disease, along with 2-dimensional and Doppler echocardiographic variables. RESULTS: By univariate regression analysis, mAM correlated negatively with pulmonary venous flow velocity ratio and left ventricular (LV) ejection fraction and positively with LV inflow velocity ratio, LV end-diastolic, end-systolic volume indexes, plasma CRP level, and removal fluid volume by ultrafiltration. Multivariate stepwise regression analysis revealed that mAM reflected all variables better than log [ANP], log [BNP], and log [NE]. During a 1-year follow-up period, 7 patients died and 8 had additional cardiovascular events. Event-free Kaplan-Meier curves based on the median mAM (4.55 pmol/L) showed that patients with high plasma mAM levels had higher mortality and morbidity than those with low plasma mAM levels (P = 0.0056). By Cox multivariate proportional hazard analysis, mAM was related to mortality and morbidity [hazard ratio (HR) 4.55, 95% CI 1.2-16.8, P= 0.023). CONCLUSION: Plasma mAM reflects cardiac dysfunction, excessive blood volume, and inflammation better than ANP, BNP, and NE, resulting in a predictor of mortality and cardiovascular morbidity in hemodialysis patients with cardiovascular disease.     

The frontal cortex is activated during learning of endoscopic procedures

Background

To date, several training and evaluation systems for endoscopic surgery have been developed, such as virtual-reality simulators and box trainers. However, despite current advances in these objective assessments, no functional brain studies during learning of endoscopic surgical skills have been carried out. In the present study, we investigated cortical activation using near-infrared spectroscopy (NIRS) during endoscopic surgical tasks.

Study design

A total of 21 right-handed subjects, comprising 4 surgical experts, 4 trainees, and 13 novices, participated in the study. Suturing and knot-tying tasks were performed in a box trainer. Cortical activation was assessed in all subjects by task-related changes in hemoglobin (Hb) oxygenation using NIRS.

Results

In surgical experts and novices with no experience of endoscopic surgical training, we found no changes in oxy-Hb, deoxy-Hb or total-Hb levels in any of the frontal channels. In surgical trainees and one novice with experience of endoscopic surgical training, we found significant increases in oxy-Hb and total-Hb levels in most of the frontal channels. There were significant differences in oxy-Hb and total-Hb levels in CH-19 between surgical experts and trainees (p = 0.02 for both), and between surgical trainees and novices with no experience of endoscopic surgical training (p = 0.008 for both). Furthermore, additional training increased oxy-Hb levels in the frontal cortex of novices with no experience of endoscopic surgical training but had no such effect on surgical experts.

Conclusions

The present data suggest that NIRS is a feasible tool for assessing brain activation during endoscopic surgical tasks, and may have a large impact on the future development of teaching, training, and assessment methods for endoscopic surgical skills.     

Respiratory-gated F-FDG PET/CT for the diagnosis of liver metastasis

Purpose

To ascertain the role of respiratory-gated PET/CT with ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) for accurate diagnosis of liver metastasis.

Materials and methods

Forty patients with suspected liver metastasis underwent conventional whole-body PET/CT scan initially, followed by respiratory-gated PET/CT scan covering the liver. Visual detectability (using a 5-point confidence scale), maximum standardized uptake value (SUVmax) and metabolic tumor volume (MTV) of hepatic metastatic lesions were assessed for three data sets including ordinary whole-body (WB) scan, and non-respiratory-gated (nRG) and respiratory-gated (RG) scans. Results of enhanced CT and/or MRI, or clinical and radiological follow-up were used for reference.

Results

Sixteen of the patients were found to have 53 metastatic lesions in the liver. Patient-based accuracy of WB, nRG, and RG was 92.5%, 95.0%, and 97.5%, respectively, with a lesion-based detection rate of 67.9%, 73.6%, and 73.6%, respectively. The average SUVmax of 34 liver metastatic lesions for WB, nRG, and RG was 6.60 ± 2.34, 7.19 ± 2.66, and 8.08 ± 3.24, respectively. SUVmax for RG was significantly higher than that for WB (p = 0.0069). The average MTV of these 40 lesions for the three protocols was 5.32 ± 4.78 cm³, 5.07 ± 4.73 cm³, and 4.73 ± 4.67 cm³, respectively. Among the three protocols, RG showed the best visual and quantitative evaluation for diagnosis of liver metastasis.

Conclusion

Respiratory-gated PET/CT allows more accurate identification of liver metastases than non-respiratory-gated PET/CT.     

Cardiovascular applications of magnetic resonance flow and velocity measurements

With recent developments of MR techniques for blood flow measurements, qualitative and quantitative information on both flow volume and flow velocity in the major vessels can be obtained. MR flow quantitation uses the phase, rather than the amplitude of the MR signal, to reconstruct the images. Previous validation studies have demonstrated the accuracy of the phase shift techniques for measuring flow velocities. This technique is now being applied successfully in the cardiovascular system to quantify global and regional ventricular function, valvular heart disease, pulmonary artery disease, thoracic aortic disease, congenital heart disease, and ischemic heart disease.     

Improved reproducibility in measuring LV volumes and mass using multicoil breath-hold cine MR imaging

There is a generally recognized need for improvement in quality of fast cardiac MR images. Consequently, breath-hold cine MR images were obtained with multiple surface coils connected to phased array receivers, and C/N, intra-observer and inter-observer variabilities for LV volumes and mass were evaluated. Two sets of short-axis images of the LV, one with multiple surface coils and another with a body coil, were acquired in eight subjects with a fast cine MR sequence using k-space segmentation (TR/TE=7/2.2 msec, temporal resolution=56 msec). C/N with multicoil imaging was 32.2 ± 7.6 (mean ± SD), significantly higher than that with a body coil (11.0 ± 3.3, P < .01). The mean percentage differences in intra-observer and inter-observer measurements with multicoil imaging were significantly better than those with a body coil. In conclusion, multicoil imaging provides significant gain in C/N on breath-hold cine MRI of the heart. In addition, intra-observer and inter-observer reproducibilities are improved with multicoil imaging.