DrugBank 6.0: the DrugBank Knowledgebase for 2024First released in 2006, DrugBank (https://go.drugbank.com) has grown to become the 'gold standard' knowledge resource for drug, drug-target and related pharmaceutical information. DrugBank is widely used across many diverse biomedical research and clinical applications, and averages more than 30 million views/year. Since its last update in 2018, we have been actively enhancing the quantity and quality of the drug data in this knowledgebase. In this latest release (DrugBank 6.0), the number of FDA approved drugs has grown from 2646 to 4563 (a 72% increase), the number of investigational drugs has grown from 3394 to 6231 (a 38% increase), the number of drug-drug interactions increased from 365 984 to 1 413 413 (a 300% increase), and the number of drug-food interactions expanded from 1195 to 2475 (a 200% increase). In addition to this notable expansion in database size, we have added thousands of new, colorful, richly annotated pathways depicting drug mechanisms and drug metabolism. Likewise, existing datasets have been significantly improved and expanded, by adding more information on drug indications, drug-drug interactions, drug-food interactions and many other relevant data types for 11 891 drugs. We have also added experimental and predicted MS/MS spectra, 1D/2D-NMR spectra, CCS (collision cross section), RT (retention time) and RI (retention index) data for 9464 of DrugBank's 11 710 small molecule drugs. These and other improvements should make DrugBank 6.0 even more useful to a much wider research audience ranging from medicinal chemists to metabolomics specialists to pharmacologists.
Residual Paralysis at the Time of Tracheal ExtubationIn Brief Respiratory and pharyngeal muscle function are impaired during minimal neuromuscular blockade. Tracheal extubation in the presence of residual paresis may contribute to adverse respiratory events. In this investigation, we assessed the incidence and severity of residual neuromuscular block at the time of tracheal extubation. One-hundred-twenty patients presenting for gynecologic or general surgical procedures were enrolled. Neuromuscular blockade was maintained with rocuronium (visual train-of-four [TOF] count of 2) and all subjects were reversed with neostigmine at a TOF count of 2–4. TOF ratios were quantified using acceleromyography immediately before tracheal extubation, after clinicians had determined that complete neuromuscular recovery had occurred using standard clinical criteria (5-s head lift or hand grip, eye opening on command, acceptable negative inspiratory force or vital capacity breath values) and peripheral nerve stimulation (no evidence of fade with TOF or tetanic stimulation). TOF ratios were measured again on arrival to the postanesthesia care unit. Immediately before tracheal extubation, the mean TOF ratio was 0.67 ± 0.2; among the 120 patients, 70 (58%) had a TOF ratio <0.7 and 105 (88%) had a TOF ratio <0.9. Significantly fewer patients had TOF ratios <0.7 (9 subjects, 8%) and <0.9 (38 subjects, 32%) in the postanesthesia care unit compared with the operating room (P < 0.001). Our results suggest that complete recovery from neuromuscular blockade is rarely present at the time of tracheal extubation. IMPLICATIONS: We investigated the incidence and severity of residual paralysis at the time of tracheal extubation. When clinicians determined that full recovery of neuromuscular function had occurred and that the endotracheal tube could be safely removed, only 15 of 120 subjects had train-of-four ratios ≥0.9.
Postanesthesia Care Unit Recovery Times and Neuromuscular Blocking Drugs: A Prospective Study of Orthopedic Surgical Patients Randomized to Receive Pancuronium or RocuroniumUNLABELLED: In this study, we examined the effect of choice of neuromuscular blocking drug (NMBD) (pancuronium versus rocuronium) on postoperative recovery times and associated adverse outcomes in patients undergoing orthopedic surgical procedures. Seventy patients were randomly allocated to a pancuronium or rocuronium group. On arrival to the postanesthesia care unit (PACU) and again 30 min later, train-of-four ratios were quantified by using acceleromyography. Immediately after acceleromyographic measurements, patients were assessed for signs and symptoms of residual paresis. During the PACU admission, episodes of hypoxemia, nausea, and vomiting were recorded. The time required for patients to meet discharge criteria and the time of actual PACU discharge were noted. Forty percent of patients in the pancuronium group had train-of-four ratios <0.7 on arrival to the PACU, compared with only 5.9% of subjects in the rocuronium group (P < 0.001). Patients in the pancuronium group were more likely to experience symptoms of muscle weakness (blurry vision and generalized weakness; P < 0.001) and hypoxemia (10 patients in the rocuronium group versus 21 patients in the pancuronium group; P = 0.015) during the PACU admission. Significant delays in meeting PACU discharge criteria (50 min [45-60 min] versus 30 min [25-40 min]) and achieving actual discharge (70 min [60-90 min] versus 57.5 min [45-61 min]) were observed when the pancuronium group was compared with the rocuronium group (P < 0.001). In conclusion, our study indicates that PACU recovery times may be prolonged when long-acting NMBDs are used in surgical patients. IMPLICATIONS: Clinical recovery may be delayed in surgical patients administered long-acting neuromuscular blocking drugs. During the postanesthesia care unit admission, patients randomized to receive pancuronium (versus rocuronium) were more likely to exhibit symptoms of muscle weakness, develop hypoxemia, and require more time to meet discharge criteria.
Coagulation Tests, Blood Loss, and Transfusion Requirements in Platelet-Rich Plasmapheresed Versus Nonpheresed Cardiac Surgery PatientsThe results of several studies suggest that acute platelet-rich plasmapheresis decreases blood loss and allogeneic blood product transfusion requirements in cardiac surgery patients. We designed a randomized, prospective study to determine whether acute platelet-rich plasmapheresis decreases blood loss and allogeneic transfusion requirements in primary cardiac surgery patients. Forty patients were randomized to a control or pheresis group. The pheresis group had platelet-rich plasmapheresis performed before cardiopulmonary bypass (CPB) and the platelet-rich plasma (PRP) was returned after CPB. The control group was managed in the normal fashion without pheresis. All patients had serial coagulation studies, hemoglobin, and platelet counts determined intra- and postoperatively. Chest tube drainage and transfusion requirements were recorded. There were no differences in the coagulation tests, platelet counts, chest tube drainage, or allogeneic blood product transfusion requirements between the two groups at any time. The authors conclude that the use of acute platelet-rich plasmapheresis in primary cardiac surgery patients does not decrease chest tube drainage or the need for allogeneic blood transfusions.
Complications of Gold Weight Eyelid Implants for Treatment of Fifth and Seventh Nerve ParalysisComplications occurred in six patients after gold weights were implanted into the upper eyelid tissues for fifth and seventh nerve palsies. These complications included implant infection without extrusion (in one patient); entropion with trichiasis and presumed inflammatory reaction to the gold weight material (in one patient); upper eyelid distortion and poor eyelid contour with corneal ulceration and scarring (in one patient); significant residual lagophthalmos with exposure keratitis (in one patient); and blepharoptosis obscuring the pupillary access (in two patients). Resolution of the complications required 1. implant removal in four of six patients without reinsertion of a second weight, 2. recession of the retractors of the upper eyelids with medial and lateral canthoplasty (in four patients), and 3. permanent tarsorrhaphy (in one patient). The authors conclude that complications may be minimized by careful preoperative determination of the optimum implant size, weight, and placement within the eyelid as well as meticulous attention to the surgical technique of implantation. The use of other eyelid protective procedures is often necessary to augment corneal protection especially in patients with combined fifth and seventh cranial nerve palsies. Endogenous implant infection without extrusion of the gold weight may be distinguished from presumed inflammation due to gold allergy by clinical response to antibiotics in the former and requirements of steroids or removal of the implant in the latter.