Local anaesthetics: Theoretical aspects

Local anaesthetics are frequently used in both primary and secondary care. These agents transiently reduce the nervous conduction of nociceptive signals, reducing sensations of pain. In primary care, local anaesthetics are often used for minor surgical procedures. However, there are other uses for these agents. It is important to understand the issues encountered when using local anaesthetics in primary care. This review will cover clinical use, relevant pharmacology and adverse effects of the different local anaesthetic preparations.

A Phase IV, Multicenter, Open-Label Study of Emicizumab Prophylaxis in Persons with Hemophilia a with or without FVIII Inhibitors Undergoing Minor Surgical Procedures

Introduction: Emicizumab is a subcutaneously administered, bispecific, humanized monoclonal antibody that bridges factor (F)IXa and FX to restore the function of missing activated FVIII in persons with hemophilia A (PwHA). This study (NCT03361137) was designed to evaluate the safety and efficacy of emicizumab prophylaxis in PwHA with or without FVIII inhibitors undergoing minor surgical procedures without additional prophylaxis with bypassing agents (BPAs; for patients with FVIII inhibitors) or FVIII (for patients without FVIII inhibitors). Methods: This Phase IV, multicenter, single-arm, open-label study enrolled PwHA of any age, with or without FVIII inhibitors, who were scheduled to undergo minor surgical procedures. Patients were required to have received a minimum of four loading doses of emicizumab (3mg/kg once weekly for 4 weeks) prior to surgical procedure; subsequent maintenance doses of emicizumab were 1.5mg/kg once weekly, 3mg/kg every 2 weeks, or 6mg/kg every 4 weeks. Patients were required to be adherent to emicizumab prophylaxis. Treatment with emicizumab was scheduled to continue for at least 1 month after surgery. No other prophylactic treatment with coagulation factor was permitted. Outcome measures included incidence of excessive bleeding intra-operatively and until discharge from surgery, use of BPAs or FVIII to control bleeding (intra- and post-operatively), incidence of adverse events (AEs), and the percentage of patients with complications requiring hospitalization or return to surgery. Excessive bleeding was defined as a rating of fair to poor on the hemostatic rating scale and translates to an intra- and/or post-operative blood loss of ≥25% over expectation for a patient without hemophilia prior to discharge from surgery. Patients were followed for 28 days following discharge from surgery. Results: Between June 28, 2018 and March 13, 2020, 14 PwHA undergoing minor surgeries were enrolled (with FVIII inhibitors n=11; without FVIII inhibitors n=3); one PwHA with FVIII inhibitors enrolled but did not have surgery and discontinued prematurely, therefore the surgery analysis population comprised 13 patients (with FVIII inhibitors n=10; without FVIII inhibitors n=3). The majority (78.6%) of those enrolled were <18 years of age and all surgeries were either central venous access device (CVAD) removal (n=11) or dental procedures (n=2; Table 1). Of the 10 patients with FVIII inhibitors, one CVAD removal led to excessive bleeding during surgery with a need for BPA therapy, two patients undergoing CVAD removal received BPA therapy during surgery but had no reported excessive bleeding, three (two CVAD removals, one dental extraction) had post-operative bleeding that required use of a BPA (Table 2). Seven patients with FVIII inhibitors had zero bleeds after discharge from surgery. None of the three PwHA without FVIII inhibitors had excessive bleeding necessitating FVIII treatment during surgery or until discharge; two CVAD removals resulted in zero bleeds post-operatively and one dental extraction led to a post-operative bleed that did not require treatment. No serious AEs, thromboembolic events (TEs), thrombotic microangiopathies (TMAs) or deaths were reported during the study. Overall, 10 AEs occurred in five patients with FVIII inhibitors (headache n=3, limb injury, procedural pain, pyrexia, constipation, device occlusion, adhesiolysis, and hematoma, all n=1); no AEs were reported in patients without FVIII inhibitors. There were no AEs leading to dose modification, interruption or withdrawal of treatment, and no patient in either group had surgical complications requiring hospitalization or a return to surgery. The study was terminated early due to low enrollment and the limited variety of surgery types. Conclusions: In this study of mostly pediatric PwHA with and without FVIII inhibitors receiving emicizumab prophylaxis, minor surgeries were safely performed. The majority of surgeries were performed without additional prophylactic coagulation factor, however the small sample size should be considered here. There were no serious AEs, TEs, TMAs, or deaths. These findings are consistent with results from previous studies of patients undergoing minor surgery while receiving emicizumab prophylaxis. Disclosures Escobar: National Hemophilia Foundation: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees. Dunn:Genentech, Inc.: Consultancy; Nationwide Children's Hospital: Current Employment; World Federation of Hemophilia USA: Membership on an entity's Board of Directors or advisory committees; Medscape: Honoraria; Spire: Honoraria; ATHN: Research Funding; Takeda: Research Funding; BioMarin: Research Funding; uniQure: Consultancy. Quon:Octapharma: Honoraria; Bayer: Honoraria; Biomarin: Honoraria, Speakers Bureau; Bioverativ/Sanofi: Honoraria, Speakers Bureau; Genentech, Inc./F. Hoffmann-La Roche Ltd: Honoraria, Speakers Bureau; Novo Nordisk: Honoraria, Speakers Bureau; Shire/Takeda: Speakers Bureau; Orthopaedic Institute for Children: Current Employment. Trzaskoma:Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months. Lee:Genentech, Inc.: Current Employment; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company. Ko:Genentech, Inc.: Current Employment; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company. Carpenter:Novo Nordisk: Honoraria; Genentech, Inc.: Honoraria; American Thrombosis and Hemostasis Network: Membership on an entity's Board of Directors or advisory committees; CSL Behring: Research Funding; Shire: Research Funding; Hemostasis & Thrombosis Research Society: Membership on an entity's Board of Directors or advisory committees; American Academy of Pediatrics: Other: PREP Heme/Onc editorial board; Kedrion: Honoraria.

Evaluation of Different Positive End-Expiratory Pressures Using Supreme™ Airway Laryngeal Mask during Minor Surgical Procedures in Children

Background and objectives: The laryngeal mask is the method of choice for airway management in children during minor surgical procedures. There is a paucity of data regarding optimal management of mechanical ventilation in these patients. The Supreme™ airway laryngeal mask offers the option to insert a gastric tube to empty the stomach contents of air and/or gastric juice. The aim of this investigation was to evaluate the impact of positive end-expiratory positive pressure (PEEP) levels on ventilation parameters and gastric air insufflation during general anesthesia in children using pressure-controlled ventilation with laryngeal mask. Materials and Methods: An observational trial was carried out in 67 children aged between 1 and 11 years. PEEP levels of 0, 3 and 5 mbar were tested for 5 min in each patient during surgery and compared with ventilation parameters (dynamic compliance (mL/cmH2O), etCO2 (mmHg), peak pressure (mbar), tidal volume (mL), respiratory rate (per minute), FiO2 and gastric air (mL)) were measured at each PEEP. Air was aspirated from the stomach at the start of the sequence of measurements and at the end. Results: Significant differences were observed for the ventilation parameters: dynamic compliance (PEEP 5 vs. PEEP 3: p < 0.0001, PEEP 5 vs. PEEP 0: p < 0.0001, PEEP 3 vs. PEEP 0: p < 0.0001), peak pressure (PEEP 5 vs. PEEP 3: p < 0.0001, PEEP 5 vs. PEEP 0: p < 0.0001, PEEP 3 vs. PEEP 0: p < 0.0001) and tidal volume (PEEP 5 vs. PEEP 3: p = 0.0048, PEEP 5 vs. PEEP 0: p < 0.0001, PEEP 3 vs. PEEP 0: p < 0.0001). All parameters increased significantly with higher PEEP, with the exception of etCO2 (significant decrease) and respiratory rate (no significant difference). We also showed different values for air quantity in the comparisons between the different PEEP levels (PEEP 5: 2.8 ± 3.9 mL, PEEP 3: 1.8 ± 3.0 mL; PEEP 0: 1.6 ± 2.3 mL) with significant differences between PEEP 5 and PEEP 3 (p = 0.0269) and PEEP 5 and PEEP 0 (p = 0.0209). Conclusions: Our data suggest that ventilation with a PEEP of 5 mbar might be more lung protective in children using the Supreme™ airway laryngeal mask, although gastric air insufflation increased with higher PEEP. We recommend the use of a laryngeal mask with the option of inserting a gastric tube to evacuate potential gastric air.

Preoperative Antibiotic Prophylaxis in Elective Minor Surgical Procedures among Adults in Southern Italy

Little is known regarding the factors associated with surgical antibiotic prophylaxis (SAP) compliance in elective minor surgery. The purposes of this cross-sectional study were to identify the frequency of inappropriate SAP administration and to understand the characteristics associated with such inappropriateness in a sample of elective minor surgical procedures. The study was performed between May and July 2019 among a random sample of patients aged 18 years and older in seven public hospitals randomly selected in the Campania and Calabria Regions of Italy. Globally, only 45% of SAP approaches were deemed completely in accordance with the evidence-based guidelines. Patients with an ordinary admission, those who underwent local anesthesia, those receiving plastic and reconstructive and ophthalmology surgery, and those who had not received a prosthetic implant were more likely to receive an appropriate SAP approach; those receiving obstetrics, gynecological, and urological surgical procedures were less likely than those who underwent abdominal, vascular, and breast surgery. The course of antibiotic prophylaxis was not consistent with the guidelines in 48.5% procedures with one or more reasons for inappropriateness. Appropriate time of the SAP administration was more frequently observed in patients who were older, those with a Charlson comorbidity index of 0, those who did not receive a prosthetic implant, and those receiving plastic and reconstructive surgery; it was less likely in patients receiving obstetrics, gynecological, and urological surgeries compared with those who underwent abdominal, vascular, and breast surgery. Aspects of SAP that need to be improved are molecule choice, time of administration, and specific surgical procedures. Hospital managers should involve surgeons and anesthesiologists in initiatives tailored to optimize SAP prescribing.

A Study on Role of Follow up in Minor Surgical Procedures

Background: Minor surgical procedures are surgeries that can be performed in the clinic under local anesthesia and doesn’t require preoperative and postoperative admission. In most of the institutions in our country, we advised patients to follow up within 7 to 10 days following minor surgical procedures. Unnecessary follow up increases stress to the patients in terms of not being able to manage daily routine work and would be costly as well. As a General Practitioner, majority of the cases done are the minor surgical procedures. Methods: The study was a prospective cross sectional study conducted in General Surgery Department at United Mission Hospital, Palpa from Dec 2013 to May 2013. 228 patients were divided in two groups of “No follow up” group and “Follow-up” group. No Follow-up Group was asked pre-formed questionnaires by telephone where as Follow-up group were asked to follow up routinely on day 7 to 10 days of surgery and asked the same questions. Statistical analysis was done using SPSS program and Microsoft excel. P value of <0.05 was considered statistically significant. P-value was determined by using Chi Square test. Result: The overall wound infection among 228 patients was found to be 14.5 percent with infection rate of 16.4 percent in No Follow up group and 12.7 percent in Follow-up group. The infection rate was found to be higher among the older age group of patient maximum being 36.4% in the age group of 50-59 years with p value of 0.053. Other risk factors like age, sex, residence, duration of surgery, socio economic status, history of medical illness and BMI didn’t have significant association with rate of infection following minor surgical procedure. Conclusion: The routine postoperative follow up in minor surgery is unnecessary unless there are any signs suggestive of infection.