Ipsilateral and Simultaneous Comparison of Responses from Acceleromyography- and Electromyography-based Neuromuscular Monitors.

BACKGROUND: The paucity of easy-to-use, reliable objective neuromuscular monitors is an obstacle to universal adoption of routine neuromuscular monitoring. Electromyography (EMG) has been proposed as the optimal neuromuscular monitoring technology since it addresses several acceleromyography limitations. This clinical study compared simultaneous neuromuscular responses recorded from induction of neuromuscular block until recovery using the acceleromyography-based TOF-Watch SX and EMG-based TetraGraph. METHODS: Fifty consenting patients participated. The acceleromyography and EMG devices analyzed simultaneous contractions (acceleromyography) and muscle action potentials (EMG) from the adductor pollicis muscle by synchronization via fiber optic cable link. Bland-Altman analysis described the agreement between devices during distinct phases of neuromuscular block. The primary endpoint was agreement of acceleromyography- and EMG-derived normalized train-of-four ratios greater than or equal to 80%. Secondary endpoints were agreement in the recovery train-of-four ratio range less than 80% and agreement of baseline train-of-four ratios between the devices. RESULTS: Acceleromyography showed normalized train-of-four ratio greater than or equal to 80% earlier than EMG. When acceleromyography showed train-of-four ratio greater than or equal to 80% (n = 2,929), the bias was 1.3 toward acceleromyography (limits of agreement, -14.0 to 16.6). When EMG showed train-of-four ratio greater than or equal to 80% (n = 2,284), the bias was -0.5 toward EMG (-14.7 to 13.6). In the acceleromyography range train-of-four ratio less than 80% (n = 2,802), the bias was 2.1 (-16.1 to 20.2), and in the EMG range train-of-four ratio less than 80% (n = 3,447), it was 2.6 (-14.4 to 19.6). Baseline train-of-four ratios were higher and more variable with acceleromyography than with EMG. CONCLUSIONS: Bias was lower than in previous studies. Limits of agreement were wider than expected because acceleromyography readings varied more than EMG both at baseline and during recovery. The EMG-based monitor had higher precision and greater repeatability than acceleromyography. This difference between monitors was even greater when EMG data were compared to raw (nonnormalized) acceleromyography measurements. The EMG monitor is a better indicator of adequate recovery from neuromuscular block and readiness for safe tracheal extubation than the acceleromyography monitor.

Consensus for the management of analgesia, sedation and delirium in adults with COVID-19-associated acute respiratory distress syndrome. / Consenso para el manejo de la analgesia, sedación y delirium en adultos con síndrome de distrés respiratorio agudo por COVID-19.

OBJECTIVE: To propose agile strategies for a comprehensive approach to analgesia, sedation, delirium, early mobility and family engagement for patients with COVID-19-associated acute respiratory distress syndrome, considering the high risk of infection among health workers, the humanitarian treatment that we must provide to patients and the inclusion of patients' families, in a context lacking specific therapeutic strategies against the virus globally available to date and a potential lack of health resources. METHODS: A nonsystematic review of the scientific evidence in the main bibliographic databases was carried out, together with national and international clinical experience and judgment. Finally, a consensus of recommendations was made among the members of the Committee for Analgesia, Sedation and Delirium of the Sociedad Argentina de Terapia Intensiva. RESULTS: Recommendations were agreed upon, and tools were developed to ensure a comprehensive approach to analgesia, sedation, delirium, early mobility and family engagement for adult patients with acute respiratory distress syndrome due to COVID-19. DISCUSSION: Given the new order generated in intensive therapies due to the advancing COVID-19 pandemic, we propose to not leave aside the usual good practices but to adapt them to the particular context generated. Our consensus is supported by scientific evidence and national and international experience and will be an attractive consultation tool in intensive therapies.

OBJETIVO: Proponer estrategias agile para este abordaje integral de la analgesia, sedación, delirium, implementación de movilidad temprana e inclusión familiar del paciente con síndrome de dificultad respiratoria aguda por COVID-19, considerando el alto riesgo de infección que existe entre los trabajadores de salud, el tratamiento humanitario que debemos brindar al paciente y su familia, en un contexto de falta estrategias terapéuticas específicas contra el virus globalmente disponibles a la fecha y una potencial falta de recursos sanitarios. METODOS: Se llevó a cabo una revision no sistemática de la evidencia científica en las principales bases de datos bibliográficos, sumada a la experiencia y juicio clínico nacional e internacional. Finalmente, se realizó un consenso de recomendaciones entre los integrantes del Comité de Analgesia, Sedación y Delirium de la Sociedad Argentina de Terapia Intensiva. RESULTADOS: Se acordaron recomendaciones y se desarrollaron herramientas para asegurar un abordaje integral de analgesia, sedación, delirium, implementación de movilidad temprana e inclusión familiar del paciente adulto con síndrome de dificultad respiratoria aguda por COVID-19. DISCUSIÓN: Ante el nuevo orden generado en las terapias intensivas por la progresión de la pandemia de COVID-19, proponemos no dejar atrás las buenas prácticas habituales, sino adaptarlas al contexto particular generado. Nuestro consenso está respaldado en la evidencia científica, la experiencia nacional e internacional, y será una herramienta de consulta atractiva en las terapias intensivas.

Evaluating a Quality Improvement Initiative to Increase Anesthesia Providers' Use of and Understanding of Quantitative Neuromuscular Monitors.

Improved understanding of the monitoring and dosing practices of anesthesia providers regarding neuromuscular blockade is necessary. The use of subjective methods such as peripheral nerve stimulation and clinical assessment tests can increase the risk of residual neuromuscular blockade and adverse postoperative outcomes. Quantitative monitoring of neuromuscular blockade is an alternative tool to peripheral nerve stimulation to guide neuromuscular blockade; however, it is rarely used by providers. We developed an initiative to improve anesthesia providers' knowledge of neuromuscular blockade pharmacology, physiology, monitoring, and management. After the initiative, an analysis assessed for practice change regarding the use of quantitative monitoring and dosing of neuromuscular blocking agents and neostigmine. The use of quantitative monitoring increased significantly from 14.0% in the preinitiative group to 48.0% after the initiative (P < .001). The least squares mean 95% effective dose (ED95) neuromuscular blocking agents dose was compared between pre-initiative and postinitiative groups, and case length was a significant predictor for patients receiving the highest neuromuscular blocking agents doses. Neostigmine doses were compared between preinitiative and postinitiative groups, and body mass index was a significant predictor of the least squares mean neostigmine dose (P = .002) and the likelihood of receiving a high neostigmine dose (odds ratio = 0.911, 95% CI = 0.870-0.955).

Deep vs. moderate neuromuscular blockade during laparoscopic surgery: A systematic review and meta-analysis.

BACKGROUND: Previous studies have reported that deep neuromuscular block (posttetanic-count 1 to 2 twitches) improves surgical conditions during laparoscopy compared with moderate block (train-of-four count: 1 to 2 twitches). However, comparisons of surgical conditions were made using different scales and assessment intervals with variable results. OBJECTIVE: To explore the heterogeneity of previous comparisons between deep and moderate neuromuscular block. DESIGN: Systematic review and meta-analysis of randomised controlled trials (RCTs). DATA SOURCES: Medline, EMBASE and Cochrane Central Register of Controlled Trials were searched from inception to October 2017. ELIGIBILITY CRITERIA: Our meta-analysis included RCTs comparing the effects of deep with moderate neuromuscular block on surgical field conditions during laparoscopic surgery. The frequency of excellent or good operating conditions on a surgical rating scale was compared. Heterogeneity was assessed by subgroup analyses. RESULTS: Eleven RCTs involving 844 patients were included. On the surgical rating scale, the frequency of excellent or good operating conditions was higher with deep block compared with a moderate block (odds ratio 2.83, 95% confidence interval 1.34 to 5.99, P = 0.007, I = 59%). We analysed surgical rating according to the number of assessments made. There was a significant difference in surgical rating with multiple assessments, but no difference when the assessment was made on only one occasion. A significant difference in rating was noted with variable abdominal pressures; there was no significant difference with the same fixed abdominal pressure. Trial sequential analysis demonstrated that the cumulative z-curve crossed the O'Brien-Fleming significance boundary. However, required information size was not achieved. CONCLUSION: Deep block was associated with excellent or good surgical rating more frequently than moderate block. However, this finding was not consistent on subgroup analyses based on frequencies of assessment of surgical conditions and abdominal pressure. Further studies are required to address the heterogeneity and power shortage demonstrated by the trial sequential analysis.

Optimal neuromuscular blocking effects of remifentanil during tracheal intubation under general anesthesia.

Objective This study was performed to determine the effect of the remifentanil dose on the onset time of rocuronium with electromyography. Methods This retrospective comparative study included 75 patients undergoing general anesthesia for elective surgery. Patients received lidocaine (40 mg) and propofol (2 mg/kg) followed by rocuronium (0.6 mg/kg) with either saline infusion (Group S), remifentanil at 0.5 µg/kg/minute (Group R 0.5), or remifentanil at 1.0 µg/kg/minute (Group R 1.0). Neuromuscular block was monitored by train-of-four (TOF) electromyography, and the times taken to reach TOF 0 and TOF ratio (TOFR) 25% were recorded. Results The times taken to reach TOF 0 and TOFR 25% were significantly higher in Groups R 0.5 and R 1.0 than in Group S. The time taken to reach TOF 0 was 130.0 ± 6.4 s in Group S, 142.6 ± 6.0 s in Group R 0.5, and 183.0 ± 11.6 s in Group R 1.0. The time taken to reach TOFR 25% was also higher in Groups R 0.5 and R 1.0 than in Group S. Conclusions As the remifentanil dose increases, the intubation time required to reach TOF 0 also increases. Remifentanil has an effect on the onset of rocuronium.

Consensus Statement on Perioperative Use of Neuromuscular Monitoring.

A panel of clinician scientists with expertise in neuromuscular blockade (NMB) monitoring was convened with a charge to prepare a consensus statement on indications for and proper use of such monitors. The aims of this article are to: (a) provide the rationale and scientific basis for the use of quantitative NMB monitoring; (b) offer a set of recommendations for quantitative NMB monitoring standards; (c) specify educational goals; and (d) propose training recommendations to ensure proper neuromuscular monitoring and management. The panel believes that whenever a neuromuscular blocker is administered, neuromuscular function must be monitored by observing the evoked muscular response to peripheral nerve stimulation. Ideally, this should be done at the hand muscles (not the facial muscles) with a quantitative (objective) monitor. Objective monitoring (documentation of train-of-four ratio ≥0.90) is the only method of assuring that satisfactory recovery of neuromuscular function has taken place. The panel also recommends that subjective evaluation of the responses to train-of-four stimulation (when using a peripheral nerve stimulator) or clinical tests of recovery from NMB (such as the 5-second head lift) should be abandoned in favor of objective monitoring. During an interim period for establishing these recommendations, if only a peripheral nerve stimulator is available, its use should be mandatory in any patient receiving a neuromuscular blocking drug. The panel acknowledges that publishing this statement per se will not result in its spontaneous acceptance, adherence to its recommendations, or change in routine practice. Implementation of objective monitoring will likely require professional societies and anesthesia department leadership to champion its use to change anesthesia practitioner behavior.

Frequency of inadequate neuromuscular blockade during general anesthesia.

STUDY OBJECTIVE: We used electronic health record data to define frequency of inadequate intraoperative neuromuscular blockade (NMB). DESIGN: Retrospective observational study using electronic health record data. SETTING: Operating room in a tertiary care academic hospital. PATIENTS: A total of 129,209 adult patients with American Society of Anesthesiologists physical status 1 to 5 undergoing general anesthesia in an outpatient or inpatient setting who received nondepolarizing NMB. We excluded patients intubated before arrival to the operating room, patients undergoing a liver transplant or cardiac surgery, and patients who remained intubated at the end of the operation. INTERVENTIONS: None. MEASUREMENTS: The primary outcomes were inadequate NMB defined by (1) documentation of patient movement and (2) documentation of surgical request for additional NMB, followed by NMB agent administration. MAIN RESULTS: A total of 1261 patients (1.0%) demonstrated either intraoperative movement (369 or 0.29%) or prompted surgical request for additional NMB agent (921 or 0.71%). Trend analysis showed a variation in the annual rate of inadequate NMB, with an increase from 2004 to 2013 for criteria 1 and 2. CONCLUSIONS: Nearly 1% of all general anesthetic procedures involving NMB exhibit inadequate relaxation resulting in procedural interruption. These data suggest that current use of neuromuscular blocking drugs and NMB monitoring expose patients to inadequate blockade. The risk of this phenomenon warrants further study.

Recommendations on the use of deep neuromuscular blockade by anaesthesiologists and surgeons. AQUILES (Anestesia QUIrúrgica para Lograr Eficiencia y Seguridad) Consensus. / Recomendaciones sobre el uso de bloqueo neuromuscular profundo por parte de anestesiólogos y cirujanos. Consenso AQUILES (Anestesia QUIrúrgica para Lograr Eficiencia y Seguridad).

INTRODUCTION: Neuromuscular blockade enables airway management, ventilation and surgical procedures. However there is no national consensus on its routine clinical use. The objective was to establish the degree of agreement among anaesthesiologists and general surgeons on the clinical use of neuromuscular blockade in order to make recommendations to improve its use during surgical procedures. METHODS: Multidisciplinary consensus study in Spain. Anaesthesiologists experts in neuromuscular blockade management (n=65) and general surgeons (n=36) were included. Delphi methodology was selected. A survey with 17 final questions developed by a dedicated scientific committee was designed. The experts answered the successive questions in two waves. The survey included questions on: type of surgery, type of patient, benefits/harm during and after surgery, impact of objective neuromuscular monitoring and use of reversal drugs, viability of a multidisciplinary and efficient approach to the whole surgical procedure, focussing on the level of neuromuscular blockade. RESULTS: Five recommendations were agreed: 1) deep neuromuscular blockade is very appropriate for abdominal surgery (degree of agreement 94.1%), 2) and in obese patients (76.2%); 3) deep neuromuscular blockade maintenance until end of surgery might be beneficial in terms of clinical aspects, such as as immobility or better surgical access (86.1 to 72.3%); 4) quantitative monitoring and reversal drugs availability is recommended (89.1%); finally 5) anaesthesiologists/surgeons joint protocols are recommended. CONCLUSIONS: Collaboration among anaesthesiologists and surgeons has enabled some general recommendations to be established on deep neuromuscular blockade use during abdominal surgery.

Pediatric Cardiac Intensive Care Society 2014 Consensus Statement: Pharmacotherapies in Cardiac Critical Care: Sedation, Analgesia and Muscle Relaxant.

OBJECTIVE: This article reviews pharmacotherapies currently available to manage sedation, analgesia, and neuromuscular blockade for pediatric cardiac critical patients. DATA SOURCES: The knowledge base of an expert panel of pharmacists, cardiac anesthesiologists, and a cardiac critical care physician involved in the care of pediatric cardiac critical patients was combined with a comprehensive search of the medical literature to generate the data source. STUDY SELECTION: The panel examined all studies relevant to management of sedation, analgesia, and neuromuscular blockade in pediatric cardiac critical patients. DATA EXTRACTION: Each member of the panel was assigned a specific subset of the studies relevant to their particular area of expertise (pharmacokinetics, pharmacodynamics, and clinical care) to review and analyze. DATA SYNTHESIS: The panel members each crafted a comprehensive summary of the literature relevant to their area of expertise. The panel, as a whole, then collaborated to cohesively summarize all the available, relevant literature. CONCLUSIONS: In the cardiac ICU, management of the cardiac patient requires an individualized sedative and analgesic strategy that maintains hemodynamic stability. Multiple pharmacological therapies exist to achieve these goals and should be selected based on the patient's underlying physiology, hemodynamic vulnerabilities, desired level of sedation and analgesia, and the projected short- or long-term recovery trajectory.

Limited professional guidance and literature are available to guide the safe use of neuromuscular block in infants.

AIM: Neuromuscular blocking agents (NMBAs) are used in a range of critical illnesses in neonates and infants, despite a lack of guidelines and professional standards. This study reviewed the current evidence base and ascertained UK practice regarding the continuous use of these agents in this age range. METHODS: We reviewed the literature and carried out a telephone questionnaire of all tertiary units in England and specialist children's hospital neonatal units in the UK. RESULTS: No best practice guidelines or general consensus statements were found, and the only randomised trial to feature an NMBA protocol expressed concerns about its use in such young babies. Of the 56 units contacted, 54 (96.4%) shared information. Only three of the 56 (5.4%) used intermittent boluses of NMBAs, 91.1% used NMBA infusions, 11 (19.6%) routinely used regular neuromuscular blocker pause to assess depth, and only one (1.8%) used peripheral nerve stimulation monitoring. All the units carried out clinical assessments, but only one (1.8%) had a written protocol. CONCLUSION: There is a paucity of literature and professional standards to guide the safe use of NMBAs in infants. Of the 54 units who participated in the survey, only one had a protocol for using NMBAs in babies.

[Moroccan survey about neuromuscular relaxant blocking drugs use and reversal management]. / Enquête sur les modalités de la curarisation et la décurarisation au Maroc.

OBJECTIVE: To determine current clinical neuromuscular use in Morocco anesthetic practice. STUDY DESIGN: Clinical practice survey. METHODS: Anesthesiologists were invited to answer anonymously to question about neuromuscular blocking agents (NMBA): pharmacology, monitoring and antagonism drug use. Corrected yates test was used to compare qualitative parameters and variance analysis for quantitative parameters. P<0.05 was considered as significant. RESULTS: We had 171 answers, 54% were paramedics (n=93) and 46% (n=78) were physicians (20% global effective in Morocco). Fifty-five percent were seniors. Vecuronium was the most NMBA used in Morocco for 51% of the anesthesiologists. Mean action time of NMBA was underestimate in more than 60% of the staff questioned specially for seniors (24.6%) than juniors (19.2%). Residual neuromuscular blockade was evaluated only by clinical and spirometric parameters in 72%. TOF monitor was used in 18% more in military hospitals (36%) and insurance clinics (40%) than private hospitals (12.5%). Administration of reversal drugs was systematic in 5.8% of anesthesiologists, frequent for 36.3% and rare for 55%. CONCLUSIONS: This study show an underestimation of residual neuromuscular blockade, poor neuromuscular monitor use and lack of knowledge of NMBA specially for senior anesthesiologists and in private hospitals. We should elaborate Moroccan guideline for NMBA use and provide formal training programs for our anesthetic staff.

El bloqueo neuromuscular residual como factor de riesgo para eventos críticos respiratorios en la Unidad de Recuperación Postanestésica / Residual neuromuscular block as a risk factor for critical respiratory events in the post anesthesia care unit

Objetivo. El bloqueo neuromuscular residual es una importante complicación postoperatoria asociada al uso de fármacos bloqueantes neuromusculares. El objetivo de este estudio fue valorar la incidencia de bloqueo neuromuscular residual en una unidad de recuperación postanestésica (URPA) y evaluar su asociación con eventos respiratorios críticos. Material y métodos. Estudio de cohortes, prospectivo realizado en una URPA durante un período de 3 semanas. Se incluyó a doscientos dos pacientes adultos sometidos a cirugía programada no cardiaca no-intracraneal. La variable de resultado principal fue la presencia de bloqueo neuromuscular residual después del ingreso en unidad de recuperación postanestésica definido como un cociente del tren de cuatro estímulos-TOFr<0,9 y objetivamente cuantificado usando aceleromiografía. Se registraron datos demográficos, variables perioperatorias, tiempo de permanencia en la unidad, tiempo de estancia hospitalaria y complicaciones respiratorias. La recuperación inadecuada se clasificó de acuerdo con la escala de agitación y sedación de Richmond 10 minutos después del ingreso en la unidad. Resultados. La incidencia de bloqueo neuromuscular residual en la URPA fue de 29,7% (Intervalo de Confianza 95%: 23,4 - 36,1). Los pacientes con bloqueo residual tuvieron eventos respiratorios críticos, considerados de forma global con mayor frecuencia (51% frente 16%, p<0,001), obstrucción de vía aérea (10% frente 2%, p=0,029), hipoxemia leve-moderada (23% frente 4%, p<0,001), hipoxemia grave (7% frente 1%, p=0,033), insuficiencia respiratoria(8% frente 1%, p=0,031), incapacidad para respirar profundamente (38% frente 12%, p<0,01) y debilidad muscular (16% frente 1%, p<0,001). El bloqueo neuromuscular residual fue más frecuente después de cirugía de alto riesgo (53% frente 33%, p=0,011) y se asociaba más a menudo con recuperación anestésica hipoactiva según lo definido por la escala de agitación y sedación de Richmond (21% frente 6%, p=0,001). Conclusiones. Este estudio sugiere que el bloqueo neuromuscular residual es común en la URPA y se asocia a mayor frecuencia de incidentes respiratorios críticos(AU)

Objective. Residual neuromuscular block is an important postoperative complication associated to the use of neuromuscular blocking drugs. The purpose of this study was to access the incidence of residual neuromuscular block in a post-anesthesia care unit and to evaluate its association with critical respiratory events. Material and methods. Prospective cohort study was conducted in a Post Anesthetic Care Unit (PACU) for a period of 3 weeks. Two hundred two adult patients who submitted to scheduled non-cardiac and non-intracranial surgery were eligible to the study. The primary outcome variable was residual neuromuscular block after arrival to PACU that was defined as train-of-four ratio <0.9 and objectively quantified using acceleromyography. Demographic data, perioperative variables, lengths of hospital and recovery room stay and critical respiratory events were recorded. Inadequate emergence was classified in its different forms according to the Richmond agitation and sedation scale 10min after admission to the recovery room. Results. Residual neuromuscular block incidence in the post-anesthesia care unit was 29.7% (95% confidence interval: 23.4, 36.1). Patients with residual neuromuscular block had more frequently overall critical respiratory events (51% versus 16%, P<0.001), airway obstruction (10% versus 2%, P=0.029), mild-moderate hypoxemia (23% versus 4%, P<0.001), severe hypoxemia (7% versus 1%, P=0.033), respiratory failure (8% versus 1%, P=0.031), inability to breathe deeply (38% versus 12%, P<0.001) and muscular weakness (16% versus 1%, P<0.001). Residual neuromuscular block was more common after high-risk surgery (53% versus 33%, P=0.011) and was more often associated with post-operative hypoactive emergence as defined by the Richmond Agitation and Sedation Scale (21% versus 6%, P=0.001). Conclusions. This study suggests that residual neuromuscular block is common in the PACU and is associated with more frequent critical respiratory events(AU)

Comentarios al artículo editorial «Managing perioperative neuromuscular block. Facial muscle monitoring may lead to faulty clinical decisions» / Comments on the editorial article "Managing perioperative neuromuscular block. Facial muscle monitoring may lead to faulty clinical decisions"

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Early and late parameters describing the offset of neuromuscular blockade are highly intercorrelated.

BACKGROUND: Neuromuscular blocking agents have always shown wide inter-individual variability when it comes to their duration of action. This prevents clinicians from anticipating the evolution of the neuromuscular block for any given patient. With this study, we aimed to assess the nature of the relationships existing between different time course parameters used to describe paralysis onset and offset. METHODS: Sixty American Society of Anesthesiologists (ASA) score III-IV anaesthetised patients were randomised to receive a single equipotent dose (2ED95) of either rocuronium, mivacurium or atracurium. We used acceleromyography to monitor neuromuscular transmission. We described the relationships between the time-interval measurements of: onset, the first response (T1) reappearance, T1 25% of control, train-of-four ratio 0.25 and 0.75. Pearson correlation coefficients were calculated. RESULTS: We found no significant relationships between onset and any of the four parameters used to describe the offset. On the other hand, we showed strong and highly significant linear relationships between all the parameters describing the offset for each of the muscle relaxants studied (correlation coefficients ranging from 0.850 to 0.992). CONCLUSIONS: We evidenced strong linear correlations between the four offset time course parameters of spontaneous recovery after a single neuromuscular blocking agents (NMBAs) bolus. Such relationships open up new clinical perspectives concerning quantitative neuromuscular transmission monitoring: the scope of individual valuable anticipation of the patient's recovery.

Laboratory guidelines for animal care.

Animal research is a controversial subject because of the ethical and moral implications of using unwilling research subjects in potentially painful or distressful procedures usually ending in euthanasia. As such, it must be conducted in a compassionate and responsible manner geared toward maximizing the animals' quality of life prior to and during experimentation. Because of its contentious nature, the conduct of animal research is highly regulated at the federal, state, city, and institutional levels. It is essential that researchers acquire a working knowledge of the procedures and regulations in order to protect themselves and their staff from occupational hazards as well as protect their labs from criticism or attack from animal rights organizations. Perhaps the best way to protect from the latter is to avoid inadvertent instances of noncompliance with their research protocol or applicable regulations. Regulatory noncompliance can also have serious negative consequences on investigators' research ranging from temporary suspension of their protocols to loss of funding or principal investigator status. To minimize such events, it is advised that researchers build positive and collaborative relationships, trust and rapport with key institutional players, such as the veterinary staff, the Institutional Animal Care and Use Committee (IACUC), and top administrators. Guidance is provided regarding the appropriate handling of regulatory noncompliances.