Evaluation of Rocuronium Continuous Infusion in Critically Ill Patients During the COVID-19 Pandemic and Drug Shortages.

Background: Limited data exist to support the use of rocuronium continuous infusions in the intensive care unit (ICU). Objective: To evaluate the dosing and monitoring of adult patients who received rocuronium for hypoxemic respiratory failure during the Coronavirus Disease 2019 (COVID-19) pandemic. Methods: This was a retrospective, single-center study from March 1, 2020 to May 31, 2020. We identified all adult patients admitted to any ICU who received rocuronium via continuous infusion. Patients were excluded if they received rocuronium for <6 hours. The main outcome of this study was to determine the median rocuronium maintenance continuous infusion rate in the ICU. Secondary outcomes of this study included the initial continuous infusion rate, duration of therapy, cumulative dose, frequency and median of rocuronium boluses, time to resolution of neuromuscular blockade, and the relationship between the hourly administration rates of rocuronium and train-of-four (TOF) assessments. Results: Seventy-one patients and 97 paralytic infusions were included. Fifty-nine patients (83%) were positive for SARS CoV-2. Of the 97 rocuronium infusions, the median dose at initiation was 3 (3-5) mcg/kg/min and duration of infusion was 45 (23.6-92.5) hours. The median continuous infusion maintenance rate was 4.3 (2.8-7.2) mcg/kg/min. There was a negligible correlation between the dose of rocuronium and the TOF results (r = .04). A total of 1775 TOFs were assessed, of which 46.2% were over-paralyzed, 35.7% well-paralyzed, and 18.1% under-paralyzed. Conclusions: The initial and maintenance infusion doses in our analysis were lower than what have been previously referenced.

Molecular mechanisms of muscular and non-muscular actions of neuromuscular blocking agents in critical illness.

Despite frequent use of neuromuscular blocking agents in critical illness, changes in neuromuscular transmission with critical illness are not well appreciated. Recent studies have provided greater insights into the molecular mechanisms for beneficial muscular effects and non-muscular anti-inflammatory properties of neuromuscular blocking agents. This review summarises the normal structure and function of the neuromuscular junction and its transformation to a 'denervation-like' state in critical illness, the underlying cause of aberrant neuromuscular blocking agent pharmacology. We also address the important favourable and adverse consequences and molecular bases for these consequences during neuromuscular blocking agent use in critical illness. This review, therefore, provides an enhanced understanding of clinical therapeutic effects and novel pathways for the salutary and aberrant effects of neuromuscular blocking agents when used during acquired pathologic states of critical illness.

NEUROMUSCULAR BLOCKING AGENT BUNDLES IN THE MEDICAL ICU TO PREVENT PROLONGED USE OF PARALYTICS IN PATIENTS WITH COVID-19-RELATED ARDS

SESSION TITLE: ECMO and ARDS in COVID-19 Infections SESSION TYPE: Rapid Fire Original Inv PRESENTED ON: 10/17/2022 12:15 pm - 1:15 pm PURPOSE: The use of neuromuscular blocking agents (NMBA) has been trialed in acute respiratory distress syndrome (ARDS) to decrease patient–ventilator desynchrony, decrease work of breathing and improve oxygenation. No consistent reduction in mortality or ventilator free days has been demonstrated. The use of NMBA’s can be associated with neuromuscular weakness and adverse cardiovascular events. The use of NMBA’s increased significantly in our ICU after the advent of COVID-19, partly related to the increase incidence of ARDS observed, but also because of the seemingly increased ventilator asynchrony seen in this patient population. Our group evaluated the use of NMBA infusions in our medical intensive care unit (MICU) and subsequently implemented a “Paralytic initiation decision bundle” to decrease the frequency (and duration) of NMBA infusions by optimizing conditions before initiating an NMBA. METHODS: We conducted a retrospective cohort evaluation of the pattern of NMBA usage in our MICU from December 2020 to May 2021 at the Memorial Hermann Hospital-Texas Medical Center. Patients were excluded if they were on ECMO or if the NMBA infusions were initiated at an outside hospital. We then started an NMBA initiation bundle to decrease the overuse of this intervention. RESULTS: Forty-four patients were initiated on an NMBA infusion during the preintervention period (average 7.3 patients/month). This cohort included 63% males, an average age of 59.7 years (SD +/- 13.3), with 81.8% diagnosed with COVID-19. 54.5% were started on a paralytic drip <24 hours after intubation, 11.4% between 24 and 48 hours and 34.1% were started on a paralytic drip >48 hours after intubation (mean 7.5 days;range of 3-15 days). 27 patients (61.4%) were noted to be on an NMBA infusion for greater than 48 hours. The average duration of continuous paralytic infusion in this group was 5.2 days (SD +/- 3.1;range of 3-16 days). After a paralytic bundle was implemented, the use of NMBAs dropped significantly (2 patients/month) with an average infusion duration of <48 hours. CONCLUSIONS: The use of NMBA’s for greater than 48 hours in patients with ARDS is not currently recommended. The extended use of paralytics is seen often in COVID-19 ARDS patients. The implementation of a paralytic bundle with alternatives for sedation, optimization of alternative ARDS treatment strategies and a mandatory stop (or reevaluation) of NMBA after 48 hours resulted in a reduction in paralytic use at our institution. Limitations of this study include the decrease in COVID-19 cases during the intervention (hence restricting the evaluation of the tool). We plan to continue to investigate the intervention and add to our current data. Further studies are also needed to investigate the optimal use of paralytics in COVID-19 ARDS. CLINICAL IMPLICATIONS: The use of an NMBA bundle in patient’s with ARDS can help reduce the overuse of this intervention. DISCLOSURES: No relevant relationships by Jennifer Cortes No relevant relationships by Kimberly DSouza No relevant relationships by Galyna Ivashchuk No relevant relationships by Ruckshanda Majid No relevant relationships by Zachary Pinchover No relevant relationships by Oriana Salamo

MALIGNANT HYPERTHERMIA AND COVID-19: IS THERE A CORRELATION?

SESSION TITLE: COVID-19 Case Report Posters 2 SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Malignant hyperthermia (MH) is a hypermetabolic crisis where an increase in carbon dioxide is seen despite an increased minute ventilation with a proposed mechanism as a disturbance in calcium homeostasis. Commonly seen in volatile anesthetic agents and depolarizing neuromuscular blockers, rarely with nondepolarizing agents. There has been one reported case of cisatracurium-induced MH in the setting of ARDS. There have been two cases reported of nondepolarizing neuromuscular agents causing MH in the setting of COVID-19. CASE PRESENTATION: A 34-year-old man with severe COVID-19 complicated by ARDS on ventilator day 16, due to refractory fevers, ventilatory dyssynchrony, high minute ventilation and auto-PEEP phenomena, the decision was made to attempt neuromuscular paralysis. After one dose of cisatracurium, the patient became hyperthermic and end-tidal carbon-dioxide increased from 58-98 with inability to oxygenate. The patient developed high peak pressures, bedside ultrasound revealed no evidence of pneumothorax also confirmed with chest x-ray. The patient then received a dose of dantrolene with end-tidal improving to 60 and tachycardia also resolved. A creatinine kinase level drawn was elevated at 571. DISCUSSION: A proposed mechanism of MH is calcium release from sarcoplasmic reticulum, a mutation in skeletal muscle ryanodine receptor calcium release channels that can release IL-6 when activated leading to excessive muscular contraction. Proinflammatory cytokine IL-6, dantrolene may block IL-6 release which results in its therapeutic effect in the treatment of MH. IL-6 has been used to predict deterioration from COVID-19. Dantrolene in this sense has been proposed as a potential therapeutic agent against COVID-19, inhibiting intracellular calcium influx thus preventing the pathological feedback of viral entry into cells via endocytosis, as this is a calcium dependent process. Given the possible link between IL-6 release, calcium and MH, SARS-CoV-2 viral entry into cells may place patients at higher risk of MH. Patients with COVID-19 may be at higher risk of MH, even in rare agents such as non-depolarizing agents as seen in this case. Awareness of this potentially increased complication from these agents in those patients with COVID-19 is key as we continue in the ongoing global pandemic. CONCLUSIONS: Given the possible link between IL-6 release, calcium and MH, SARS-CoV-2 viral entry into cells may place patients at higher risk of MH. Patients with COVID-19 may be at higher risk of malignant hyperthermia, even in rare agents such as non-depolarizing agents as seen in this case. Awareness of this potentially increased complication from these agents in those patients with COVID-19 is key as we continue in the ongoing global pandemic. Reference #1: Sathyanarayanan SP, Hamza M, Hamid K, Groskreutz D. Cisatracurium-Associated Malignant Hyperthermia During Severe Sars-CoV-2 Infection. Am J Ther. 2021 Aug 10;28(5):e590-e591. doi: 10.1097/MJT.0000000000001437. PMID: 34387563;PMCID: PMC8415506. Reference #2: Chiba N, Matsuzaki M, Mawatari T, Mizuochi M, Sakurai A, Kinoshita K. Beneficial effects of dantrolene in the treatment of rhabdomyolysis as a potential late complication associated with COVID-19: a case report. Eur J Med Res. 2021 Feb 8;26(1):18. doi: 10.1186/s40001-021-00489-8. PMID: 33557936;PMCID: PMC7868892. Reference #3: Han H, Ma Q, Li C, Liu R, Zhao L, Wang W, Zhang P, Liu X, Gao G, Liu F, Jiang Y, Cheng X, Zhu C, Xia Y. Profiling serum cytokines in COVID-19 patients reveals IL-6 and IL-10 are disease severity predictors. Emerg Microbes Infect. 2020 Dec;9(1):1123-1130. doi: 10.1080/22221751.2020.1770129. PMID: 32475230;PMCID: PMC7473317. DISCLOSURES: No relevant relationships by Hira Bakhtiar No relevant relationships by Timothy DAmico no disclosure on file for Sarah Margolskee;No relevant relationships by Carlos Merino No relevant relationships by Joanna Moore

Time taken to wake post sedation hold and the impact on functional performance at intensive care unit (ICU) discharge: Do COVID rehabilitation phenotypes exist?

Introduction: The COVID-19 pandemic caused a sudden and unprecedented surge in ICU admissions for severe acute respiratory failure. Whilst there is a wealth of knowledge surrounding risk factors for developing critical care myopathy and effects of prolonged ICU stay on functional outcomes,1,2 little was known about the pathophysiology, treatment or physical outcomes of patients admitted to ICU with COVID-19. In our organisation, patients recovering from the acute phase of COVID-19 demonstrated a range of presentations impacting rehabilitation whist in ICU. Objective: To explore whether time taken to wake post sedation hold impacts on functional outcomes of patients surviving ICU admission for COVID-19. Methods: A retrospective review of patients admitted to ICU with a primary diagnosis of COVID-19 between March-April 2020 was conducted at a large London NHS Foundation Trust. Electronic clinical notes were reviewed and the following data extracted: age, ethnicity, sex, BMI, pre-admission clinical frailty score, duration of sedation, days taken to wake from sedation, duration of mechanical ventilation (MV), ICU length of stay (LOS) and hospital LOS. Functional outcomes were defined using the Intensive Care Unit Mobility Score (ICUMS). Data were analysed using descriptive statistics, reported as absolute numbers, percentages (%) and median (range). Results: 203 patients were identified, 137 were excluded as 58 died, 3 were incidental findings of COVID-19, 67 had missing data due to paper notes or transfers in/out of the Trust and 9 were duplicate records. Sixty-six patients were included in the final analysis (Table 1). Patients could be categorised into four rehabilitation groups: 1 = Never requiring sedation and MV, 2 = Woke from sedation (defined as RASS ≥-1) within 72 hours with preserved muscle power (defined as ICUMS ≥5 on ICU discharge), 3 = Woke from sedation within 72 hours but myopathic (defined as ICUMS ≤4 on ICU discharge), 4 = Slow to wake (> 72 hrs). Those slow to wake following sedation hold (group 4) had an increased age, BMI, and higher proportion of nonwhite ethnicity. Neuromuscular blocking agents (NMBA) and steroid use was more prevalent in group 4 compared to the other groups. There was also increased midazolam administration and higher number of total sedative agents received by these patients. Those slow to wake had a lower ICUMS at ICU discharge than those waking with preserved strength or never sedated (3, 6, 9 respectively). Those who were slow to wake were ventilated for longer than the other groups. Time taken to wake from sedation also resulted in longer ICU and hospital LOS. Similar functional outcomes at hospital discharge were noted between all 4 groups (Table 1). Conclusion: Patients slow to wake from sedation following ICU admission for a primary diagnosis of COVID-19 had a longer ICU LOS, reduced functional ability at ICU discharge and a longer hospital LOS. These preliminary observational clinical data support the testable hypothesis that within in the ICU, COVID rehabilitation phenotypes may exist which warrants further investigation.

Difficult and failed intubation management in obstetrics

Failed intubation in obstetrics remains a topical issue, a rare but potentially devastating complication of obstetric general anaesthesia. The 2015 guidelines produced following several years of collaborative work between the Difficult Airway Society (DAS) and Obstetric Anaesthetists' Association (OAA) remain the definitive text. While deaths from failed intubation have declined significantly over 30 years, the incidence of failed intubation remains fairly constant at 1:300, with the latest studies showing a rate of 1:224. This reflects the significant decline in the use of general anaesthesia for caesarean section over the last three decades;however, it also highlights a decreased exposure for trainees to tracheal intubation in the obstetric population.

Early short course of neuromuscular blocking agents in patients with COVID-19 ARDS: a propensity score analysis.

BACKGROUND: The role of neuromuscular blocking agents (NMBAs) in coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS) is not fully elucidated. Therefore, we aimed to investigate in COVID-19 patients with moderate-to-severe ARDS the impact of early use of NMBAs on 90-day mortality, through propensity score (PS) matching analysis. METHODS: We analyzed a convenience sample of patients with COVID-19 and moderate-to-severe ARDS, admitted to 244 intensive care units within the COVID-19 Critical Care Consortium, from February 1, 2020, through October 31, 2021. Patients undergoing at least 2 days and up to 3 consecutive days of NMBAs (NMBA treatment), within 48 h from commencement of IMV were compared with subjects who did not receive NMBAs or only upon commencement of IMV (control). The primary objective in the PS-matched cohort was comparison between groups in 90-day in-hospital mortality, assessed through Cox proportional hazard modeling. Secondary objectives were comparisons in the numbers of ventilator-free days (VFD) between day 1 and day 28 and between day 1 and 90 through competing risk regression. RESULTS: Data from 1953 patients were included. After propensity score matching, 210 cases from each group were well matched. In the PS-matched cohort, mean (± SD) age was 60.3 ± 13.2 years and 296 (70.5%) were male and the most common comorbidities were hypertension (56.9%), obesity (41.1%), and diabetes (30.0%). The unadjusted hazard ratio (HR) for death at 90 days in the NMBA treatment vs control group was 1.12 (95% CI 0.79, 1.59, p = 0.534). After adjustment for smoking habit and critical therapeutic covariates, the HR was 1.07 (95% CI 0.72, 1.61, p = 0.729). At 28 days, VFD were 16 (IQR 0-25) and 25 (IQR 7-26) in the NMBA treatment and control groups, respectively (sub-hazard ratio 0.82, 95% CI 0.67, 1.00, p = 0.055). At 90 days, VFD were 77 (IQR 0-87) and 87 (IQR 0-88) (sub-hazard ratio 0.86 (95% CI 0.69, 1.07; p = 0.177). CONCLUSIONS: In patients with COVID-19 and moderate-to-severe ARDS, short course of NMBA treatment, applied early, did not significantly improve 90-day mortality and VFD. In the absence of definitive data from clinical trials, NMBAs should be indicated cautiously in this setting.

Excess oxygen administration and adverse outcomes in patients with SARS-CoV-2 pneumonia requiring invasive mechanical ventilation: a retrospective study

Introduction: Even if life-saving in most cases, excess O2 may have adverse effects. We described the prevalence of hyperoxemia and excess O2 administration in patients with severe acute respiratory syndrome due to novel coronavirus (SARS-CoV-2) and explored the association with mortality in the intensive care unit (ICU) or ventilatorassociated pneumonia (VAP). Methods: Retrospective single-centre study on 134 patients with SARS-CoV-2 requiring mechanical ventilation for ≥ 48 h. We calculated the excess O2 administered based on an ideal arterial O2 tension ( PaO2) target of 55-80 mmHg. We defined hyperoxemia as PaO2 > 100 mmHg and hyperoxia + hyperoxemia as an inspired O2 fraction (FiO2) > 60% + PaO2 > 100 mmHg. Risk factors for ICU-mortality and VAP were assessed with multivariate analyses. Results: Each patient received an excess O2 of 1121 [829-1449] l per day of mechanical ventilation. Hyperoxemia was found in 38 [27-55] % of arterial blood gases, hyperoxia + hyperoxemia in 11 [5-18] %. The FiO2 was not reduced in 69 [62-76] % of cases of hyperoxemia. Adjustments were more frequent with higher PaO2 or initial FiO2 levels. ICU-mortality was 32%. VAP was diagnosed in 48.5% of patients. Hyperoxemia (odds ratio [OR] 1.300 95% confidence interval [1.097- 1.542]) and hyperoxia + hyperoxemia (OR 1.144 [1.008-1.298]) were associated with higher risk for ICU-mortality, independently of age, Sequential Organ failure Assessment score at ICU-admission and mean PaO2/FiO2. Hyperoxemia (OR 1.033 [1.006-1.061]), hyperoxia + hyperoxemia (OR 1.038 [1.003-1.075]) and daily excess O2 (OR 1.001 [1.000- 1.001]) were identified as risk factors for VAP, independently of body mass index, blood transfusions, days of neuromuscular blocking agents before VAP, prolonged prone positioning and mean PaO2/FiO2 before VAP. Conclusions: Excess O2 administration and hyperoxemia were common in mechanically ventilated patients with SARS-CoV-2 and may be associated with ICU-mortality and greater risk for VAP.

COVID-19 Pharmacotherapy Was Not Associated with Mortality in a Community Teaching System

Background. During the COVID-19 pandemic, a task force was assembled to collect data on patient characteristics and treatment exposures to assess what factors may contribute to patient outcomes, and to help develop institutional treatment guidelines. Methods. A retrospective study was performed on COVID-19 inpatient admissions within a four-hospital community health system over a six-month period from April-October 2020. Positive COVID-19 immunology results and/in conjunction with an inpatient admission was criteria for inclusion. Covariates for age, gender, race were added apriori. Covariates of interest included baseline comorbidities, admission levelof-care, vital signs, mortality outcomes, need for intubation, and specific pharmacological treatment exposures. Logistic regression was performed on our final model and reported as OR +/- 95% CI. Results. A total of 349 patients met inclusion criteria. Pharmacotherapies were not associated with a difference in mortality in a four-hospital system. Corticosteroids (p = 0.99);Remdesivir (p = 0.79);hyrdroxychloroquine (p = 0.32);tocilizumab (p = 0.91);were not associated with mortality. ACE-inhibitor or angiotensin II receptor blockers OR 0.29 (0.09-0.93) (p = 0.03);convalescent plasma OR 7.85 (1.47-42.1) (p = 0.02);neuromuscular blocking agents (NMBA) OR 5.51 (1.28-23.8) (p = 0.02);vasopressors OR 17.6 (5.62-54.9) (p = 0.00) were associated with in-hospital mortality. Covariates that were associated with a difference in mortality were: age > 60 years OR 2.73 (1.04-7.14) (p = 0.04);structural lung disease OR 3.02 (1.28-7.10) (p = 0.01). Covariates not associated with mortality included African American race (p = 0.30);critical care admission (p = 0.19);obesity (p = 0.06);cardiovascular disease (p = 0.89);diabetes (p = 0.28). Conclusion. The use of corticosteroids, remdesivir, tocilizumab, and hydroxychloroquine, and admission to a critical care bed was not associated with a difference of in-hospital mortality. Patients who required vasopressors or NMBA were associated with in-hospital mortality. Despite national trends reporting increased mortality in patients with obesity, diabetes, cardiovascular disease, and of African American race, this was not observed in our health system safety net hospitals.

Physicians' attitudes and perceptions of neuromuscular blocker infusions in ARDS

INTRODUCTION: With the COVID pandemic, and recently updated practice guidelines for neuromuscular infusion (NMBI) use during ARDS, the practices/perceptions of ICU physicians regarding NMBI use during ARDS may not be evidence-based. METHODS: We developed, tested, and electronicallyadministered a questionnaire (9 questions/70 subquestions) to medical and surgical ICU fellow and attending physicians at 3 geographically-diverse U.S. health systems (U Arizona, U Chicago, Mass General Brigham). The IRB-approved questionnaire focused on adults with moderate-severe ARDS (PaO2:FiO2 < 150) with critical hypoxemia where dyssynchrony causes were addressed and PEEP optimized. Weekly reminders were sent twice. RESULTS: Respondents [173/342(50.5%)] primarily worked as an attending 117(75%) in a medical ICU 94(60%) for 12±8 weeks/year. COVID+ ARDS patients were twice as likely to receive a NMBI (56±37 vs. 28±19%;p< 0.01). Respondents somewhat/strongly agreed a NMBI: should be reserved until after a trial of deep sedation 142 (82%) or proning 59 (34%), be dose-titrated based on trainof- four monitoring 107(62%);and effectively reduced dyssynchrony 149(86%), plateau pressure 106(62%) and barotrauma 102(60%). Few respondents [23(18%)] somewhat/strongly agreed a NMBI should be initiated at ARDS onset 20(12%) or administered at a fixed-dose 12(7%). Only 2/14 potential NMBI risks were frequently reported to be of high/very high concern: prolonged muscle weakness during steroids 135(79%) and paralysis awareness due to inadequate sedation 114(67%). Only absence of dyssynchrony 146(87%) was frequently reported to be a very/extremely important NMBI titration target. Train-of-four 78(46%) and BIS 39(23%) monitoring and plateau pressure 67(40%) or PaO2:FiO2 64(38%) evaluation were deemed less important. Absence of dysschrony 93(56%) and use ≥48 hours 87(53%) were preferred NMBI stopping criteria. For COVID+ patients, few felt reduced self-extubation and COVID aerosolization during reintubation 16(9%) or reduced ventilator adjustments 7(5%) were very/extremely important reasons for NMBI use. CONCLUSIONS: Most physicians agree NMBI infusions in ARDS should be reserved until after trials of deep sedation. Paralysis awareness and prolonged muscle weakness are the greatest NMBI use concerns. Unique considerations in COVID+ ARDS patients exist.

Evaluation of sedation and analgesia with the use of neuromuscular blocking agents

INTRODUCTION: During the COVID-19 pandemic, continuous infusion neuromuscular blocking agents (NMBA) were frequently utilized. International guidelines for NMBA use in critically ill patients recommend patients achieve deep sedation using a continuous sedative and analgesic prior to and during neuromuscular blockade, and documentation is essential to confirm adequate sedation. The aim of this evaluation was to assess the use of sedation and analgesia in paralyzed patients. METHODS: A retrospective multi-center study was performed on fifty adult patients randomly selected from five hospitals across the health system based on the proportion of patients on NMBA at each delivery network. Patients were included if they received a continuous infusion NMBA between March 24 and May 8, 2020. The primary outcome was documentation of adequate sedation and analgesia prior to NMBA initiation, defined as a Richmond Agitation- Sedation Scale (RASS) -4 to -5 while receiving both sedative and analgesic infusions. Secondary outcomes included RASS documentation within 2 hours prior to and bispectral index (BIS) 2 hours after NMBA initiation, and incidence of medication orders updated with appropriate sedation goal. RESULTS: We identified 21 (42%) patients with documentation of adequate sedation and analgesia prior to NMBA initiation. Adequate sedation was documented in 22 (44%) patients, with 24 (48%) not at goal, 3 (6%) not documented, and 1 (2%) without a continuous sedative order. Adequate analgesia was documented in 39 (78%) patients, with 8 (16%) having as-needed intravenous (IV) push opiates orders and 3 (6%) without analgesia orders. Medication orders were updated with appropriate sedation goal in 2 (4%) patients. Documentation of sedation was completed within 2 hours of NMBA initiation in 25 (50%) patients and in 18 (36%) 2 hours after initiation. CONCLUSIONS: Electronic health records should be optimized to facilitate ordering appropriate sedation and analgesia with appropriate titration parameters, and to ensure that an appropriate level of sedation is documented prior to NMBA initiation. Adequate documentation may have been limited due to BIS monitor availability and medication orders with outdated titration parameters.