Intraoperative Versus Postoperative Hydroxocobalamin for Vasoplegic Shock in Cardiothoracic Surgery.

OBJECTIVES: Hydroxocobalamin inhibits nitric oxide pathways contributing to vasoplegic shock in patients undergoing cardiopulmonary bypass (CPB). The objective of this study was to evaluate the effect of intraoperative versus postoperative application of hydroxocobalamin for vasoplegic shock in patients undergoing CPB. DESIGN: This was a historic cohort study. SETTING: The study was conducted at a quaternary academic cardiovascular surgery program. PARTICIPANTS: Adults undergoing cardiac surgery using CPB were participants in the study. INTERVENTIONS: Hydroxocobalamin (5 g) intravenously over 15 minutes. MEASUREMENTS AND MAIN RESULTS: The treatment groups were assigned based on the receipt location of hydroxocobalamin (ie, intensive care unit [ICU] versus operating room [OR]). The primary outcome was vasopressor-free days in the first 14 days after CPB. Of the 112 patients included, 37 patients received hydroxocobalamin in the OR and 75 in the ICU. Patients in the OR group were younger than those in the ICU group (57.5 v 63.9 years, p = 0.007), with statistically similar American Society of Anesthesiologists scores. The mean CPB duration was 3.4 hours in the OR group and 2.9 hours in the ICU group (p = 0.09). In both groups, the norepinephrine-equivalent dose of vasopressors at hydroxocobalamin was 0.27 µg/kg/min. Days alive and free of vasopressors were not different between the OR and ICU groups (estimated difference 0.48 [95% CI -1.76-2.72], p = 0.67). The odds of postoperative renal failure, mesenteric ischemia, ICU, hospital length of stay, and in-hospital mortality were also similar between groups. CONCLUSIONS: A difference in vasopressor-free days after CPB was not found between patients who received hydroxocobalamin intraoperatively versus postoperatively for vasoplegic shock.

Hydroxocobalamin for Vasodilatory Hypotension in Shock: A Systematic Review With Meta-Analysis for Comparison to Methylene Blue.

Hydroxocobalamin inhibits nitric oxide-mediated vasodilation, and has been used in settings of refractory shock. However, its effectiveness and role in treating hypotension remain unclear. The authors systematically searched Ovid Medline, Embase, EBM Reviews, Scopus, and Web of Science Core Collection for clinical studies reporting on adult persons who received hydroxocobalamin for vasodilatory shock. A meta-analysis was performed with random-effects models comparing the hemodynamic effects of hydroxocobalamin to methylene blue. The Risk of Bias in Nonrandomized Studies of Interventions tool was used to assess the risk of bias. A total of 24 studies were identified and comprised mainly of case reports (n = 12), case series (n = 9), and 3 cohort studies. Hydroxocobalamin was applied mainly for cardiac surgery vasoplegia, but also was reported in the settings of liver transplantation, septic shock, drug-induced hypotension, and noncardiac postoperative vasoplegia. In the pooled analysis, hydroxocobalamin was associated with a higher mean arterial pressure (MAP) at 1 hour than methylene blue (mean difference 7.80, 95% CI 2.63-12.98). There were no significant differences in change in MAP (mean difference -4.57, 95% CI -16.05 to 6.91) or vasopressor dosage (mean difference -0.03, 95% CI -0.12 to 0.06) at 1 hour compared to baseline between hydroxocobalamin and methylene blue. Mortality was also similar (odds ratio 0.92, 95% CI 0.42-2.03). The evidence supporting the use of hydroxocobalamin for shock is limited to anecdotal reports and a few cohort studies. Hydroxocobalamin appears to positively affect hemodynamics in shock, albeit similar to methylene blue.

Buffered Lidocaine as an Endotracheal Tube Cuff Media In Immediate Postoperative Cardiac Surgery Patients And Its Effect On Sedation Requirements: A Prospective Feasibility Study.

Tracheal mucosal inflammation and irritation caused by the endotracheal tube (ETT) may exacerbate symptoms of pain and discomfort which create challenges including ETT tolerance and postintubation emergence phenomena. Various sedative and analgesic agents are used to mitigate these symptoms, however, there is concern that such medications may contribute to prolonged duration of intubation, length of intensive care unit (ICU) stay, as well as increased morbidity. This randomized control pilot study explored the feasibility and potential efficacy of instillation of a buffered lidocaine solution as an ETT cuff medium in adult rapid recovery eligible cardiac surgical patients. Thirty-two patients were randomized to the intervention (1.8% lidocaine/0.76% sodium bicarbonate) or control (air) group. Data were analyzed using median, standard deviation (SD), Wilcoxon rank sum, mean ± SD, two-sample t-test, and Fisher's exact test. The intervention arm demonstrated a trend toward a reduction in the incidence of cough at ICU arrival (0 versus 22%), incidence of pharyngitis at all time intervals, and propofol requirement (345 ± 248 mg versus 1,158 ± 1,426 mg) with no difference in adverse events between groups. These results support the development of larger studies to confirm the efficacy and feasibility of buffered lidocaine as an ETT cuff medium in this population.

Predicting the Response of Hydroxocobalamin in Postoperative Vasoplegia in Recipients of Cardiopulmonary Bypass.

OBJECTIVE: The primary aim of this study was to identify predictors of response to hydroxocobalamin. DESIGN: A retrospective cohort study. SETTING: A single large academic medical center within the cardiovascular surgery intensive care unit. PARTICIPANTS: Postoperative cardiovascular surgery patients within 96 hours of cardiopulmonary bypass separation between May 7, 2018, and August 1, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 66 administrations, 43 administrations yielded hemodynamic improvements (65.2%). Comparing responders to nonresponders, nonresponders had a greater median cardiopulmonary bypass duration (223 v 131 minutes; p < 0.001) and a prolonged median cross-clamp time (153 v 77 minutes; p = 0.014). Multivariate modeling demonstrated a reduction in the odds of being a responder by 57% for every 60 minutes of cardiopulmonary bypass duration (odds ratio, 0.43; 95% confidence interval, 0.28-0.68; p < 0.001), but there was no significant difference based on time from intensive care unit admission to hydroxocobalamin administration (odds ratio, 0.95; 95% confidence interval, 0.88-1.03; p = 0.20). CONCLUSION: Shorter total bypass duration and more rapid utilization after bypass of hydroxocobalamin were associated with a higher likelihood of response to refractory vasoplegic shock.

General Anesthesia With and Without Remifentanil for Flexible and Rigid Bronchoscopy: A Retrospective Case-Matched Study.

Prior research suggests general anesthesia (GA) with remifentanil is superior to GA without remifentanil regarding perioperative outcomes, including the postanesthesia care unit (PACU) length of stay (LOS). The objective of this study was to compare the intraoperative management and PACU LOS in patients who underwent GA with or without remifentanil for bronchoscopy. The study included 5,763 adult patients who underwent flexible bronchoscopy and received GA with or without remifentanil or who underwent rigid bronchoscopy and received GA with or without remifentanil. Despite prolonged procedural length in both the flexible and rigid bronchoscopy groups and greater ASA score in the flexible bronchoscopy group, no difference in the adjusted PACU LOS or time to extubation was found. Remifentanil was associated with hemodynamic perturbations and desaturation events. Remifentanil was associated with a significant reduction in nonremifentanil opioid requirements. Although both groups receiving remifentanil were associated with a less favorable intraoperative hemodynamic profile, remifentanil did not increase the incidence of postoperative complications despite that group having a greater ASA score and procedural duration.

Outcomes of adult patients supported by extracorporeal membrane oxygenation (ECMO) following cardiopulmonary arrest. The Mayo Clinic experience.

INTRODUCTION: To describe our experience in use of extracorporeal life support (ECLS) as a rescue strategy in patients following cardiopulmonary resuscitation. METHODS: A retrospective analysis was performed for patients (n = 101) who received ECLS after cardiorespiratory arrest between May 2001 and December 2014. The primary outcome was survival to hospital discharge. RESULTS: In this cohort median (IQR) age was 56 (37-67) years, 53 (53%) were male, and 90 (89%) were Caucasian. Ventricular tachycardia or ventricular fibrillations were the initial cardiac rhythm in 49 (48.5%) and asystole/pulseless electrical activity in 37 (36.8%). Median (IQR) time to initiation of extracorporeal support from arrest time was 72 (43-170) min. The median (IQR) duration of support was 100 (47-157) hours. Renal failure (66%) and bleeding (66%) were the two most commonly observed complications during ECLS support. The survival to hospital discharge was seen in 47 (47%) patients, and good neurologic outcome (mRs 0-3) was seen in 29%. Acidosis, lactate and continuous renal replacement therapy were independent predictors of mortality. The median (IQR) intensive care unit stay was 14 (4-28) days and hospital stay was 17 (4-35) days. CONCLUSION: Our institutional experience with ECLS as a rescue measure following cardiac arrest is associated with improvement in mortality, and favorable neurologic status at hospital discharge.

Extended Duration Infusion of Hydroxocobalamin for Vasoplegic Rescue in Septic Shock.

Nitric oxide (NO) is a gaseous signaling molecule and a key endogenous mediator of vascular tone. Hydroxocobalamin (HCB) affects NO-mediated vasoplegia as (1) a direct inhibitor of nitric oxide synthase (NOS), thereby decreasing its production, and (2) by binding directly to NO and acting as a scavenger. HCB has been increasingly used in the treatment of refractory vasoplegia, particularly in cardiac surgery and liver transplant patients. Sepsis and septic shock are characterized by an increase in inducible NOS expression and activity with excessive NO production, resulting in endothelial dysfunction and profound systemic vasodilation. Therefore, a careful sustained reduction in NO burden represents a potential therapeutic target. Here, we present a case of refractory septic shock, which resolved after an extended duration infusion of high-dose HCB. We hope to foster further exploration regarding the safety, dosing, and efficacy of HCB when administered for vasopressor refractory septic shock.

Description of Pharmacogenomic Testing Among Patients Admitted to the Intensive Care Unit After Cardiovascular Surgery.

BACKGROUND: Pharmacogenomic (PGx) testing has the potential to provide information on specific drug-metabolizing enzymes that may lead to an absence, reduction, or increase in medication effect in patients. There is a paucity of prospective studies examining PGx testing in the intensive care unit (ICU) setting. RESEARCH AIMS: To (1) obtain a PGx panel in a sample of cardiovascular (CV) surgical patients with a planned ICU stay and identify phenotypes, and (2) identify PGx variants that may inform treatment regimens and may warrant prescribing adjustments. DESIGN AND METHODS: Descriptive, single cohort cross-sectional design. Adult (≥18 years) CV patients with an anticipated postoperative ICU stay were enrolled from a large Midwestern tertiary academic medical center. Eligible patients provided informed consent at the time of their CV clinic appointment; PGx testing was then ordered. Pharmacogenomic testing consisted of the Focused Pharmacogenomics panel which included 10 genes and 55 medications. RESULTS: Of the 272 patients screened, 100 (68% male) patients completed PGx testing (mean age 66.2 ± 9.6 years, mean Acute Physiology, Age and Chronic Health Evaluation III score 76.1 ± standard deviation). Pharmacogenomic results were available in the medical record within a median of 52.4 hours (interquartile range: 33.4-80.3). Pharmacogenomic testing results identified 5 CYP2C19 poor metabolizers, 26 CYP2C19 rapid metabolizers, 5 CYP2C19 ultrarapid metabolizers, 6 CYP2D6 poor metabolizers, 5 CYP2D6 poor to intermediate metabolizers, and 2 CYP2D6 rapid metabolizers identified. Overall, 98% of patients had actionable or potentially actionable PGx results, including 82% for warfarin, 65% for propafenone, 65% for tramadol, 46% for oxycodone, 45% for metoprolol, 33% for clopidogrel, 32% for proton pump inhibitors, 25% for statins, and 12% for haloperidol. CONCLUSIONS: A significant portion of patients had identified genetic variants that may warrant changes in medication management during and after CV-ICU stay. It remains to be seen if PGx testing leads to improvements in ICU patient outcomes.

Extended duration infusion of high-dose hydroxocobalamin for vasoplegic syndrome following cardiac surgery.

Vasoplegic syndrome occurs in 8% to 12% of cases that use cardiopulmonary bypass and carries a high mortality. Although the precise cause of this shock state has yet to determined, it is postulated to be related to abnormal nitric oxide (NO)-mediated dilatation of vascular smooth muscle resulting in arterial and venous vasodilatation. Since its first report in 2014, the off-label use of hydroxocobalmin as a rescue therapy for the treatment of refractory vasodilatory shock has gained attention with a mechanism thought to be primarily mediated by the scavenge, binding to, and prevention of the formation of NO. Importantly, no dose-finding study of hydroxocobalamin for the treatment of vasoplegic shock has been published. Consequently, dosing is extrapolated from the treatment of cyanide toxicity (5 g administered by intravenous infusion over 15 min) and the hemodynamic improvement only appears to persist for a few hours when administered as a bolus. Herein we describe twelve patients with vasoplegic shock following cardiac surgery that received an extended duration infusion of hydroxocobalamin administered over a median of 6 h and illustrate the rapidity and durability of the hemodynamic response encountered.

Anesthetic Management for Medialization Laryngoplasty Performed Under Concurrent Dexmedetomidine, Remifentanil, and Propofol Infusions.

INTRODUCTION: Type I thyroplasty, or medialization larygoplasty (ML), is a procedure which improves the voice by medializing a vocal fold with a permanent implant. Anesthetic management of these cases is challenging because patients can require periods of deep sedation followed by fully awake moments for phonation to assess the implant size. We present our experience of ML with or without arytenoid adduction (AA) using a multimodal anesthetic regimen consisting of concurrent infusions of dexmedetomidine, remifentanil, and propofol. METHODS: This is a retrospective case series of patients anesthetized using this protocol from June 1, 2015 through June 30, 2017. RESULTS: Seventy-five consecutive ML with or without AA patients anesthetized with dexmedetomidine and remifentanil infusions were identified, of which 74 (98.7%) also received concurrent propofol infusions. Mean duration of sedation was 190.9 ± 36.9 minutes and surgery was 139 ± 35.3 minutes. Transient hypopnea treated with supplemental oxygen complicated 18 (24%) cases and bradycardia requiring pharmacologic treatment complicated 3 (4%) cases. There were no other adverse anesthetic complications. One patient required surgical re-exploration due to postsurgical bleeding after the initial hospital discharge. CONCLUSION: In this cohort, a combination of remifentanil, dexmedetomidine and propofol infusions was well tolerated without serious adverse perioperative events.

Anesthetic management for medialization laryngoplasty using concurrent infusions of dexmedetomidine, remifentanil, and propofol versus controls.

PURPOSE: Medialization laryngoplasty (ML) ±â€¯arytenoid adduction (AA) surgery poses a unique anesthetic challenge that requires periods of deep sedation and patient cooperation with phonation to assess voice function. The purpose of this study was to assess if the protocolized administration of dexmedetomidine, remifentanil, and propofol (DRP) is associated with reduced procedural duration and administration of other sedating medications. MATERIALS AND METHODS: This was a retrospective 2:1 case matched study design; matched on age, sex, body mass index, AA, and surgical revision status. Data was obtained from the electronic medical record of a tertiary referral center. Cases underwent ML ±â€¯AA using DRP. Control subjects underwent surgery ML ±â€¯AA without DRP. RESULTS: 58 DRP cases (43.1% AA) were matched with 116 control patients (44.8% AA). DRP was associated with decreases in fentanyl dose (50 [25, 100] vs. 100 [50, 150] mcg; p < 0.01), incidence and dose of midazolam (4 [6.9%] vs. 70 [60.3%]; p < 0.01; 1 [1, 1] vs. 2 [2, 2]; p < 0.02), operative duration (131 ±â€¯33 vs. 160 ±â€¯50 min; p < 0.01), and anesthetic duration (182 ±â€¯35 vs. 219 ±â€¯60.3 min; p < 0.01). When adjusted for timeline, it was observed that case duration was declining prior to DRP introduction; this trend persisted after DRP introduction. Hypopnea was more common with DRP (14 [24.1%] vs. 7 [6.0%]; p < 0.01). CONCLUSIONS: DRP was associated with a substantial decrease in opioid and benzodiazepine administration. A reduction in procedural duration over time was also observed.

The use of flumazenil for benzodiazepine associated respiratory depression in postanesthesia recovery: risks and outcomes / O uso de flumazenil para depressão respiratória associada ao benzodiazepínico na recuperação pós-anestésica: riscos e resultados

Abstract Background and objectives The primary aim was to determine risk factors for flumazenil administration during postanesthesia recovery. A secondary aim was to describe outcomes among patients who received flumazenil. Methods Patients admitted to the postanesthesia recovery room at a large, academic, tertiary care facility after surgery under general anesthesia from January 1, 2010, to April 30, 2015, were identified and matched to 2 controls each, by age, sex, and surgical procedure. Flumazenil was administered in the recovery phase immediately after general anesthesia, according to the clinical judgment of the anesthesiologist. Demographic, procedural, and outcome data were extracted from the electronic health record. Conditional logistic regression, accounting for the 1:2 matched-set case-control study designs, was used to assess characteristics associated with flumazenil use. Results The incidence of flumazenil administration in the postanesthesia care unit was 9.9 per 10,000 (95% CI, 8.4-11.6) general anesthetics. History of obstructive sleep apnea (Odds Ratio [OR] = 2.27; 95% CI 1.02-5.09), longer anesthesia (OR = 1.13; 95% CI 1.03-1.24 per 30 minutes), use of total intravenous anesthesia (OR = 6.09; 95% CI 2.60-14.25), and use of benzodiazepines (OR = 8.17; 95% CI 3.71-17.99) were associated with risk for flumazenil administration. Among patients who received midazolam, cases treated with flumazenil received a higher median (interquartile range) dose than controls: 3.5 mg (2.0-4.0 mg) vs. 2.0 mg (2.0-2.0 mg), respectively (p < 0.001). Flumazenil use was correlated with a higher rate of unanticipated noninvasive positive pressure ventilation, longer postanesthesia care unit stay, and increased rate of intensive care unit admissions. Conclusions Patients who required flumazenil postoperatively had received a higher dosage of benzodiazepines and utilized more postoperative health care resources. More conservative perioperative use of benzodiazepines may improve postoperative recovery and use of health care resources.

Resumo Justificativa e objetivos Determinar os fatores de risco da administração de flumazenil durante a recuperação pós-anestésica e descrever os desfechos entre os pacientes que receberam flumazenil. Métodos Os pacientes admitidos em sala de recuperação pós-anestésica de um grande centro universitário em setor terciário de cuidados pós-cirurgia sob anestesia geral entre 1° de janeiro de 2010 e 30 de abril de 2015 foram identificados e pareados com dois controles cada por idade, sexo e procedimento cirúrgico. Flumazenil foi administrado na fase de recuperação imediatamente após a anestesia geral, de acordo com a avaliação clínica do anestesiologista. Os dados demográficos, dos procedimentos e dos desfechos foram extraídos do registro eletrônico de saúde. A regressão logística condicional para os desenhos do estudo de caso-controle pareado em 1:2 foi usada para avaliar as características associadas ao uso de flumazenil. Resultados A incidência da administração de flumazenil em sala de recuperação pós-anestésica foi de 9,9 por 10.000 (95% IC: 8,4-1,6) anestesias gerais. História da apneia obstrutiva do sono (razão de chances [OR] = 2,27; IC 95%: 1,02-5,09), anestesia de longa duração (OR = 1,13; IC 95%: 1,03-1,24 por 30 minutos), uso de anestesia intravenosa total (OR = 6,09; IC de 95%: 2,60-14,25) e uso de benzodiazepínicos (OR = 8,17; IC 95%: 3,71-17,99) foram associados a risco para a administração de flumazenil. Entre os pacientes que receberam midazolam, os casos tratados com flumazenil receberam uma dose mediana mais alta (intervalo interquartil) do que os controles: 3,5 mg (2,0-4,0 mg) vs. 2,0 mg (2,0-2,0 mg), respectivamente (p < 0,001). O uso de flumazenil foi correlacionado com uma taxa maior não prevista de ventilação não invasiva com pressão positiva, permanência mais longa em sala de recuperação pós-anestésica e aumento da taxa de admissões em unidade de terapia intensiva. Conclusão Os pacientes que precisaram de flumazenil no pós-operatório receberam uma dose maior de benzodiazepínicos e usaram mais recursos de cuidados da saúde no pós-operatório. O uso mais conservador de benzodiazepínicos no período perioperatório pode melhorar a recuperação e o uso de recursos de cuidados da saúde no pós-operatório.

[The use of flumazenil for benzodiazepine associated respiratory depression in postanesthesia recovery: risks and outcomes]. / O uso de flumazenil para depressão respiratória associada ao benzodiazepínico na recuperação pós­anestésica: riscos e resultados.

BACKGROUND AND OBJECTIVES: The primary aim was to determine risk factors for flumazenil administration during postanesthesia recovery. A secondary aim was to describe outcomes among patients who received flumazenil. METHODS: Patients admitted to the postanesthesia recovery room at a large, academic, tertiary care facility after surgery under general anesthesia from January 1, 2010, to April 30, 2015, were identified and matched to 2 controls each, by age, sex, and surgical procedure. Flumazenil was administered in the recovery phase immediately after general anesthesia, according to the clinical judgment of the anesthesiologist. Demographic, procedural, and outcome data were extracted from the electronic health record. Conditional logistic regression, accounting for the 1:2 matched-set case-control study designs, was used to assess characteristics associated with flumazenil use. RESULTS: The incidence of flumazenil administration in the postanesthesia care unit was 9.9 per 10,000 (95% CI, 8.4-11.6) general anesthetics. History of obstructive sleep apnea (Odds Ratio [OR]=2.27; 95% CI 1.02-5.09), longer anesthesia (OR=1.13; 95% CI 1.03-1.24 per 30minutes), use of total intravenous anesthesia (OR=6.09; 95% CI 2.60-14.25), and use of benzodiazepines (OR=8.17; 95% CI 3.71-17.99) were associated with risk for flumazenil administration. Among patients who received midazolam, cases treated with flumazenil received a higher median (interquartile range) dose than controls: 3.5mg (2.0-4.0mg) vs. 2.0mg (2.0-2.0mg), respectively (p<0.001). Flumazenil use was correlated with a higher rate of unanticipated noninvasive positive pressure ventilation, longer postanesthesia care unit stay, and increased rate of intensive care unit admissions. CONCLUSIONS: Patients who required flumazenil postoperatively had received a higher dosage of benzodiazepines and utilized more postoperative health care resources. More conservative perioperative use of benzodiazepines may improve postoperative recovery and use of health care resources.

Kinetic estimated glomerular filtration rate and acute kidney injury in cardiac surgery patients.

PURPOSE: To determine how a formula to estimate kinetically changing glomerular filtration rate (keGFR) relates to serum creatinine changes and to compare the discriminatory ability of keGFR to that of perioperative change in serum creatinine to predict acute kidney injury (AKI) and mortality. MATERIALS AND METHODS: Retrospective cohort study at a single-tertiary-care Midwestern university hospital of 4022 patients admitted to the intensive care unit between January 2006 and January 2012 immediately after cardiac surgery. MEASUREMENTS AND MAIN RESULTS: Of 4022 patients, 1031 (25.6%) developed at least AKI stage 1 and 1106 (27.5%) developed AKI-min. Patients who developed AKI stage 1 or AKI-min had a greater decrease in keGFR, both by absolute amounts and by percentage. After adjusting for other factors with logistic regression, keGFR had good discrimination (c statistic = 0.787 and 0.749, respectively) in predicting AKI and operative mortality. CONCLUSION: Despite no change in immediate perioperative serum creatinine levels, keGFR fell and this predicted subsequent AKI. Using keGFR enables identification of patients who, despite unchanged postoperative creatinine, incur clinically significant kidney injury based on reduction in GFR and increased mortality.