Use of methylene blue to treat vasoplegia syndrome in cystic fibrosis patients undergoing lung transplantation: A case series.

Background: Several studies have demonstrated the utility of methylene blue (MB) to treat vasoplegic syndrome (VS), but some have cautioned against its routine use in lung transplantation with only two cases described in prominent literature. Cystic fibrosis patients commonly have chronic infections which predispose them to a systemic inflammatory syndrome-like vasoplegic response during lung transplantation. We present 13 cystic fibrosis patients who underwent lung transplantation and received MB for vasoplegic syndrome while on cardiopulmonary bypass, with or without inhaled pulmonary vasodilator therapy. Methods: Single-center, retrospective, case series analysis of cystic fibrosis patients who underwent lung transplant and received MB for vasoplegia. We defined the primary outcome as 30-day mortality, and secondary outcomes as primary graft failure, 1-year mortality, postoperative complications, and hemodynamic response to MB. Results: MB was associated with a significant increase in mean arterial pressure (MAP) (P < 0.001) in all patients, and 84.6% (11/13) of the patients had either a decrease or no change in vasopressor requirement. No patients developed acute primary graft dysfunction and there was 100% 30-day and 1-year survival. One patient required Extracorporeal membrane oxygenation (ECMO) for hypoxemia and 69% (9/13) of the patients had evidence of postoperative right ventricular dysfunction, but no patients required a right ventricular assist device. Conclusion: This case series demonstrates the effectiveness of MB in treating vasoplegia in cystic fibrosis patients during lung transplantation, without evidence of primary graft dysfunction, 30-day or 1-year mortality. The safety of MB regarding hypoxemia and increased pulmonary vascular resistance requires further investigation.

Pheochromocytoma crisis precipitated by dexamethasone with profound lactic acidosis, but without severe hypertension.

Summary: We describe a case of a 47-year-old patient who presented with severe lactic acidosis, troponinemia, and acute kidney injury after receiving 8 mg of intramuscular dexamethasone for seasonal allergies in the setting of an undiagnosed epinephrine-secreting pheochromocytoma. This case was atypical, however, in that the patient exhibited only mildly elevated noninvasive measured blood pressures. Following a period of alpha-adrenergic blockade, the tumor was resected successfully. Steroid administration can precipitate pheochromocytoma crisis that may present unusually as in our patient with mild hypertension but profound lactic acidosis. Learning points: Steroids administered via any route can precipitate pheochromocytoma crisis, manifested by excessive catecholamine secretion and associated sequelae from vasoconstriction. Lack of moderate/severe hypertension on presentation detracts from consideration of pheochromocytoma as a diagnosis. Lactatemia after steroid administration should prompt work-up for pheochromocytoma, as it can be seen in epinephrine-secreting tumors. Noninvasive blood pressure measurements may be unreliable during pheochromocytoma crisis due to excessive peripheral vasoconstriction.

Perioperative Implications of the 2020 American Heart Association Scientific Statement on Drug-Induced Arrhythmias-A Focused Review.

The recently released American Heart Association (AHA) scientific statement on drug-induced arrhythmias discussed medications commonly associated with bradycardia, supraventricular tachycardias, and ventricular arrhythmias. The foundational data for this statement were collected from general outpatient and inpatient populations. Patients undergoing surgical and minimally invasive treatments are a unique subgroup, because they may experience hemodynamic changes associated with anesthesia and their procedure, receive multiple drug combinations not given in either inpatient or outpatient settings, or experience postprocedural inflammatory syndromes. Accordingly, the generalizability of the AHA scientific statement to this perioperative population is unclear. This focused review highlights important aspects of the new AHA scientific statement and their application to the perioperative setting. The authors review medications frequently encountered and given by anesthesiologists and their risk of drug-induced arrhythmias and discuss common anesthetic and adjunctive medications and their associated risks of bradycardia, atrial fibrillation, torsades de pointes, and drug-induced Brugada syndrome. In many instances, the risk of arrhythmia reported by the AHA scientific statement in the general population appeared to be higher than found in perioperative arenas. Furthermore, the authors discuss the arrhythmia risk of additional medications commonly ordered or administered by anesthesiologists that are not included in the AHA scientific statement. As patient and procedural complexity increases and novel anesthetic combinations propagate, further research and observational studies will be required to delineate further perioperative risks for drug-induced arrhythmia.

Unexpected Interruptions in the Inhaled Epoprostenol Delivery System: Incidence of Adverse Sequelae and Therapeutic Consequences in Critically Ill Patients.

OBJECTIVES: Inhaled epoprostenol is a continuously delivered selective pulmonary vasodilator that is used in patients with refractory hypoxemia, right heart failure, and postcardiac surgery pulmonary hypertension. Published data suggest that inhaled epoprostenol administration via vibrating mesh nebulizer systems may lead to unexpected interruptions in drug delivery. The frequency of these events is unknown. The objective of this study was to describe the incidence and clinical consequences of unexpected interruption in critically ill patients. DESIGN: Retrospective review and analysis. SETTING: Stanford University Hospital, a 605-bed tertiary care center. PATIENTS: Patients receiving inhaled epoprostenol in 2019. INTERVENTIONS: No interventions. MEASUREMENTS AND MAIN RESULTS: Clinical indication, duration of inhaled epoprostenol delivery, mode of respiratory support, and documented unexpected interruption. In 2019, there were 493 administrations of inhaled epoprostenol in 433 unique patients. Primary indications for inhaled epoprostenol were right heart dysfunction (n = 394; 79.9%) and hypoxemia (n = 92; 18.7%). Unexpected delivery interruptions occurred in 31 administrations (6.3%). Median duration of therapy prior to unexpected interruption was 2 days (interquartile range, 2-5 d). Respiratory support at the time of unexpected interruption was mechanical ventilation (61.3%), high-flow nasal cannula (35.5%), and noninvasive positive pressure ventilation (3.2%). Adverse sequelae of unexpected interruption included elevated pulmonary artery pressures (n = 12), systemic hypotension (n = 8), hypoxemia (n = 8), elevated central venous pressure (n = 4), and cardiac arrest (n = 1). Therapeutic interventions following unexpected interruption included initiation of inhaled nitric oxide (n = 21), increase in vasoactive medication (n = 2), and increase in respiratory support (n = 2). Most of the adverse events were Common Terminology Criteria for Adverse Events grade 3 and 4 (93.5%). CONCLUSIONS: A retrospective review of patients receiving inhaled epoprostenol via vibrating mesh nebulizer in 2019 revealed interruptions in 6.3% of administrations with most of these interruptions requiring therapeutic intervention. The true incidence of unexpected interruption and subsequent rate of unexpected interruption's requiring intervention is unknown due to the reliance on unexpected interruption identification and subsequent documentation in the electronic medical record. Sudden interruption in inhaled epoprostenol delivery can result in severe cardiopulmonary compromise, and on rare occasion, death.

Death From Primary Amebic Meningoencephalitis After Recreational Water Exposure During Recent Travel to India-Santa Clara County, California, 2020.

BACKGROUND: In February 2020, a man returned to the United States after an 11-day trip to India and died of primary amebic meningoencephalitis (PAM), caused by nasal exposure to the free-living ameba Naegleria fowleri found in warm water. We identified potential exposures, confirmed etiology, and described the molecular epidemiology of the infection. METHODS: We reviewed medical records to describe his clinical course and interviewed his family to determine water exposures. Genotyping was performed on the N. fowleri strain and compared with North American strains through repetitive nonpolymorphic nuclear loci analysis to identify differences. We reviewed N. fowleri strains in the National Center for Biotechnology Information database (GenBank) to determine genotypes present in India. RESULTS: The patient became acutely encephalopathic 3 days after returning; the only known nasal water exposure was at an indoor swimming pool in India 5 days earlier. Cerebrospinal fluid (CSF) testing demonstrated neutrophil-predominant pleocytosis and low glucose, but negative gram stain and culture. CSF microscopy revealed trophozoites; N. fowleri was detected by real-time polymerase chain reaction. Classical genotyping confirmed genotype I, common in the United States and among Indian strains in GenBank. The North American N. fowleri strains and the patient's strain varied at 5 nonpolymorphic loci. CONCLUSIONS: A man died from PAM after likely exposure at a vacation rental pool in India. We recommend including PAM in the differential diagnosis when CSF studies suggest bacterial meningitis but gram stain is negative. Genotyping can advance our understanding of N. fowleri molecular epidemiology and support future investigations.

First lung and kidney multi-organ transplant following COVID-19 Infection.

As the world responds to the global crisis of the COVID-19 pandemic an increasing number of patients are experiencing increased morbidity as a result of multi-organ involvement. Of these, a small proportion will progress to end-stage lung disease, become dialysis dependent, or both. Herein, we describe the first reported case of a successful combined lung and kidney transplantation in a patient with COVID-19. Lung transplantation, isolated or combined with other organs, is feasible and should be considered for select patients impacted by this deadly disease.

The Use of Factor Eight Inhibitor Bypass Activity (FEIBA) for the Treatment of Perioperative Hemorrhage in Left Ventricular Assist Device Implantation.

OBJECTIVE: To test the hypothesis that factor eight inhibitor bypassing activity (FEIBA) can be used to control bleeding following left ventricular assist device (LVAD) implantation without increasing the 14-day composite thrombotic outcome of pump thrombus, ischemic cerebrovascular accidents, pulmonary embolism, and deep venous thrombosis. DESIGN: Retrospective cohort study. SETTING: Academic hospital. PARTICIPANTS: Three hundred nineteen consecutive patients who underwent LVAD implantation (December 1, 2009 to December 30, 2018). INTERVENTION: FEIBA administered to control perioperative hemorrhage. MEASUREMENTS AND MAIN RESULTS: The 82 patients (25.7%) in the FEIBA cohort had more risk factors for perioperative hemorrhage, such as lower preoperative platelet count (169 ± 66 v 194 ± 68 × 103/mL, p = 0.004), prior cardiac surgery (36.6% v 21.9%, p = 0.008), and longer cardiopulmonary bypass (CPB) time (100.3 v 75.2 minutes, p = 0.001) than the 237 controls. After 16.6 units (95% CI: 14.3-18.9) of blood products were given, 992 units (95% CI: 821-1163) of FEIBA were required to control bleeding in the FEIBA cohort. Compared to the controls, there were no differences in the 14-day composite thrombotic outcome (11.0% v 7.6%, p = 0.343) or mortality rate (3.7% v 1.3%, p = 0.179). Multivariate logistical regression identified preoperative international normalized ratio (odds ratio [OR]: 1.30, 95% CI: 1.04-1.62) and CPB time (OR: 1.11, 95% CI: 1.02-1.20) as risk factors for 14-day thrombotic events, but FEIBA usage was not associated with an increased risk. CONCLUSIONS: In this retrospective cohort study, the use of FEIBA (∼1,000 units, ∼13 units/kg) to control perioperative hemorrhage following LVAD implantation was not associated with increases in mortality or composite thrombotic outcome.

Specific Considerations for Venovenous Extracorporeal Membrane Oxygenation During Coronavirus Disease 2019 Pandemic.

Extracorporeal membrane oxygenation (ECMO) is recognized as organ support for potentially reversible acute respiratory distress syndrome (ARDS). However, limited resource during the outbreak and the coagulopathy associated with coronavirus disease 2019 (COVID-19) make the utilization of venovenous (VV) ECMO highly challenging. We herein report specific considerations for cannulation configurations and ECMO management during the pandemic. High blood flow and anticoagulation at higher levels than usual practice for VV ECMO may be required because of thrombotic hematologic profile of COVID-19. Among our first 24 cases (48.8 ± 8.9 years), 17 patients were weaned from ECMO after a mean duration of 19.0 ± 10.1 days and 16 of them have been discharged from ICU.

Rescue of Nimodipine-Induced Refractory Vasoplegia With Hydroxocobalamin in Subarachnoid Hemorrhage: A Case Report.

BACKGROUND: We report a case of refractory vasoplegia after nimodipine administration that was unresponsive to triple vasopressor therapy and was rescued by IV hydroxocobalamin. CASE SUMMARY: An 84-year-old male presented comatose from a subarachnoid hemorrhage and developed severe hypotension unresponsive to three vasopressors following a single dose of enteral nimodipine. Multisystem point-of-care ultrasonography ruled out alternate etiologies of shock, indicating that this was likely a vasoplegic state caused by nimodipine. We administered 5 grams of IV hydroxocobalamin over 15 minutes due to the possibility of impaired nitric oxide metabolism as the driver of vasoplegia. This led to immediate improvement in hemodynamics and rapid discontinuation of vasopressors. The patient experienced chromaturia but no other adverse effects due to hydroxocobalamin. CONCLUSIONS: Nimodipine administration is a standard practice for patients with aneurysmal subarachnoid hemorrhage to reduce unfavorable outcomes from cerebral vasospasm. Although mild hypotension is a common side effect of nimodipine, in rare cases, it may become profound, leading to refractory vasoplegia. There is no evidence-base for reversal agents for nimodipine-induced vasoplegia, and this case is the first to demonstrate successful use of hydroxocobalamin as a potential rescue therapy. We also propose an algorithm for treatment of vasoplegia with consideration of medications that act on nitric oxide-mediated vasodilation and their side-effect profiles.

Catecholamine-induced cerebral vasospasm and multifocal infarctions in pheochromocytoma.

SUMMARY: We report the case of a 76-year-old male with a remote history of papillary thyroid cancer who developed severe paroxysmal headaches in the setting of episodic hypertension. Brain imaging revealed multiple lesions, initially of inconclusive etiology, but suspicious for metastatic foci. A search for the primary malignancy revealed an adrenal tumor, and biochemical testing confirmed the diagnosis of a norepinephrine-secreting pheochromocytoma. Serial imaging demonstrated multiple cerebral infarctions of varying ages, evidence of vessel narrowing and irregularities in the anterior and posterior circulations, and hypoperfusion in watershed areas. An exhaustive work-up for other etiologies of stroke including thromboembolic causes or vasculitis was unremarkable. There was resolution of symptoms, absence of new infarctions, and improvement in vessel caliber after adequate alpha-adrenergic receptor blockade for the management of pheochromocytoma. This clinicoradiologic constellation of findings suggested that the etiology of the multiple infarctions was reversible cerebral vasoconstriction syndrome (RCVS). Pheochromocytoma remains a poorly recognized cause of RCVS. Unexplained multifocal cerebral infarctions in the setting of severe hypertension should prompt the consideration of a vasoactive tumor as the driver of cerebrovascular dysfunction. A missed or delayed diagnosis has the potential for serious neurologic morbidity for an otherwise treatable condition. LEARNING POINTS: The constellation of multifocal watershed cerebral infarctions of uncertain etiology in a patient with malignant hypertension should trigger the consideration of undiagnosed catecholamine secreting tumors, such as pheochromocytomas and paragangliomas. Reversible cerebral vasoconstriction syndrome is a serious but reversible cerebrovascular manifestation of pheochromocytomas that may lead to strokes (ischemic and hemorrhagic), seizures, and cerebral edema. Alpha-adrenergic receptor blockade can reverse cerebral vasoconstriction and prevent further cerebral ischemia and infarctions. Early diagnosis of catecholamine secreting tumors has the potential for reducing neurologic morbidity and mortality in patients presenting with cerebrovascular complications.

Mortality of Patients Requiring Escalation to Intensive Care within 24 Hours of Admission in a Mixed Medical-Surgical Population.

OBJECTIVE: Delayed intensive care unit (ICU) admissions are associated with increased mortality. We present a retrospective study looking at whether indirect admissions to the ICU within 24 hours of hospital admission were associated with increased mortality. DESIGN: Retrospective cohort study SETTING: Mixed medical-surgical ICU at a large tertiary United States Veterans Affairs (VA) Hospital System POPULATION: The patients were a mix of medical and surgical patients. Patients included both those directly admitted from the operating room as well as those escalated to the ICU after initial admission to the ward (indirect admission). METHODS: All admissions to a medical-surgical ICU from 2008 to 2013 were included in the study. The database was queried for time and location where the admission originated. Separate lists were created for patients with severe sepsis, patients who transferred to the ICU within the first 24 hours, and patients who had rapid response or code team activations. Analysis was applied to the whole group and to medical and surgical subpopulations. RESULTS: A total of 3,862 ICU admissions were studied. Univariate analysis indicated an impact of delayed admission on whole group and surgical patients; however, multivariate analysis indicated a significant effect of delayed admission on 1-year surgical mortality. Multivariate analysis also showed a consistent effect of age, ICU length of stay, and cardiac arrest on mortality of both medical and surgical ICU patients. CONCLUSION: In a large retrospective study, surgical patients had increased 1-year mortality if they required escalation to the ICU within 24 hours of hospital admission. This result was not replicated in medical patients, possibly related to a burden of illness that could not be altered by earlier care.

Retrospective Analysis of Peri-Intubation Hypoxemia During the Coronavirus Disease 2019 Epidemic Using a Protocol for Modified Airway Management.

This single-center retrospective study evaluated a protocol for the intubation of patients with confirmed or suspected coronavirus disease 2019 (COVID-19). Twenty-one patients were intubated, 9 of whom were found to have COVID-19. Adherence to the airway management protocol was high. COVID-19 patients had lower peripheral capillary oxygen saturation by pulse oximetry (Spo2) nadirs during intubation (Spo2, 73% [72%-77%] vs 89% [86%-94%], P = .024), and a greater percentage experienced severe hypoxemia defined as Spo2 ≤80% (89% vs 25%, P = .008). The incidence of severe hypoxemia in COVID-19 patients should be considered in the development of guidelines that incorporate high-flow nasal cannula and noninvasive positive pressure ventilation.