Internal jugular vein collapsibility does not predict fluid responsiveness in spontaneously breathing patients after cardiac surgery.

PURPOSE: The objective of our study was to evaluate the diagnostic accuracy of internal jugular vein (IJV) collapsibility as a predictor of fluid responsiveness in spontaneously breathing patients after cardiac surgery. METHODS: In this prospective observational study, spontaneously breathing patients were enrolled on the first postoperative day after coronary artery bypass grafting. Hemodynamic data coupled with simultaneous ultrasound assessment of the IJV were collected at baseline and after passive leg raising test (PLR). Continuous cardiac index (CI), stroke volume (SV), and stroke volume variation (SVV) were assessed with FloTracTM/EV1000™. Fluid responsiveness was defined as an increase in CI ≥ 10% after PLR. We compared the differences in measured variables between fluid responders and non-responders and tested the ability of ultrasonographic IJV indices to predict fluid responsiveness. RESULTS: Fifty-four patients were included in the study. Seventeen (31.5%) were fluid responders. The responders demonstrated significantly lower inspiratory and expiratory diameters of the IJV at baseline, but IJV collapsibility was comparable (P = 0.7). Using the cut-off point of 20%, IJV collapsibility predicted fluid responsiveness with a sensitivity of 76.5% and specificity of 38.9%, ROC AUC 0.55. CONCLUSION: In spontaneously breathing patients after surgical coronary revascularisation, collapsibility of the internal jugular vein did not predict fluid responsiveness.

A patient with pulmonary hypertension waiting for donor lungs during the pandemic: 194 days on extracorporeal life support including 143 days on pulmonary artery to left atrium shunt.

Patients with pulmonary hypertension and end-stage lung disease are fraught with high mortality while on a waiting list for lung transplant. With sometimes rapid deterioration they may require veno-arterial extracorporeal membrane oxygenation (VA-ECMO) as an immediate life-saving technique, which is a time-limited solution. The technique of pulmonary artery to left atrium (PA-LA) shunt fitted with an oxygenator enables bridging the patient to transplant for a longer time period. This low-resistance paracorporeal pumpless lung assist device allows for de-adaptation of the right ventricle back to lower afterload before the lung transplantation is carried out. The PA-LA shunt with an oxygenator also conveys a risk of multiple complications with reported median of 10-26 days until transplant. We report a case of pulmonary capillary hemangiomatosis in a 35-year-old female who had to wait for donor lungs during the pandemic of SARS-CoV-2 for 143 days on PA-LA shunt with oxygenator following 51 days on VA-ECMO. The extremely long course associated with multiple complications including three cerebral embolisms, episodes of sepsis and ingrowth of the return cannula into the left ventricular wall gives insight into the limits of this bridging technique.

Dual veno-arterial extra-corporeal membrane oxygenation support in a patient with refractory hyperdynamic septic shock: a case report.

The hypodynamic septic shock appears to be a promising indication to veno-arterial membrane oxygenation (VA-ECMO) support of a patient with insufficient cardiac output. With cardiac recovery most of those patients progress into a hyperdynamic septic shock with cardiac output, which may not match critically low systemic vascular resistance to maintain perfusion pressures. Such refractory distributive shock represents a challenging indication to VA-ECMO. We report a rare case of a 27-year old patient who developed severe refractory hypodynamic septic shock due to the bilateral staphylococcal pneumonia and had to be initially rescued by femoro-femoral VA-ECMO. Despite extensive measures, he remained in intractable hypotension and profound tissue hypoperfusion with imminent multiorgan failure. The commencement of a second jugulo-axillary VA ECMO secured a total blood flow of 14.3 L/min, which restored perfusion pressure and successfully bridged patient over the period of critical haemodynamic instability and ultimately may have facilitated recovery.

Extracorporeal Oxygenation Techniques in Adult Critical Airway Obstruction: A Review.

Extracorporeal life support has been increasingly utilized in different clinical settings to manage either critical respiratory or heart failure. Complex airway surgery with significant or even total perioperative airway obstruction represents an indication for this technique to prevent/overcome a critical period of severe hypoxaemia, hypoventilation, and/or apnea. This review summarizes the current published scientific evidence on the utility of extracorporeal respiratory support in airway obstruction associated with hypoxaemia, describes the available methods, their clinical indications, and possible limitations. Extracorporeal membrane oxygenation using veno-arterial or veno-venous mode is most commonly employed in such scenarios caused by endoluminal, external, or combined obstruction of the trachea and main bronchi.

Dendritic Cells in Subcutaneous and Epicardial Adipose Tissue of Subjects with Type 2 Diabetes, Obesity, and Coronary Artery Disease.

Dendritic cells (DCs) are professional antigen-presenting cells contributing to regulation of lymphocyte immune response. DCs are divided into two subtypes: CD11c-positive conventional or myeloid (cDCs) and CD123-positive plasmacytoid (pDCs) DCs. The aim of the study was to assess DCs (HLA-DR+ lineage-) and their subtypes by flow cytometry in peripheral blood and subcutaneous (SAT) and epicardial (EAT) adipose tissue in subjects with (T2DM, n = 12) and without (non-T2DM, n = 17) type 2 diabetes mellitus undergoing elective cardiac surgery. Subjects with T2DM had higher fasting glycemia (8.6 ± 0.7 vs. 5.8 ± 0.2 mmol/l, p < 0.001) and glycated hemoglobin (52.0 ± 3.4 vs. 36.9 ± 1.0 mmol/mol, p < 0.001) and tended to have more pronounced inflammation (hsCRP: 9.8 ± 3.1 vs. 5.1 ± 1.9 mg/ml, p = 0.177) compared with subjects without T2DM. T2DM was associated with reduced total DCs in SAT (1.57 ± 0.65 vs. 4.45 ± 1.56% for T2DM vs. non-T2DM, p = 0.041) with a similar, albeit insignificant, trend in EAT (0.996 ± 0.33 vs. 2.46 ± 0.78% for T2DM vs. non-T2DM, p = 0.171). When analyzing DC subsets, no difference in cDCs was seen between any of the studied groups or adipose tissue pools. In contrast, pDCs were increased in both SAT (13.5 ± 2.0 vs. 4.6 ± 1.9% of DC cells, p = 0.005) and EAT (29.1 ± 8.7 vs. 8.4 ± 2.4% of DC, p = 0.045) of T2DM relative to non-T2DM subjects as well as in EAT of the T2DM group compared with corresponding SAT (29.1 ± 8.7 vs. 13.5 ± 2.0% of DC, p = 0.020). Neither obesity nor coronary artery disease (CAD) significantly influenced the number of total, cDC, or pDC in SAT or EAT according to multiple regression analysis. In summary, T2DM decreased the amount of total dendritic cells in subcutaneous adipose tissue and increased plasmacytoid dendritic cells in subcutaneous and even more in epicardial adipose tissue. These findings suggest a potential role of pDCs in the development of T2DM-associated adipose tissue low-grade inflammation.

Coronary Artery Disease Is Associated with an Increased Amount of T Lymphocytes in Human Epicardial Adipose Tissue.

Immunocompetent cells including lymphocytes play a key role in the development of adipose tissue inflammation and obesity-related cardiovascular complications. The aim of the study was to explore the relationship between epicardial adipose tissue lymphocytes and coronary artery disease (CAD). To this end, we studied the content and phenotype of lymphocytes in peripheral blood, subcutaneous adipose tissue (SAT), and epicardial adipose tissue (EAT) in subjects with and without CAD undergoing elective cardiac surgery. Eleven subjects without CAD (non-CAD group) and 22 age-, BMI-, and HbA1C-matched individuals with CAD were included into the study. Blood, SAT, and EAT samples were obtained at the beginning of surgery. Lymphocyte populations were quantified as % of CD45+ cells using flow cytometry. Subjects with CAD had a higher total lymphocyte amount in EAT compared with SAT (32.24 ± 7.45 vs. 11.22 ± 1.34%, p = 0.025) with a similar trend observed in non-CAD subjects (29.68 ± 7.61 vs. 10.13 ± 2.01%, p = 0.067). T (CD3+) cells were increased (75.33 ± 2.18 vs. 65.24 ± 4.49%, p = 0.032) and CD3- cells decreased (21.17 ± 2.26 vs. 31.64 ± 4.40%, p = 0.028) in EAT of CAD relative to the non-CAD group. In both groups, EAT showed an elevated percentage of B cells (5.22 ± 2.43 vs. 0.96 ± 0.21%, p = 0.039 for CAD and 12.49 ± 5.83 vs. 1.16 ± 0.19%, p = 0.016 for non-CAD) and reduced natural killer (NK) cells (5.96 ± 1.32 vs. 13.22 ± 2.10%, p = 0.012 for CAD and 5.32 ± 1.97 vs. 13.81 ± 2.72%, p = 0.022 for non-CAD) relative to SAT. In conclusion, epicardial adipose tissue in subjects with CAD shows an increased amount of T lymphocytes relative to non-CAD individuals as well as a higher number of total and B lymphocytes and reduced NK cells as compared with corresponding SAT. These changes could contribute to the development of local inflammation and coronary atherosclerosis.

Management of accidental hypothermia: an established extracorporeal membrane oxygenation centre experience.

INTRODUCTION: Data on management of severe accidental hypothermia published from an established high-volume extracorporeal membrane oxygenation centre are scarce. METHODS: A total of 28 patients with intravesical temperature lower than 28°C on admission were either treated with veno-arterial extracorporeal membrane oxygenation or rewarmed conservatively. RESULTS: A total of 10 patients rewarmed on veno-arterial extracorporeal membrane oxygenation (age: 37 ± 12.6 years) and 18 conservatively (age: 55.2 ± 11.2 years) were collected over a course of 5 years. The dominant cause was alcohol intoxication with exposure to cold (39%), 12 patients were resuscitated prior to admission. The admission temperature in the extracorporeal membrane oxygenation group (23.8 ± 2.6°C) was lower than in the non-extracorporeal membrane oxygenation group (26.0 ± 1.5°C, p = 0.01). The peripheral percutaneous veno-arterial extracorporeal membrane oxygenation was always cannulated in malignant arrhythmias causing refractory cardiac arrest. The typical extracorporeal membrane oxygenation blood flow was 3-4 L/minute and sweep gas flow 2 L/minute, the median extracorporeal membrane oxygenation duration was 48.3 (28.1-86.7) hours. The median rates of rewarming did not differ (0.41 (0.35-0.7)°C/hour in extracorporeal membrane oxygenation and 0.77 (0.54-0.98)°C/hour in non-extracorporeal membrane oxygenation, p = 0.46) as well as the admission arterial lactate, pH and potassium. Their development was not different between the groups except for higher pH between the third and ninth hour of rewarming in the extracorporeal membrane oxygenation group. The hospital mortality was 10% in the extracorporeal membrane oxygenation group and 11.1% in the non-extracorporeal membrane oxygenation group with the median last Glasgow Coma Scale 15 and Cerebral Performance Score 1. CONCLUSION: Veno-arterial extracorporeal membrane oxygenation for severe hypothermia shows promising outcome data collected in an extracorporeal membrane oxygenation/extracorporeal cardiopulmonary resuscitation centre located in a European urban area. Except for presence of refractory cardiac arrest, the established hypothermia-related prognostic indicators did not differ between patients in need for extracorporeal membrane oxygenation and those rewarmed without extracorporeal membrane oxygenation.

Catastrophic Left Ventricular Thrombosis Complicating Extra-corporeal Membrane Oxygenation: A Case Report.

A massive left ventricular thrombosis represents a rare however, catastrophic complication of a central veno-arterial extra-corporeal membrane oxygenation. We report a case of such complication in a patient with severe left ventricular dysfunction after cardiac surgery. Its management and preventive measures are described and discussed.

Successful use of extra-corporeal membrane oxygenation in a patient with streptococcal sepsis: a case report and review of literature.

A young patient with streptococcal sepsis due to the phlegmon of his left thigh was admitted to the general intensive care unit. He developed a multi-organ failure and septic cardiomyopathy with subsequent cardiogenic shock. This resulted in hemodynamic instability unresponsive to conservative medical treatment. We report a successful application of veno-arterial extra-corporeal membrane oxygenation, which was used to overcome the period of critically low cardiac output caused by severe septic myocardial dysfunction.

The outcomes of patients with septic shock treated with propafenone compared to amiodarone for supraventricular arrhythmias are related to end-systolic left atrial volume.

AIMS: A recently published trial has shown no differences in outcomes between patients with new-onset supraventricular arrhythmia (SVA) in septic shock treated with either propafenone or amiodarone. However, these outcome data have not been evaluated in relation to the presence or absence of a dilated left atrium (LA). METHODS AND RESULTS: Patients with SVA and a left ventricular ejection fraction ≥ 35% were randomized to receive intravenous propafenone (70 mg bolus followed by 400-840 mg/24 h) or amiodarone (300 mg bolus followed by 600-1800 mg/24 h). They were divided into groups based on whether their end-systolic left atrial volume (LAVI) was ≥40 mL/m². The subgroup outcomes assessed were survival at ICU discharge, 1 month, 3 months, 6 months, and 12 months. Propafenone cardioverted earlier (P = 0.009) and with fewer recurrences (P = 0.001) in the patients without LA enlargement (n = 133). Patients with LAVI < 40 mL/m2 demonstrated a mortality benefit of propafenone over the follow-up of 1 year [Cox regression, hazard ratio (HR) 0.6 (95% CI 0.4; 0.9), P = 0.014]. Patients with dilated LA (n = 37) achieved rhythm control earlier in amiodarone (P = 0.05) with similar rates of recurrences (P = 0.5) compared to propafenone. The outcomes for patients with LAVI ≥ 40 mL/m2 were less favourable with propafenone compared to amiodarone at 1 month [HR 3.6 (95% CI 1.03; 12.5), P = 0.045]; however, it did not reach statistical significance at 1 year [HR 1.9 (95% CI 0.8; 4.4), P = 0.138]. CONCLUSION: Patients with non-dilated LA who achieved rhythm control with propafenone in the setting of septic shock had better short-term and long-term outcomes than those treated with amiodarone, which seemed to be more effective in patients with LAVI ≥ 40 mL/m². TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03029169, registered on 24 January 2017.

Update on Anticoagulation Strategies in Patients with ECMO-A Narrative Review.

The use of extracorporeal membrane oxygenation (ECMO) has recently increased exponentially. ECMO has become the preferred mode of organ support in refractory respiratory or circulatory failure. The fragile balance of haemostasis physiology is massively altered by the patient's critical condition and specifically the aetiology of the underlying disease. Furthermore, an application of ECMO conveys another disturbance of haemostasis due to blood-circuit interaction and the presence of an oxygenator. The purpose of this review is to summarise current knowledge on the anticoagulation management in patients undergoing ECMO therapy. The unfractionated heparin modality with monitoring of activated partial thromboplastin tests is considered to be a gold standard for anticoagulation in this specific subgroup of intensive care patients. However, alternative modalities with other agents are comprehensively discussed. Furthermore, other ways of monitoring can represent the actual state of coagulation in a more complex fashion, such as thromboelastometric/graphic methods, and might become more frequent. In conclusion, the coagulation system of patients with ECMO is altered by multiple variables, and there is a significant lack of evidence in this area. Therefore, a highly individualised approach is the best solution today.

Prediction of Fluid Responsiveness Using Combined End-Expiratory and End-Inspiratory Occlusion Tests in Cardiac Surgical Patients.

End-expiratory occlusion (EEO) and end-inspiratory occlusion (EIO) tests have been successfully used to predict fluid responsiveness in various settings using calibrated pulse contour analysis and echocardiography. The aim of this study was to test if respiratory occlusion tests predicted fluid responsiveness reliably in cardiac surgical patients with protective ventilation. This single-centre, prospective study, included 57 ventilated patients after elective coronary artery bypass grafting who were indicated for fluid expansion. Baseline echocardiographic measurements were obtained and patients with significant cardiac pathology were excluded. Cardiac index (CI), stroke volume and stroke volume variation were recorded using uncalibrated pulse contour analysis at baseline, after performing EEO and EIO tests and after volume expansion (7 mL/kg of succinylated gelatin). Fluid responsiveness was defined as an increase in cardiac index by 15%. Neither EEO, EIO nor their combination predicted fluid responsiveness reliably in our study. After a combined EEO and EIO, a cut-off point for CI change of 16.7% predicted fluid responsiveness with a sensitivity of 61.8%, specificity of 69.6% and ROC AUC of 0.593. In elective cardiac surgical patients with protective ventilation, respiratory occlusion tests failed to predict fluid responsiveness using uncalibrated pulse contour analysis.

Propafenone versus amiodarone for supraventricular arrhythmias in septic shock: a randomised controlled trial.

PURPOSE: Acute onset supraventricular arrhythmias can contribute to haemodynamic compromise in septic shock. Both amiodarone and propafenone are available interventions, but their clinical effects have not yet been directly compared. METHODS: In this two-centre, prospective controlled parallel group double blind trial we recruited 209 septic shock patients with new-onset arrhythmia and a left ventricular ejection fraction above 35%. The patients were randomised in a 1:1 ratio to receive either intravenous propafenone (70 mg bolus followed by 400-840 mg/24 h) or amiodarone (300 mg bolus followed by 600-1800 mg/24 h). The primary outcomes were the proportion of patients who had sinus rhythm 24 h after the start of the infusion, time to restoration of the first sinus rhythm and the proportion of patients with arrhythmia recurrence. RESULTS: Out of 209 randomized patients, 200 (96%) received the study drug. After 24 h, 77 (72.8%) and 71 (67.3%) were in sinus rhythm (p = 0.4), restored after a median of 3.7 h (95% CI 2.3-6.8) and 7.3 h (95% CI 5-11), p = 0.02, with propafenone and amiodarone, respectively. The arrhythmia recurred in 54 (52%) patients treated with propafenone and in 80 (76%) with amiodarone, p < 0.001. Patients with a dilated left atrium had better rhythm control with amiodarone (6.4 h (95% CI 3.5; 14.1) until cardioversion vs 18 h (95% CI 2.8; 24.7) in propafenone, p = 0.05). CONCLUSION: Propafenone does not provide better rhythm control at 24 h yet offers faster cardioversion with fewer arrhythmia recurrences than with amiodarone, especially in patients with a non-dilated left atrium. No differences between propafenone and amiodarone on the prespecified short- and long-term outcomes were observed.

Novel Methods for Predicting Fluid Responsiveness in Critically Ill Patients-A Narrative Review.

In patients with acute circulatory failure, fluid administration represents a first-line therapeutic intervention for improving cardiac output. However, only approximately 50% of patients respond to fluid infusion with a significant increase in cardiac output, defined as fluid responsiveness. Additionally, excessive volume expansion and associated hyperhydration have been shown to increase morbidity and mortality in critically ill patients. Thus, except for cases of obvious hypovolaemia, fluid responsiveness should be routinely tested prior to fluid administration. Static markers of cardiac preload, such as central venous pressure or pulmonary artery wedge pressure, have been shown to be poor predictors of fluid responsiveness despite their widespread use to guide fluid therapy. Dynamic tests including parameters of aortic blood flow or respiratory variability of inferior vena cava diameter provide much higher diagnostic accuracy. Nevertheless, they are also burdened with several significant limitations, reducing the reliability, or even precluding their use in many clinical scenarios. This non-systematic narrative review aims to provide an update on the novel, less employed dynamic tests of fluid responsiveness evaluation in critically ill patients.

Interpleural location of chest drain on ultrasound excludes pneumothorax and associates with a low degree of chest drain foreshortening on the antero-posterior chest X-ray.

BACKGROUND: The role of chest drain (CD) location by bedside imaging methods in the diagnosis of pneumothorax has not been explored in a prospective study yet. METHODS: Covid-19 ARDS patients with pneumothorax were prospectively monitored with chest ultrasound (CUS) and antero-posterior X-ray (CR) performed after drainage in the safe triangle. CD foreshortening was estimated as a decrease of chest drain index (CDI = length of CD in chest taken from CR/depth of insertion on CD scale + 5 cm). The angle of inclination of the CD was measured between the horizontal line and the CD at the point where it enters pleural space on CR. RESULTS: Of the total 106 pneumothorax cases 80 patients had full lung expansion on CUS, the CD was located by CUS in 69 (86%), the CDI was 0.99 (0.88-1.06). 26 cases had a residual pneumothorax after drainage (24.5%), the CD was located by CUS in 31%, the CDI was 0.76 (0.6-0.93),p < 0.01. The risk ratio for a pneumothorax in a patient with not visible CD between the pleural layers on CUS and an associated low CDI on CR was 5.97, p˂0.0001. For the patients with a steep angle of inclination (> 50°) of the CD, the risk ratio for pneumothorax was not significant (p < 0.17). A continued air leak from the CD after drainage is related to the risk for a residual pneumothorax (RR 2.27, p = 0.003). CONCLUSION: Absence of a CD on CUS post drainage, low CDI on CR and continuous air leak significantly associate with residual occult pneumothorax which may evade diagnosis on an antero-posterior CR.

Postoperative outcome in awake, on-pump, cardiac surgery patients.

PURPOSE: Thoracic epidural anesthesia (TEA) alone or combined with general anesthesia (TEA-GA) has been assumed to improve early postoperative outcome in cardiac surgery. The aim of our study was to investigate data of early and late postoperative outcome results of awake TEA patients undergoing cardiac surgery with comparison to patients under combined and general anesthesia (GA). METHODS: Forty-seven patients undergoing elective on-pump cardiac surgery were assigned to receive either epidural (group TEA, n = 17), combined (group TEA-GA, n = 15), or general (group GA, n = 15) anesthesia. Early and late postoperative outcome data, including hospital and 3-year mortality rates, were recorded and compared among the study groups. RESULTS: There was no major difference in early or late postoperative outcome data across all study groups, except for lower incidence of atrial fibrillation in the TEA group compared with the GA group (23.5% vs. 66.7%, respectively, P < 0.05). Also, TEA and TEA-GA groups compared with the GA group had lower pain visual analogue scale scores at 24 h postoperatively (4 ± 7, 6 ± 7, 14.7 ± 11, respectively, P < 0.05) and morphine requirements during the first 24 h after surgery (30 ± 6, 30 ± 6, 250 ± 140 µg/kg, respectively, P < 0.05). CONCLUSIONS: Based on our data, all three anesthetic methods were equivalent in terms of major determinants of postoperative outcome, except for lower incidence of atrial fibrillation in awake patients compared with patients under general anesthesia. Methods using postoperative epidural analgesia provided superior pain relief.

A Randomized Comparison of Non-Channeled GlidescopeTM Titanium Versus Channeled KingVisionTM Videolaryngoscope for Orotracheal Intubation in Obese Patients with BMI > 35 kg·m-2.

Videolaryngoscopes may improve intubating conditions in obese patients. A total of 110 patients with a body mass index > 35 kg∙m-2 were prospectively randomized to tracheal intubation using non-channeled Glidescope Titanium or channeled King Vision videolaryngoscope. The primary outcome was the time to tracheal intubation. Secondary outcomes included: total success rate, number of attempts, the quality of visualization, peri-procedural and post-proceduralcomplications. Time to the first effective breath was shorter with the King Vision (median; 95% CI)-36; 34-39 s vs. 42; 40-50 in the Glidescope group (p = 0.007). The total success rate was higher in the Glidescope group-100% vs. 89.1% (p = 0.03). There was a higher incidence of moderate and difficult laryngoscopy in the King Vision group. No difference was recorded in first attempt success rates, total number of attempts, use of additional maneuvers, intraoperative trauma, or any significant decrease in SpO2 during intubation. No serious complications were noted and the incidence of postoperative complaints was without difference. Although tracheal intubation with King Vision showed shorter time to the first breath, total success was higher in the Glidescope group, and all but one patients where intubation failed with the KingVision were subsequently intubated with the Glidescope.

Methylene blue administration in patients with refractory distributive shock - a retrospective study.

Hemodynamic effectiveness of methylene blue (MB) was tested in patients with refractory distributive shock. A retrospective analysis of 20 critically-ill patients who developed refractory shock was performed. Patients were divided into two study groups as responders with positive hemodynamic response to MB administration (defined as 10% decrease of norepinephrine dose) and non-responders. Hemodynamic, outcome data and baseline tissue hypoxia-related parameters including ratio of central venous-to-arterial carbon dioxide tension to arterio-venous oxygen content (P(v-a)CO2/C(a-v)O2) were compared between the groups. There were 9 (45%) responders and 11 (55%) non-responders to single bolus of MB administration. Dose of MB did not differ between responders and non-responders (1.3 ± 0.5 vs. 1.3 ± 0.4 mg/kg respectively, P = 0.979). MB responders had lower baseline P(v-a) CO2/C(a-v)O2 (1.79 ± 0.73 vs. 3.24 ± 1.18, P = 0.007), higher pH (7.26 ± 0.11 vs. 7.16 ± 0.10, P = 0.037) and lower lactate levels at 12 hours post MB administration (3.4 ± 2.7 vs. 9.9 ± 2.2 mmol/L, P = 0.002) compared to non-responders. Methylene blue represents a non-adrenergic vasopressor with only limited effectiveness in patients with refractory distributive shock. Profound tissue hypoxia with high degree of anaerobic metabolism was associated with the loss of hemodynamic responsiveness to its administration.