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.

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.

Effect of Intra-arrest Transport, Extracorporeal Cardiopulmonary Resuscitation, and Immediate Invasive Assessment and Treatment on Functional Neurologic Outcome in Refractory Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial.

Importance: Out-of-hospital cardiac arrest (OHCA) has poor outcome. Whether intra-arrest transport, extracorporeal cardiopulmonary resuscitation (ECPR), and immediate invasive assessment and treatment (invasive strategy) is beneficial in this setting remains uncertain. Objective: To determine whether an early invasive approach in adults with refractory OHCA improves neurologically favorable survival. Design, Setting, and Participants: Single-center, randomized clinical trial in Prague, Czech Republic, of adults with a witnessed OHCA of presumed cardiac origin without return of spontaneous circulation. A total of 256 participants, of a planned sample size of 285, were enrolled between March 2013 and October 2020. Patients were observed until death or day 180 (last patient follow-up ended on March 30, 2021). Interventions: In the invasive strategy group (n = 124), mechanical compression was initiated, followed by intra-arrest transport to a cardiac center for ECPR and immediate invasive assessment and treatment. Regular advanced cardiac life support was continued on-site in the standard strategy group (n = 132). Main Outcomes and Measures: The primary outcome was survival with a good neurologic outcome (defined as Cerebral Performance Category [CPC] 1-2) at 180 days after randomization. Secondary outcomes included neurologic recovery at 30 days (defined as CPC 1-2 at any time within the first 30 days) and cardiac recovery at 30 days (defined as no need for pharmacological or mechanical cardiac support for at least 24 hours). Results: The trial was stopped at the recommendation of the data and safety monitoring board when prespecified criteria for futility were met. Among 256 patients (median age, 58 years; 44 [17%] women), 256 (100%) completed the trial. In the main analysis, 39 patients (31.5%) in the invasive strategy group and 29 (22.0%) in the standard strategy group survived to 180 days with good neurologic outcome (odds ratio [OR], 1.63 [95% CI, 0.93 to 2.85]; difference, 9.5% [95% CI, -1.3% to 20.1%]; P = .09). At 30 days, neurologic recovery had occurred in 38 patients (30.6%) in the invasive strategy group and in 24 (18.2%) in the standard strategy group (OR, 1.99 [95% CI, 1.11 to 3.57]; difference, 12.4% [95% CI, 1.9% to 22.7%]; P = .02), and cardiac recovery had occurred in 54 (43.5%) and 45 (34.1%) patients, respectively (OR, 1.49 [95% CI, 0.91 to 2.47]; difference, 9.4% [95% CI, -2.5% to 21%]; P = .12). Bleeding occurred more frequently in the invasive strategy vs standard strategy group (31% vs 15%, respectively). Conclusions and Relevance: Among patients with refractory out-of-hospital cardiac arrest, the bundle of early intra-arrest transport, ECPR, and invasive assessment and treatment did not significantly improve survival with neurologically favorable outcome at 180 days compared with standard resuscitation. However, the trial was possibly underpowered to detect a clinically relevant difference. Trial Registration: ClinicalTrials.gov Identifier: NCT01511666.

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 membrane oxygenation survival: External validation of current predictive scoring systems focusing on influenza A etiology.

Despite increasing clinical experience with extracorporeal membrane oxygenation (ECMO), its optimal indications remain unclear. Here, we externally evaluated all currently available ECMO survival-predicting scoring systems and the APACHE II score in subjects undergoing veno-venous ECMO (VV ECMO) support due to acute respiratory distress syndrome (ARDS) with influenza (IVA) and non-influenza (n-IVA) etiologies. Our aim was to find the best scoring system for influenza A ARDS ECMO success prediction. Retrospective data were analyzed to assess the abilities of the PRESERVE, RESP, PRESET, ECMOnet, Roch, and APACHE II scores to predict patient outcome. Patients treated with veno-venous ECMO support for ARDS were divided into two groups: IVA and n-IVA etiologies. Parameters collected within 24 hours before ECMO initiation were used to calculate PRESERVE, RESP, PRESET, ECMOnet, Roch, and APACHE II scores. Compared to the IVA group, the n-IVA group exhibited significantly higher ICU, 28-day, and 6-month mortality (P = .043, .034, and .047, respectively). Regarding ECMO support success predictions, the area under the receiver operating characteristic curve (AUC) was 0.62 for PRESERVE, 0.44 for RESP, 0.57 for PRESET, and 0.67 for ECMOnet, and 0.62 for Roch calculated for all subjects according to the original papers. In the IVA group, APACHE II had the best predictive value for ICU, hospital, 28-day, and 6-month mortality (AUC values of 0.73, 0.73, 0.70, and 0.73, respectively). In the n-IVA group, APACHE II was the best predictor of survival in the ICU and hospital (AUC 0.54 and 0.57, respectively). From all possible ECMO survival scoring systems, the APACHE II score had the best predictive value for VV ECMO subjects with ARDS caused by influenza A-related pneumonia with a cut-off value of about 32 points.

Peripheral polyneuropathy after acute methanol poisoning: Six-year prospective cohort study.

BACKGROUND: Methanol is a widely used industrial short-chain aliphatic alcohol with known neurotoxic properties. Mass poisoning outbreaks due to the consumption of methanol-adulterated alcoholic drinks present a challenge to healthcare providers due to the high mortality and serious central nervous system (CNS) damage in survivors. However, the impact of methanol exposure on the peripheral nervous system is unknown. OBJECTIVES: To investigate the role of acute methanol exposure in the development of peripheral polyneuropathy (PNP) during the years following discharge from the hospital. METHODS: A total of 55 patients with confirmed methanol poisoning (mean age of 47.9 ± 3.6 years; 9 females) were examined 4 times within a 6-year prospective longitudinal cohort study. The program included neurological and electromyographic examinations, visual evoked potentials, ocular examinations with retinal nerve fibre layer thickness measurements, brain magnetic resonance imaging, and a series of biochemical and toxicological tests. RESULTS: PNP was observed in 20/55 (36 %) patients, which, in most of the cases, was mild axonal sensorimotor neuropathy. In 8/55 (15 %) patients, worsening of electromyographic findings was registered during the follow-up period, including 5 cases with newly diagnosed PNP and 3 cases of PNP progression. In one subject, complete reversal of PNP was registered after cessation of alcohol intake. The patients with PNP were significantly older (57.3 ± 5.3 versus 42.5 ± 3.9 years; p < 0.001), with higher blood glucose (5.93 ± 0.97 versus 4.81 ± 0.32 mmol/L; p = 0.035) and lower vitamin B1 (45.5 ± 7.4 versus 57.5 ± 5.2 ug/L; p = 0.015) concentrations. The number of chronic alcohol abusers was significantly higher in the PNP group (17/20 versus 20/35; p = 0.034). No associations between PNP prevalence/ dynamics and acute parameters of poisoning severity, arterial blood pH (7.26 ± 0.07 with PNP versus 7.18 ± 0.09 without PNP; p = 0.150), or serum methanol (1320.0 ± 700.0 with PNP versus 1430.0 ± 510.0 mg/L without PNP; p = 0.813) and ethanol (460.0 ± 560.0 with PNP versus 340.0 ± 230.0 mg/L without PNP; p = 0.675) concentrations at admission were found. No difference in the number of patients with visual (9/20 with PNP versus 12/35 patients without PNP; p = 0.431) and CNS sequelae (9/20 with PNP versus 15/35 patients without PNP; p = 0.877) of poisoning was present. DISCUSSION: Despite the relatively high number of PNP cases, no association was found between the severity of acute methanol poisoning and the prevalence of PNP and its dynamics during six years of observation. We did not find an association between methanol-induced visual/ brain damage and the prevalence of PNP in survivors of poisoning. A high prevalence of PNP and its progression might be attributed to other causes, mainly a history of chronic alcohol abuse and insufficiently treated diabetes mellitus. Our results highlight the importance of complete cessation of alcohol consumption and better control of glycaemia in diabetic patients in the prevention and treatment of peripheral PNP.

Health-related quality of life determinants in survivors of a mass methanol poisoning outbreak: six-year prospective cohort study.

Purpose: The effect of acute methanol poisoning on the follow-up quality of life of survivors in mass poisoning outbreaks is not known. The objective of this is to study the impact of visual and central nervous system (CNS) sequelae of methanol poisoning on long-term health-related quality of life (QoL) of survivors, its clinical determinants, and dynamics.Materials and methods: A total of 54 patients with confirmed methanol poisoning (mean age 46.7 ± 13.4 years, 9 females) were examined consequently three times within six-year prospective cohort study and compared to 23 controls with the history of chronic alcohol abuse. The following tests were performed: SF-36 QoL questionnaire, visual evoked potentials (VEP) of optic nerve, ocular examination with retinal nerve fiber layer (RNFL) thickness measurement, brain magnetic resonance imaging (MRI), and biochemical and toxicological tests.Results: Acute methanol poisoning led to significant decrease in physical component summary (PCS) compared to PCS of age-adjusted controls (mean score with SD 46.8 ± 11.0 versus 52.3 ± 9.4 points; p = .003). In 17/40 (42.5%) patients with three rounds of examination, signs of severe disability (≤30 points in at least one score) were present six years after discharge, with negative dynamics of PCS score during the observation period. The patients with abnormal RNFL thickness had lower PCS (mean difference 10.5 points; 95%CI 3.5-17.5, p = .004) and mental component summary score (9.5 points; 95%CI 1.9-17.1, p = .015) compared to the patients with normal RNFL. Signs of physical and mental adaptation to long-term visual sequelae were registered with gradual reduction of difference in most of physical and mental components scores compared to the patients with normal RNFL during six years of observation. Signs of hemorrhagic brain lesions were associated with permanent decrease of PCS score (mean difference 7.4 points; 95%CI 0.6-14.0; p = .033), bodily pain (8.7 points; 95%CI 1.6-17.6; p = .018), and social functioning (8.2 points; 95%CI 3.0-17.4; p = .005) six years after discharge. No effect of type of antidote (fomepizole versus ethanol) and extracorporeal enhanced elimination modality (intermittent hemodialysis versus continuous renal replacement therapy) applied in hospital on long-term QoL was found (all p > .05).Conclusion: Acute methanol poisoning was associated with a significant decrease of health-related quality of life of survivors persisting for at least six years after discharge. The more pronounced decrease in QoL scores was observed in the patients with hemorrhagic brain lesions and visual sequelae of poisoning with abnormal RNFL thickness.

The impact of co-morbidities on a 6-year survival after methanol mass poisoning outbreak: possible role of metabolic formaldehyde.

Context: The influence of co-morbid conditions on the outcome of acute methanol poisoning in mass poisoning outbreaks is not known.Objective: The objective of this is to study the impact of burden of co-morbidities, complications, and methanol-induced brain lesions on hospital, follow-up, and total mortality.Methods: All patients hospitalized with methanol poisoning during a mass poisoning outbreak were followed in a prospective cohort study until death or final follow-up after 6 years. The age-adjusted Charlson co-morbidity index (ACCI) score was calculated for each patient. A multivariate Cox regression model was used to calculate the adjusted hazards ratio (HR) for death. The survival was modeled using the Kaplan-Meier method.Results: Of 108 patients (mean age with SD 50.9 ± 2.6 years), 24 (54.4 ± 5.9 years) died during hospitalization (mean survival with SD 8 ± 4 days) and 84 (49.9 ± 3.0 years; p = .159) were discharged, including 27 with methanol-induced brain lesions. Of the discharged patients, 15 (56.3 ± 6.8 years) died during the follow-up (mean survival 37 ± 11 months) and 69 (48.5 ± 3.3 years; p = .044) survived. The hospital mortality was 22%, the follow-up mortality was 18%; the total mortality was 36%. Cardiac/respiratory arrest, acute respiratory failure, multiorgan failure syndrome, and arterial hypotension increased the HR for hospital and total (but not follow-up) mortality after adjustment for age, sex, and arterial pH (all p < .05). All patients who died in the hospital had at least one complication. A higher ACCI score was associated with greater total mortality (HR 1.22; 1.00-1.48 95% CI; p = .046). Of those who died, 35 (90%) had a moderate-to-high ACCI. The Kaplan-Meier curve demonstrated that patients with a high ACCI had greater follow-up mortality compared to ones with low (p = .027) or moderate (p = .020) scores. For the patients who died during follow-up, cancers of different localizations were responsible for 7/15 (47%) of the deaths.Conclusions: The character and number of complications affected hospital but not follow-up mortality, while the burden of co-morbidities affected follow-up mortality. Methanol-induced brain lesions did not affect follow-up mortality. Relatively high cancer mortality rate may be associated with acute exposure to metabolic formaldehyde produced by methanol oxidation.

Efficacy and safety of 1C class antiarrhythmic agent (propafenone) for supraventricular arrhythmias in septic shock compared to amiodarone: protocol of a prospective randomised double-blind study.

INTRODUCTION: Supraventricular arrhythmias contribute to haemodynamic compromise in septic shock. A retrospective study generated the hypothesis that propafenone could be more effective than amiodarone in achieving and maintaining sinus rhythm (SR). Certain echocardiographic parameters may predict a successful cardioversion and help in the decision on rhythm or rate control strategy. METHODS AND ANALYSIS: The trial includes septic shock patients with new-onset arrhythmia, but without severe impairment of the left ventricular ejection fraction. After baseline echocardiography, the patient is randomised to receive a bolus and maintenance dose of either amiodarone or propafenone. The primary outcome is the proportion of patients that have achieved rhythm control at 24 hours after the start of the infusion. The secondary outcomes are the percentages of patients that needed rescue treatments (DC cardioversion or unblinding and crossover of the antiarrhythmics), the recurrence of arrhythmias, intensive care unit mortality, 28-day and 1-year mortality. In the posthoc analysis, we separately assess subgroups of patients with pulmonary hypertension and right ventricular dysfunction. In the exploratory part of the study, we assess whether the presence of a transmitral diastolic A wave and its higher velocity-time integral is predictive for the sustainability of mechanical SR and whether the indexed left atrial endsystolic volume is predictive of recurrent arrhythmia. Considering that the restoration of SR within 24 hours occurred in 74% of the amiodarone-treated patients and in 89% of the patients treated with propafenone, we plan to include 200 patients to have an 80% chance to demonstrate the superiority of propafenone at p=0.05. ETHICS AND DISSEMINATION: The trial is recruiting patients according to its second protocol version approved by the University Hospital Ethical Board on the 6 October 2017 (No. 1691/16S-IV). The results will be disseminated through peer reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT03029169.

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.

X-ray indices of chest drain malposition after insertion for drainage of pneumothorax in mechanically ventilated critically ill patients.

BACKGROUND: Chest drain (CD) migration in the pleural cavity may result in inadequate drainage of pneumothorax. The aim of this study was to assess several parameters that might help in diagnosing CD migration on chest X-ray (CXR). METHODS: Patients with a CD inserted from the safe triangle with a subsequent supine CXR and CT scan performed less than 24 hours apart were assessed for CD foreshortening, angle of inclination of the CD, and CD tortuosity. CD foreshortening was expressed as a ratio between CD length measured in coronal plane only and CD length inside the pleural cavity measured on CT. The angle of inclination of the CD was measured as the angle between the horizontal line and CD at the pleural space entry on CXR. CD tortuosity was calculated as a ratio between the distance from CD pleural space entry to the tip of the CD and the length of CD from the pleural space entry to its tip on CXR. RESULTS: Altogether 28 patients were included in the study. The median time between the CXR and CT examinations was 5.4 hours (IQR, 3.8-6.9 hours). CD foreshortening was the best clue of a misplaced CD with AUC of 0.93, 100% sensitivity and 88% specificity for a cut-off value of 82%. The angle of CD inclination was greater in patients with misplaced CD with AUC of 0.83, 75% sensitivity and 92% specificity for a cut-off of 50 degrees. The performance of CD tortuosity was poor. CONCLUSIONS: Greater foreshortening of the CD and a steep angle of inclination of the CD above the horizontal at chest entry should raise suspicion of CD migration and mandate further investigation by chest ultrasound to rule out residual pneumothorax occult on CXR.

Neuroinflammation markers and methyl alcohol induced toxic brain damage.

Methyl alcohol intoxication is a global problem with high mortality and long-term visual sequelae and severe brain damage in survivors. The role of neuroinflammation in the mechanisms of methyl alcohol-induced toxic brain damage has not been well studied. We measured the acute concentrations and dynamics of lipoxins LxA4 and LxB4 and the interleukins IL-4, IL-5, IL-9, IL-10, and IL-13 in the serum of patients treated with methyl alcohol poisoning and the follow-up concentrations in survivors two years after discharge from the hospital. A series of acute measurements was performed in 28 hospitalized patients (mean age 54.2 ±â€¯5.2 years, mean observation time 88 ±â€¯20 h) and the follow-up measurements were performed in 36 subjects who survived poisoning (including 12/28 survivors from the acute group). Visual evoked potentials (VEP) and magnetic resonance imaging of the brain (MRI) were performed to detect long-term visual and brain sequelae of intoxication. The acute concentrations of inflammatory mediators were higher than the follow-up concentrations: LxA4, 62.0 ±â€¯6.0 vs. 30.0 ±â€¯5.0 pg/mL; LxB4, 64.0 ±â€¯7.0 vs. 34.0 ±â€¯4.0 pg/mL; IL-4, 29.0 ±â€¯4.0 vs. 15.0 ±â€¯1.0 pg/mL; IL-5, 30.0 ±â€¯4.0 vs. 13.0 ±â€¯1.0 pg/mL; IL-9, 30.0 ±â€¯4.0 vs. 13.0 ±â€¯1.0 pg/mL; IL-10, 38.0 ±â€¯5.0 vs. 16.0 ±â€¯1.0 pg/mL; IL-13, 35.0 ±â€¯4.0 vs. 14.0 ±â€¯1.0 pg/mL (all p < 0.001). The patients with higher follow-up IL-5 concentration had prolonged latency P1 (r = 0.413; p = 0.033) and lower amplitude N1P1 (r = -0.498; p = 0.010) of VEP. The higher follow-up IL-10 concentration was associated with MRI signs of brain necrotic damage (r = 0.533; p = 0.001) and brain hemorrhage (r = 0.396; p = 0.020). Our findings suggest that neuroinflammation plays an important role in the mechanisms of toxic brain damage in acute methyl alcohol intoxication.

Meropenem-induced Valproic Acid Elimination: A Case Report of Clinically Relevant Drug Interaction.

We present two case reports of drug interaction between valproic acid and meropenem. In comparison with expected population-kinetic based serum levels, we observed 90.8 and 93.5% decrease in valproic acid serum levels during concomitant administration with meropenem. If carbapenems need to be administered to valproic acid treated patient, other anticonvulsant addition seems to be the appropriate as most probably the valproic acid dose escalation would not be sufficient to achieve therapeutic serum concentration.

Intermittent versus continuous renal replacement therapy in acute methanol poisoning: comparison of clinical effectiveness in mass poisoning outbreaks.

BACKGROUND: Intermittent hemodialysis (IHD) is the modality of choice in the extracorporeal treatment (ECTR) of acute methanol poisoning. However, the comparative clinical effectiveness of intermittent versus continuous modalities (CRRT) is unknown. During an outbreak of mass methanol poisoning, we therefore studied the effect of IHD versus CRRT on mortality and the prevalence of visual/central nervous system (CNS) sequelae in survivors. METHODS: The study was designed as prospective observational cohort study. Patients hospitalized with a diagnosis of acute methanol poisoning were identified for the study. Exploratory factor analysis and multivariate logistic regression were applied to determine the effect of ECTR modality on the outcome. RESULTS: Data were obtained from 41 patients treated with IHD and 40 patients with CRRT. The follow-up time in survivors was two years. Both groups of patients were comparable by age, time to presentation, laboratory data, clinical features, and other treatment applied. The CRRT group was more acidemic (arterial blood pH 6.96 ± 0.08 vs. 7.17 ± 0.07; p < 0.001) and more severely poisoned (25/40 vs. 9/41 patients with Glasgow Coma Scale (GCS) ≤ 8; p < 0.001). The median intensive care unit length of stay (4 (range 1-16) days vs. 4 (1-22) days; p = 0.703) and the number of patients with complications during the treatment (11/41 vs. 13/40 patients; p = 0.576) did not differ between the groups. The mortality was higher in the CRRT group (15/40 vs. 5/41; p = 0.008). The number of survivors without sequelae of poisoning was higher in the IHD group (23/41 vs. 10/40; p = 0.004). There was a significant association of ECTR modality with both mortality and the number of survivors with visual and CNS sequelae of poisoning, but this association was not present after adjustment for arterial blood pH and GCS on admission (all p > 0.05). CONCLUSIONS: In spite of the faster correction of the acidosis and the quicker removal of the toxic metabolite in intermittent dialysis, we did not find significant differences in the treatment outcomes between the two groups after adjusting for the degree of acidemia and the severity of poisoning on admission. These findings support the strategy of "use what you have" in situations with large outbreaks and limited dialysis capacity.

Failed TAVI in TAVI Implantation: TAVI Dislocation Followed by Ensuing Surgical Graft Resection.

We are presenting a case report of failed valve-in-valve treatment of severe aortic stenosis. A control ultrasonography after TAVI implantation revealed a severe aortic regurgitation of the graft which was subsequently unresolved with postimplantation dilatation. Second TAVI was implanted with cranial dislocation to the aortic root. Patient underwent a CT examination to clarify the TAVI in TAVI position. Patient underwent a surgical resection of TAVI with implantation of biological aortic valve prosthesis. In situations where TAVI treatment fails or is complicated beyond the possibility of endovascular repair, surgical intervention despite its higher risks is the preferred choice.

A rationale for early extracorporeal membrane oxygenation in patients with postinfarction ventricular septal rupture complicated by cardiogenic shock.

AIMS: Ventricular septal rupture (VSR) became a rare mechanical complication of myocardial infarction in the era of percutaneous coronary interventions but is associated with extreme mortality in patients who present with cardiogenic shock (CS). Promising outcomes have been reported with the use of circulatory support allowing haemodynamic stabilization, followed by delayed repair. Therefore, we analysed our experience with an early use of Veno-Arterial Extracorporeal Membrane Oxygenation (V-A ECMO) for postinfarction VSR. METHODS AND RESULTS: We conducted a retrospective search of institutional database for patients presenting with postinfarction VSR from January 2007 to June 2016. Data from 31 consecutive patients (mean age 69.5 ± 9.1 years) who were admitted to hospital were analysed. Seven out of 31 patients with VSR who were in refractory CS received V-A ECMO support preoperatively. ECMO improved end-organ perfusion with decreased lactate levels 24 hours after implantation (7.9 mmol/L vs. 1.6 mmol/L, p = 0.01), normalized arterial pH (7.25 vs. 7.40, p < 0.04), improved mean arterial pressure (64 mmHg vs. 83 mmHg, p < 0.01) and lowered heart rate (115/min vs. 68/min, p < 0.01). Mean duration of ECMO support was 12 days, 5 out of 7 patients underwent surgical repair, 4 were weaned from ECMO, 3 survived 30 days and 2 survived more than 1 year. The most frequent complication (5 patients) and the cause of death (3 patients) was bleeding. CONCLUSIONS: Our experience suggests that early V-A ECMO in patients with VSR and refractory CS might prevent irreversible multiorgan failure by improved end-organ perfusion. Bleeding complications remain an important limitation of this approach.

Cost-effectiveness of hospital treatment and outcomes of acute methanol poisoning during the Czech Republic mass poisoning outbreak.

PURPOSE: During an outbreak of mass methanol poisoning in the Czech Republic in 2012-2014, we compared the total hospital costs and one-year medical costs in the patients treated with different antidotes (fomepizole versus ethanol) and modalities of hemodialysis (intermittent hemodialysis, IHD, versus continuous renal replacement therapy, CRRT). METHODS: Cross-sectional study in 106 patients with confirmed diagnosis treated in 30 ICU settings. For each patient, the following data were analyzed: admission laboratory data, GCS, PSS, ICU length of stay, organ failures, treatment, outcome, and total hospital costs. Of 83 survivors, in 54 (65%) patients the follow-up examination, quality of life measurement with SF36 questionnaire two years after discharge, and one-year medical costs analysis were performed. RESULTS: The median total hospital costs were 7200 (IQR 1500-10,900) euros and the median one-year medical costs were 1447 (IQR 133-1163) euros in the study population. The total hospital costs were higher in the patients treated with fomepizole comparing to ethanol: 12,890 (IQR 6910-16,210) versus 5590 (IQR 1430-6940) euros (p<0.001). The hospital costs in the patients treated with IHD were 5400 (IQR 1520-6910) versus 12,410 (IQR 5380-16,960) euros in the patients with CRRT (p=0.317). The geometric mean ratio for increased hospital costs in the patients treated with fomepizole versus ethanol adjusted for the severity of poisoning was 3.30 (1.70-3.80 CI 95%), p<0.001, and in the patients treated with IHD versus CRRT - 0.70 (0.60-0.99 CI 95%), p=0.047. The patients with visual sequelae had higher total hospital costs than those without sequelae: 10,419 (IQR 2984-14,355) versus 4605 (IQR 1303-4505) euros (p=0.009). The patients with GCS≤13 on admission had higher one-year medical costs as well (p<0.001). No difference was found in physical and mental condition scores in the patients treated with different antidotes and modalities of hemodialysis two years after discharge (both p>0.05). CONCLUSION: The total hospital costs in the patients with acute methanol poisoning were more than three times higher in the patients treated with fomepizole than in the patients treated with ethanol after adjustment for the severity of poisoning. The dialysis modality did not affect the total hospital costs, but the trend to lower costs was present in IHD-group.

Efficiency of acidemia correction on intermittent versus continuous hemodialysis in acute methanol poisoning.

CONTEXT: Acidemia is a marker of prognosis in methanol poisoning, as well as compounding formate-induced cytotoxicity. Prompt correction of acidemia is a key treatment of methanol toxicity and methods to optimize this are poorly defined. OBJECTIVE: We studied the efficiency of acidemia correction by intermittent hemodialysis (IHD) and continuous renal replacement therapy (CRRT) in a mass outbreak of methanol poisoning. METHODS: The study was designed as observational cohort study. The mean time for an increase of 1 mmol/L HCO3-, 0.01 unit arterial blood pH, and the total time for correction of HCO3- were determined in IHD- and CRRT-treated patients. RESULTS: Data were obtained from 18 patients treated with IHD and 13 patients treated with CRRT. At baseline, CRRT group was more acidemic than IHD group (mean arterial pH 6.79 ± 0.10 versus 7.05 ± 0.10; p = 0.001). No association was found between the rate of acidemia correction and age, weight, serum methanol, lactate, formate, and glucose on admission. The time to HCO3- correction correlated with arterial blood pH (r= -0.511; p = 0.003) and creatinine (r = 0.415; p = 0.020). There was association between the time to HCO3- correction and dialysate/effluent and blood flow rates (r= -0.738; p < 0.001 and r= -0.602; p < 0.001, correspondingly). The mean time for HCO3- to increase by 1 mmol/L was 12 ± 2 min for IHD versus 34 ± 8 min for CRRT (p < 0.001), and the mean time for arterial blood pH to increase 0.01 was 7 ± 1 mins for IHD versus 11 ± 4 min for CRRT (p = 0.024). The mean increase in HCO3- was 5.67 ± 0.90 mmol/L/h for IHD versus 2.17 ± 0.74 mmol/L/h for CRRT (p < 0.001). CONCLUSIONS: Our study supports the superiority of IHD over CRRT in terms of the rate of acidemia correction.