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.

Fibrinogenolysis in Venom-Induced Consumption Coagulopathy after Viperidae Snakebites: A Pilot Study.

Envenomations that are caused by Viperidae snakebites are mostly accompanied by venom-induced consumption coagulopathy (VICC) with defibrination. The clinical course of VICC is well described; however, reports about its detailed effects in the hemocoagulation systems of patients are sparse. In this pilot study, we prospectively analyzed the changes in plasma fibrinogen that were caused by the envenomation of six patients by five non-European Viperidae snakes. Western blot analysis was employed and fibrinogen fragments were visualized with the use of specific anti-human fibrinogen antibodies. All of the studied subjects experienced hypo- or afibrinogenemia. The western blot analysis demonstrated fibrinogenolysis of the fibrinogen chains in all of the cases. Fibrinogenolysis was considered to be a predominant cause of defibrination in Crotalus, Echis, and Macrovipera envenomation; while, in the cases of VICC that were caused by Atheris and Calloselasma envenomation, the splitting of the fibrinogen chains was present less significantly.

Splenic Rupture and Massive Hemoperitoneum Due to Coagulopathy after Atheris Viper Snakebite.

Coagulopathy with defibrination is one of symptoms accompanying snakebite envenoming, where life-threatening complications such as massive bleeding and organ hematomas formation can occur. Here, we report a case of hemocoagulation failure due to bite by African Great Lakes bush viper Atheris nitschei with impossibility of specific treatment for absence of antivenom and its life-threatening complication: very rare and unexpected atraumatic splenic rupture with massive hemoperitoneum and necessity of urgent splenectomy.

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.

Diagnostic and prognostic value of presepsin vs. established biomarkers in critically ill patients with sepsis or systemic inflammatory response syndrome.

BACKGROUND: Inflammatory biomarkers may aid to distinguish between systemic inflammatory response syndrome (SIRS) vs. sepsis. We tested the hypotheses that (1) presepsin, a novel biomarker, can distinguish between SIRS and sepsis, and (2) higher presepsin levels will be associated with increased severity of illness and (3) with 28-day mortality, outperforming traditional biomarkers. METHODS: Procalcitonin (PCT), C-reactive protein (CRP), presepsin, and lactate were analyzed in 60 consecutive patients (sepsis and SIRS, n=30 per group) on day 1 (D1) to D3 (onset sepsis, or after cardiac surgery). The systemic organ failure assessment (SOFA) score was determined daily. RESULTS: There was no difference in mortality in sepsis vs. SIRS (12/30 vs. 8/30). Patients with sepsis had higher SOFA score vs. patients with SIRS (11±4 vs. 8±5; p=0.023), higher presepsin (AUC=0.674; p<0.021), PCT (AUC=0.791; p<0.001), CRP (AUC=0.903; p<0.0001), but not lactate (AUC=0.506; p=0.941). Unlike other biomarkers, presepsin did not correlate with SOFA on D1. All biomarkers were associated with mortality on D1: presepsin (AUC=0.734; p=0.0006; best cutoff=1843 pg/mL), PCT (AUC=0.844; p<0.0001), CRP (AUC=0.701; p=0.0048), and lactate (AUC=0.778; p<0.0001). Multiple regression analyses showed independent associations of CRP with diagnosis of sepsis, and CRP and lactate with mortality. Increased neutrophils (p=0.002) and decreased lymphocytes (p=0.007) and monocytes (p=0.046) were also associated with mortality. CONCLUSIONS: Presepsin did not outperform traditional sepsis biomarkers in diagnosing sepsis from SIRS and in prognostication of mortality in critically ill patients. Presepsin may have a limited adjunct value for both diagnosis and an early risk stratification, performing independently of clinical illness severity.

Severe Snakebite Envenoming in Intensive Care.

Snakebites by exotic venomous snakes can cause serious or even life-threatening envenoming. In Europe and North America most victims are breeders, with a few snakebites from wild native American rattlesnakes. The envenomed victims may present in organ and/or system failure with muscle paralysis, respiratory failure, circulatory instability, acute kidney injury, severe coagulation disorder, and local disability - compartment syndrome and necrosis. Best managed by close collaboration between clinical toxicology and intensive care, most severe envenomings are managed primarily by intensive care physicians. Due to the low incidence of severe envenoming, the clinical course and correct management of these cases are not intrinsically familiar to most physicians. This review article summarizes the clinical syndromes caused by severe envenoming and the therapeutic options available in the intensive care setting.

Snakebite Envenoming by Sochurek's Saw-scaled Viper Echis Carinatus Sochureki.

A snake breeder, 47-years-old man, was bitten by the saw-scaled viper (Echis carinatus sochureki). After admission to Toxinology Centre, within 1.5 h, laboratory evaluation showed clotting times prolonged to non-measurable values, afibrinogenaemia, significantly elevated D-dimers, haemolysis and myoglobin elevation. Currently unavailable antivenom was urgently imported and administered within 10 hours. In 24 hours, oligoanuric acute kidney injury (AKI) and mild acute respiratory distress syndrome (ARDS) developed. Despite administration of 10 vials of urgently imported Polyvalent Snake Antivenom Saudi Arabia, the venom-induced consumption coagulopathy (VICC) and AKI persisted. Another ten vials of antivenom were imported from abroad. VICC slowly subsided during the antivenom treatment and disappeared after administration of total 20 vials during 5 day period. No signs of haemorrhage were present during treatment. After resolving VICC, patient was transferred to Department of Nephrology for persisting AKI and requirement for haemodialysis. AKI completely resolved after 20 days. Despite rather timed administration of appropriate antivenom, VICC and AKI developed and the quantity of 20 vials was needed to cease acute symptoms of systemic envenoming. The course illustrates low immunogenicity of the venom haemocoagulation components and thus higher requirements of the antivenom in similar cases.

Envenoming by Crotalid Snake Chinese Moccasin Agkistrodon Acutus Bite - A Case Report.

Although the bites caused by snakes from former Agkistrodon family in the areas of occurrence are not rare and even have certain epidemiologic importance, in case of envenoming by Deinagkistrodon acutus the clinical studies and case reports are very sporadic. This case report describes the envenoming of a private snake breeder bitten by young Chinese moccasin Deinagkistrodon acutus to the thumb of his left hand. He sought for a medical help immediately after snakebite. Patient presented with a local oedema on the affected limb, extending up to the half of the forearm. Laboratory examinations showed serious haemostatic disturbance with defibrination syndrome, immeasurably prolonged clotting times and extreme elevation of D-dimers. No other obvious clinical symptoms were present. Fibrinogen and fresh frozen plasma were administered because the antivenom was not available immediately. The specific antivenom was urgently imported 22 hours after the bite and administered at a dose of two vials three times until laboratory haemocoagulation parameters returned back to physiological values.

Exotic snake bites in the Czech Republic--Epidemiological and clinical aspects during 15-year period (1999-2013).

UNLABELLED: Only one natural venomous snake-the adder viper-lives in the central European region and its bite is usually associated only with mild course of envenoming. Cases of envenoming caused by exotic snakes among their breeders are clinically more important. OBJECTIVE: The aim of this study was to analyze the epidemiological and clinical aspects of registered venomous bites caused by exotic snakes in the Czech Republic over a period of 15 years (1999-2013). MATERIALS AND METHODS: This is an observational case series. Data have been collected retrospectively from a database and medical charts of the Toxinology Center belonging to the General University Hospital in Prague. RESULTS: In total, 87 cases of exotic snakebites caused by 34 venomous snake species were registered during the study period, coming from 18 genera of Elapinae, Viperinae, and Crotalinae subfamilies. In the cohort, 29 patients (33.3%) developed systemic envenoming and 17 (19.5%) were treated with antivenom. Ten cases of envenoming (11.5%) were considered as potentially life threatening. No patient died due to envenoming caused by exotic snake bites during the study period. Four illustrative cases of envenoming (Echis pyramidum, Dendroaspis polylepis, Protobothrops mangshanensis, and Proatheris superciliaris) are described in detail. CONCLUSION: Bites caused by exotic snakes resulted in serious and life-threatening envenomings in some patients. Early transfer to the Center, antivenom administration, and support of failing organ functions contributed to favorable outcome of victims.

Common viper bites in the Czech Republic - epidemiological and clinical aspects during 15 year period (1999-2013).

The aim of this study was to analyse most important epidemiological and clinical aspects of registered snakebites caused by a native common European viper Vipera berus in the Czech Republic over a period of 15 years (1999–2013). Data have been collected retrospectively from a database of the Toxinology Centre belonging to the General University Hospital in Prague. In total, 191 cases of snakebites caused by common viper were registered during the study period. Systemic envenoming occurred in 49 (25.7%) patients, local envenoming without systemic symptoms was recorded in 91 (47.6%) and asymptomatic dry bites were seen in 51 (26.7%) cases, respectively. Twenty-four patients (12.6% of all bites) were treated with administration of antivenom. None of the victims died as a result of snakebite during the observation period. Native viper snakes usually did not cause serious harm to the patients, with the exception of children. Antivenom should be administered in all cases with systemic manifestations, in children even with serious local affection and administered as soon as possible. Envenomed patients should be admitted to the hospital and treated at least under supervision of specialists with experience in snakebite treatment, who can indicate and provide administration of the antivenom.

Bioenergetic gain of citrate anticoagulated continuous hemodiafiltration--a comparison between 2 citrate modalities and unfractionated heparin.

PURPOSE: To determine bioenergetic gain of 2 different citrate anticoagulated continuous hemodiafiltration (CVVHDF) modalities and a heparin modality. MATERIALS AND METHODS: We compared the bio-energetic gain of citrate, glucose and lactate between 29 patients receiving 2.2% acid-citrate-dextrose with calcium-containing lactate-buffered solutions (ACD/Ca(plus)/lactate), 34 on 4% trisodium citrate with calcium-free low-bicarbonate buffered fluids (TSC/Ca(min)/bicarbonate), and 18 on heparin with lactate buffering (Hep/lactate). RESULTS: While delivered CVVHDF dose was about 2000 mL/h, total bioenergetic gain was 262 kJ/h (IQR 230-284) with ACD/Ca(plus)/lactate, 20 kJ/h (8-25) with TSC/Ca(min)/bicarbonate (P < .01) and 60 kJ/h (52-76) with Hep/lactate. Median patient delivery of citrate was 31.2 mmol/h (25-34.7) in ACD/Ca(plus)/lactate versus 14.8 mmol/h (12.4-19.1) in TSC/Ca(min)/bicarbonate groups (P < .01). Median delivery of glucose was 36.8 mmol/h (29.9-43) in ACD/Ca(plus)/lactate, and of lactate 52.5 mmol/h (49.2-59.1) in ACD/Ca(plus)/lactate and 56.1 mmol/h (49.6-64.2) in Hep/lactate groups. The higher energy delivery with ACD/Ca(plus)/lactate was partially due to the higher blood flow used in this modality and the calcium-containing dialysate. CONCLUSIONS: The bioenergetic gain of CVVHDF comes from glucose (in ACD), lactate and citrate. The amount substantially differs between modalities despite a similar CVVHDF dose and is unacceptably high when using ACD with calcium-containing lactate-buffered solutions and a higher blood flow. When calculating nutritional needs, we should account for the energy delivered by CVVHDF.

Protobothrops mangshanensis bite: first clinical report of envenoming and its treatment.

AIM: This case report presents envenoming by the Chinese pit viper Protobothrops mangshanensis (formerly Zhaoermia) and its treatment. METHODS: A 38 year old snake breeder suffered two-fang bites to elbow by a Chinese pit viper Protobothrops mangshanensis resulting in local edema of the affected arm. No other signs of envenoming appeared. On the 5(th) day following the bite a hematoma developed on the other arm which had been mechanically injured 14 days before. Laboratory testing revealed severe coagulopathy with hypofibrinogenemia and immeasurably prolonged coagulation times. RESULTS: As substitution therapy with fibrinogen and fresh frozen plasma was unsuccessful and specific antivenom is not produced, antivenin against some other Asian pit vipers GREEN PIT VIPER ANTIVENIN, Thai Red Cross, Thailand was applied. Three doses of antivenom reversed the course of the hemocoagulation disorder. CONCLUSION: The case confirms the persistence of active venom components affecting coagulation, difficulty in ameliorating the hemocoagulatin disorder caused by snake venom through substitution therapy and the effectiveness of delayed treatment using antivenin. It points out the potential risk of a clinically asymptomatic progress of envenoming by snake venoms containing hemocoagulation acting components, if the hemocoagulation disorder is not investigated and suitably treated. Therapy using the GREEN PIT VIPER ANTIVENIN, Thai Red Cross, Thailand in this case of envenomation by a Protobothrops mangshanensis bite proved to be applicable and the antivenom could be characterised as a paraspecific active.

Quantification of systemic delivery of substrates for intermediate metabolism during citrate anticoagulation of continuous renal replacement therapy.

BACKGROUND: There are limited data on systemic delivery of metabolic substrates during citrate anticoagulation. The direct citrate measurements are usually not available. METHODS: Patients on 2.2% acid-citrate-dextrose (ACD, n = 41) were compared to a control group on unfractionated heparin (n = 17). All were treated on 1.9-m(2) polysulfone filters. Samples were taken from the central venous catheter, ports pre- and post-filter and from effluent. RESULTS: The gain of citrate in CVVH (n = 18) was not different from CVVHDF (n = 23, p = 0.8). Mean gain of citrate was 25.4 ± 6.4 mmol/h. The systemic loads of lactate (p = 0.12) and glucose (p = 0.23) in CVVH were similar to CVVHDF. Mean inputs of lactate and glucose were 62.9 ± 21.1 and 26.6 ± 10.4 mmol/h, respectively. The mean difference between post- and prefilter unmeasured anions (d-UA) correlated with mean difference of citrate concentrations (p < 0.0001, r(2) = 0.66). The estimated caloric load of the citrate modalities was 5,536 ± 1,385 kJ/ 24 h. CONCLUSIONS: ACD might represent a significant load of metabolic substrates, particularly if used with lactate buffer. Systemic delivery of citrate can be predicted using d-UA in the extracorporeal circuit.

Envenoming by the viperid snake Proatheris superciliaris: a case report.

Snake bites caused by viperid snakes of Atheris genus are extremely rare, envenoming of a bite of related viper Proatheris superciliaris was described only once in the literature. The present case study depicts the envenoming of a 57 years old Czech man, a private herpetologist, who was bitten to his finger. He developed painful local reaction, nausea, hematuria, hypertension, chest and lumbar pain. Coagulopathy and thrombocytopenia subsequently developed as well as acute renal failure, hepatic and lung lesion. Intensive care therapy was purely symptomatic and supportive as no antisera exists. Treatment included haemodialysis, substitution of fresh frozen plasma and platelets. Patient completely recovered during 1 month.