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.

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.

[Present concept for management of severely injured patients in Trauma Centre Faculty Hospital Královské Vinohrady]. / Aktuální koncepce osetrení závazných poranení v Traumatologickém centru Fakultní nemocnice Královské Vinohrady.

BACKGROUND: The implementation of standardized protocols for management of polytrauma, multiple injuries and complicated monotrauma has led to improvement in trauma care with decrease in posttraumatic morbidity and mortality. The introduction of algorithm "Definitive Surgical Trauma Care" (DSTC) with concept of "damage control" surgery assumed the principal role in care of polytrauma patients. It can be accomplished only in the trauma- centre with implementation of care system for severely injured patients. Analysis of severely injured patients treated in Trauma Centre Faculty Hospital Královské Vinohrady was performed in a retrospective study. METHODS AND RESULTS: 515 injured patients admitted to emergency unit of the Department of anaesthesiology and resuscitation in years 2009-2010 were evaluated. There were 385 men and 130 women. Average age of patients was 45 years. Primary trauma admissions were 482 (83%) victims. There were 248 (48%) polytrauma patients, 158 (31%) with craniocerebral injuries, 76 (15%) with associated injuries and 33 (6 %) injured with monotrauma. ISS > 16 were in 309 injured patients, average rate ISS was 26.5. Trauma care in emergency unit was provided with the team of specialists (general surgeon for visceral traumatology, orthopaedic surgeon for extremities trauma, specialist for intensive care, anaesthesiology and diagnostic radiology). 412 surgical or radio intervention procedures were performed. There were 313 (76%) urgent surgeries and 99 delayed (24%). The most frequent urgent surgery was for fractures of extremities, (36%) and neurotraumas (29%). Acute operations for thoracic and abdominal trauma were performed in 24% of patients. Delayed surgeries were mostly operations of extremities fractures (66%) and maxillofacial injuries (15%). Mortality was 18% (95 patients); being highest in group of patients with Injury Severity Score (ISS) > 40 (65%). CONCLUSIONS: The implementation of trauma care system in severely injured patients brings increased numbers of primary trauma admissions to trauma centres. Polytraumas and craniocerebral injuries were the most frequently admitted patients to emergency unit. Implementation of standardized protocols with interdisciplinary cooperation in trauma management represents improvements of trauma care. Early indication and performance of urgent operations with control of bleeding and prevention of subsequent contamination belongs to principal steps in the management of severely injured patients. Definitive management with reoperation in polytrauma patients can be indicated after the stabilisation. ISS > 40 was connected with high mortality rate (65%).

Frequent intravenous pulses of growth hormone together with glutamine supplementation in prolonged critical illness after multiple trauma: effects on nitrogen balance, insulin resistance, and substrate oxidation.

OBJECTIVES: To estimate the efficacy and metabolic effects of growth hormone substitution as intravenous pulses together with alanyl-glutamine supplementation and tight blood glucose control in prolonged critical illness. DESIGN: Prospective double-blind, randomized trial with open-label control arm. SETTING: Intensive care unit of tertiary level hospital. PATIENTS: Thirty multiple trauma patients (median Injury Severity Score 34). INTERVENTIONS: Patients were randomized, at day 4 after trauma, to receive intravenous alanyl-glutamine supplementation (0.3 g/kg x day(-1) from day 4 until day 17) and intravenous growth hormone (administered days 7-17, full dose 50 microg/kg x day(-1) from day 10 onward) (group 1, n = 10) or alanyl-glutamine and placebo (group 2, n = 10). Group 3 (n = 10) received isocaloric isonitrogenous nutrition (proteins 1.5 g/kg x day(-1)) without alanyl-glutamine. MEASUREMENTS AND MAIN RESULTS: Cumulative nitrogen balance for the whole study period was -97 +/- 38 g of nitrogen for group 1, -193 +/- 50 g of nitrogen for group 2, and -198 +/- 77 g of nitrogen for group 3 (p < .001). This represents a daily saving of 300 g of lean body mass in group 1. Insulin-mediated glucose disposal, during euglycemic clamp, as a measure of insulin sensitivity, significantly worsened between days 4 and 17 in group 1 but improved in groups 2 and 3. Group 1 required significantly more insulin to control blood glucose, resulting in higher insulinemia (approximately 70 mIU in group 1 vs. approximately 25 mIU in groups 2 and 3). Despite this, growth hormone treatment caused an increase in plasma nonesterified fatty acid (approximately 0.5-0.6 mM in group 1 in comparison with approximately 0.2-0.3 mM in groups 2 and 3) but did not influence lipid oxidation. There were no differences in morbidity, mortality, or 6-month outcome among the groups. CONCLUSIONS: Treatment with frequent intravenous pulses of low-dose growth hormone together with alanyl-glutamine supplementation improves nitrogen economy in patients with prolonged critical illness after multiple trauma but worsens insulin sensitivity. Tight blood glucose control is possible but requires higher doses of insulin.

Frequent intravenous pulses of growth hormone together with alanylglutamine supplementation in prolonged critical illness after multiple trauma: effects on glucose control, plasma IGF-I and glutamine.

OBJECTIVE: We aim to demonstrate that low dose growth hormone (GH) administered in i.v. pulses every 3h is able to normalize IGF-I levels in subjects with prolonged critical illness, after multiple trauma. We also ask whether it is possible to control glycaemia during such a treatment and how alanylglutamine (AG) supplementation influences plasma glutamine concentration. METHODS: We used a prospective double-blind (group 1 vs. 2), randomized trial with an open-label control arm (group 3). Thirty multiple trauma patients (median age: 36, 42, 46 years) were randomized on day 4 after trauma to receive (group 1, n=10) i.v. AG supplementation (0.3 g/kg day from day 4 till 17) and i.v. GH (0.05 mg/kg day divided into 8 boluses, maximum dose at 3 AM, administered on days 7-17) or AG and placebo (group 2, n=10). Group 3 (n=10) received isocaloric isonitrogenous (proteins 1.5 g/kg day) nutrition without AG. Glycaemia was controlled by i.v. insulin infusion according to a routine protocol. RESULTS: GH treatment caused an increase of IGF-I (from median 169 on day 4 to 493 ng/ml on day 17), IGFBP-3 (from 2.4 to 3.2 microg/ml) and a fall in IGFBP-1 (from 11.5 to 3.1 microg/ml), whilst in both groups 2 and 3 these indices remained unchanged. At the end of the study (day 17) IGF-I and IGFBP-1 differed significantly among groups (p=0.008 resp. p=0.010, Kruskal-Wallis). Plasma glutamine remained below the normal range through the study in all groups (median: 0.18-0.30 mM), but had a tendency to rise in group 2 in contrast with a fall in groups 1 and 3 (NS). Group 1 required more insulin (p<0.01) than did the control group but median glycaemia was only 0.4-0.5 mM higher in group 1 (6.5 mM) than in groups 2 and 3 (6.1 resp. 6.0 mM). CONCLUSIONS: GH (0.05 g/kg day) administered in i.v. pulses is able to normalize IGF-I levels in subjects with prolonged critical illness after trauma. During this treatment, the standard dose of AG prevents worsening of plasma glutamine deficiency and glucose control is possible using routine algorithms, but it requires higher insulin doses.

Parenterally administered dipeptide alanyl-glutamine prevents worsening of insulin sensitivity in multiple-trauma patients.

BACKGROUND: Dipeptide alanyl-glutamine is a commonly used substrate in major trauma patients. Its importance and effects are widely discussed; as yet, it has not been elucidated whether its administration influences glucose homeostasis. OBJECTIVE: We studied the effect of alanyl-glutamine administration on insulin resistance. DESIGN: Prospective, randomized, controlled trial. SETTING: Intensive care unit of a tertiary level hospital. PATIENTS: Multiple-trauma patients. INTERVENTIONS: Patients were randomized into two groups and assigned to receive parenterally an equal dose of amino acids either with alanyl-glutamine in the dose of 0.4 g x kg body weight(-1) x 24 hrs(-1) (group AG) or without alanyl-glutamine (control group C). This regimen started 24 hrs after injury and continued for 7 days. To assess insulin sensitivity, we performed an euglycemic clamp on day 4 and day 8 after injury. MEASUREMENTS AND MAIN RESULTS: We randomized 40 patients, 20 into each group. At day 4, insulin-mediated glucose disposal was higher in group AG (2.4 +/- 0.7 mg x kg(-1) x min(-1) glucose), with significant difference from group C (1.9 +/- 0.6 mg x kg(-1) x min(-1), p = .044). At day 8, glucose disposal was higher in group AG (2.2 +/- 0.7 mg x kg(-1) x min(-1) glucose), with significant difference in comparison with group C (1.2 +/- 0.6, p < .001). Diminution of the main glucose homeostasis variables in group C between days 4 and 8 of the study was statistically significant (p < .001); however, differences in these variables in group AG were without statistical significance. CONCLUSIONS: Parenteral supplementation of alanyl-glutamine dipeptide was associated with better insulin sensitivity in multiple-trauma patients.