Landiolol and Organ Failure in Patients With Septic Shock: The STRESS-L Randomized Clinical Trial.

Importance: Patients with septic shock undergo adrenergic stress, which affects cardiac, immune, inflammatory, and metabolic pathways. ß-Blockade may attenuate the adverse effects of catecholamine exposure and has been associated with reduced mortality. Objectives: To assess the efficacy and safety of landiolol in patients with tachycardia and established septic shock requiring prolonged (>24 hours) vasopressor support. Design, Setting, and Participants: An open-label, multicenter, randomized trial involving 126 adults (≥18 years) with tachycardia (heart rate ≥95/min) and established septic shock treated for at least 24 hours with continuous norepinephrine (≥0.1 µg/kg/min) in 40 UK National Health Service intensive care units. The trial ran from April 2018 to December 2021, with early termination in December 2021 due to a signal of possible harm. Intervention: Sixty-three patients were randomized to receive standard care and 63 to receive landiolol infusion. Main Outcomes and Measures: The primary outcome was the mean Sequential Organ Failure Assessment (SOFA) score from randomization through 14 days. Secondary outcomes included mortality at days 28 and 90 and the number of adverse events in each group. Results: The trial was stopped prematurely on the advice of the independent data monitoring committee because it was unlikely to demonstrate benefit and because of possible harm. Of a planned 340 participants, 126 (37%) were enrolled (mean age, 55.6 years [95% CI, 52.7 to 58.5 years]; 58.7% male). The mean (SD) SOFA score in the landiolol group was 8.8 (3.9) compared with 8.1 (3.2) in the standard care group (mean difference [MD], 0.75 [95% CI, -0.49 to 2.0]; P = .24). Mortality at day 28 after randomization in the landiolol group was 37.1% (23 of 62) and 25.4% (16 of 63) in the standard care group (absolute difference, 11.7% [95% CI, -4.4% to 27.8%]; P = .16). Mortality at day 90 after randomization was 43.5% (27 of 62) in the landiolol group and 28.6% (18 of 63) in the standard care group (absolute difference, 15% [95% CI, -1.7% to 31.6%]; P = .08). There were no differences in the number of patients having at least one adverse event. Conclusion and Relevance: Among patients with septic shock with tachycardia and treated with norepinephrine for more than 24 hours, an infusion of landiolol did not reduce organ failure measured by the SOFA score over 14 days from randomization. These results do not support the use of landiolol for managing tachycardia among patients treated with norepinephrine for established septic shock. Trial Registration: EU Clinical Trials Register Eudra CT: 2017-001785-14; isrctn.org Identifier: ISRCTN12600919.

Burnout Syndrome in UK Intensive Care Unit staff: Data from all three Burnout Syndrome domains and across professional groups, genders and ages.

INTRODUCTION: This is the first comprehensive evaluation of Burnout Syndrome across the UK Intensive Care Unit workforce and in all three Burnout Syndrome domains: Emotional Exhaustion, Depersonalisation and lack of Personal Accomplishment. METHODS: A questionnaire was emailed to UK Intensive Care Society members, incorporating the 22-item Maslach Burnout Inventory Human Services Survey for medical personnel. Burnout Syndrome domain scores were stratified by 'risk'. Associations with gender, profession and age-group were explored. RESULTS: In total, 996 multi-disciplinary responses were analysed. For Emotional Exhaustion, females scored higher and nurses scored higher than doctors. For Depersonalisation, males and younger respondents scored higher. CONCLUSION: Approximately one-third of Intensive Care Unit team-members are at 'high-risk' for Burnout Syndrome, though there are important differences according to domain, gender, age-group and profession. This data may encourage a more nuanced understanding of Burnout Syndrome and more personalised strategies for our heterogeneous workforce.

A practical guide to medical ethics for intensivists.

This series of articles provides a practical guide to dealing with the complex ethical and legal challenges we face in the provision of Intensive Care. They explain the implications of recent legal rulings and cases (such as "Montgomery" and the tragic case of Charlie Gard), and include discussion of clinical scenarios with which we are all familiar. Each article is written by those who are not only experts in their fields, but who also deal with these issues on a day-to-day basis.

Incidence and prognosis of intraabdominal hypertension in a mixed population of critically ill patients: a multiple-center epidemiological study.

OBJECTIVE: Intraabdominal hypertension is associated with significant morbidity and mortality in surgical and trauma patients. The aim of this study was to assess, in a mixed population of critically ill patients, whether intraabdominal pressure at admission was an independent predictor for mortality and to evaluate the effects of intraabdominal hypertension on organ functions. DESIGN: Multiple-center, prospective epidemiologic study. SETTING: Fourteen intensive care units in six countries. PATIENTS: A total of 265 consecutive patients admitted for >24 hrs during the 4-wk study period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Intraabdominal pressure was measured twice daily via the bladder. Data recorded on admission were the patient demographics with Simplified Acute Physiology Score II, Acute Physiology and Chronic Health Evaluation II score, and type of admission; during intensive care stay, Sepsis-Related Organ Failure Assessment score and intraabdominal pressure were measured daily together with fluid balance. Nonsurvivors had a significantly higher mean intraabdominal pressure on admission than survivors: 11.4 +/- 4.8 vs. 9.5 +/- 4.8 mm Hg. Independent predictors for mortality were age (odds ratio, 1.04; 95% confidence interval, 1.01-1.06; p = .003), Acute Physiology and Chronic Health Evaluation II score (odds ratio, 1.1; 95% confidence interval, 1.05-1.15; p < .0001), type of intensive care unit admission (odds ratio, 2.5 medical vs. surgical; 95% confidence interval, 1.24-5.16; p = .01), and the presence of liver dysfunction (odds ratio, 2.5; 95% confidence interval, 1.06-5.8; p = .04). The occurrence of intraabdominal hypertension during the intensive care unit stay was also an independent predictor of mortality (relative risk, 1.85; 95% confidence interval, 1.12-3.06; p = .01). Patients with intraabdominal hypertension at admission had significantly higher Sepsis-Related Organ Failure Assessment scores during the intensive care unit stay than patients without intraabdominal hypertension. CONCLUSIONS: Intraabdominal hypertension on admission was associated with severe organ dysfunction during the intensive care unit stay. The mean intraabdominal pressure on admission was not an independent risk factor for mortality; however, the occurrence of intraabdominal hypertension during the intensive care unit stay was an independent outcome predictor.

Dexmedetomidine infusion for more than 24 hours in critically ill patients: sedative and cardiovascular effects.

OBJECTIVE: To assess the potential of dexmedetomidine for targeted sedation in complex Intensive Care (ICU) patients for >24 h. DESIGN: Prospective, open label, clinical trial. SETTING: Tertiary general ICU. PATIENTS: Twenty critically ill patients, mean APACHE II 23(+/-9). INTERVENTIONS: A continuous infusion of dexmedetomidine, median infusion time 71.5 (35-168) h, starting at 0.4 microg.kg.h without a loading dose and adjusted (0.2-0.7 microg.kg.h) to a target Ramsay Sedation Score (RSS) of 2-4. Rescue midazolam and/or morphine/fentanyl were given as clinically indicated. MEASUREMENTS AND RESULTS: Haemodynamic parameters and RSSs were collected until 24 h after cessation. An RSS 2-5 was achieved in 1,147 (83%) of observations with a reduction in RSS of 6 from 13% in the first 6 h to 3% between 18 h and 24 h. Sixteen patients needed minimal or no additional midazolam, median 4 mg/day (0.5-10) and ten required minimal or no additional analgesia, median 2 mg/day (0.5-4.5), 55 microg/day (14-63) of morphine/fentanyl. RESULTS: A 16% reduction in mean systolic blood pressure (SBP) and 21% reduction in heart rate (HR) occurred over the first 4 h followed by minimal (+/- 10%) changes throughout the infusion. A rise in SBP was observed in two patients. After abrupt cessation, SBP and HR monitored for 24 h rose by 7% and 11%, respectively. CONCLUSIONS: Dexmedetomidine was an effective sedative and analgesic sparing drug in critically ill patients when used without a loading dose for longer than 24 h with predictable falls in blood pressure and HR. There was no evidence of cardiovascular rebound 24 h after abrupt cessation of infusion.

Prevalence of intra-abdominal hypertension in critically ill patients: a multicentre epidemiological study.

OBJECTIVE: Although intra-abdominal hypertension (IAH) can cause dysfunction of several organs and raise mortality, little information is available on the incidence and risk factors for IAH in critically ill patients. This study assessed the prevalence of IAH and its risk factors in a mixed population of intensive care patients. DESIGN: A multicentre, prospective 1-day point-prevalence epidemiological study conducted in 13 ICUs of six countries. INTERVENTIONS: None. PATIENTS: Ninety-seven patients admitted for more than 24 h to one of the ICUs during the 1-day study period. METHODS: Intra-abdominal pressure (IAP) was measured four times (every 6 h) by the bladder pressure method. Data included the demographics, medical or surgical type of admission, SOFA score, etiological factors such as abdominal surgery, haemoperitoneum, abdominal infection, massive fluid resuscitation, and ileus and predisposing conditions such as hypothermia, acidosis, polytransfusion, coagulopathy, sepsis, liver dysfunction, pneumonia and bacteraemia. RESULTS: We enrolled 97 patients, mean age 64+/-15 years, 57 (59%) medical and 40 (41%) surgical admission, SOFA score of 6.5+/-4.0. Mean IAP was 9.8+/-4.7 mmHg. The prevalence of IAH (defined as IAP 12 mmHg or more) was 50.5 and 8.2% had abdominal compartment syndrome (defined as IAP 20 mmHg or more). The only risk factor significantly associated with IAH was the body mass index, while massive fluid resuscitation, renal and coagulation impairment were at limit of significance. CONCLUSION: Although we found a quite high prevalence of IAH, no risk factors were reliably associated with IAH; consequently, to get valid information about IAH, IAP needs to be measured.

A novel method for insertion of post-pyloric feeding tubes at the bedside without endoscopic or fluoroscopic assistance: a prospective study.

OBJECTIVE: To assess a novel method, adapted from already published literature, for bedside placement of nasojejunal feeding tubes using erythromycin, air insufflation of the stomach and continuous ECG guidance. DESIGN AND SETTING: Prospective study in a tertiary teaching hospital. PATIENTS AND PARTICIPANTS: 40 consecutive patients who required enteral nutrition and mechanical ventilation for at least 48 h. INTERVENTIONS: Erythromycin (200 mg) was administered intravenously 30 min prior to the insertion of the feeding tube. The post-pyloric feeding tube was then inserted into the stomach and 500 ml air insufflated. Stomach ECG was performed, and during further insertion of the tube the QRS complex was continuously monitored for a change in polarity, suggesting passage across the midline through the pylorus. At the end of the procedure aspirate was obtained from the feeding tube and checked for alkaline pH. Exact tube position was determined by abdominal radiography. MEASUREMENTS AND RESULTS: In 88% of cases the feeding tubes were post-pyloric, with a median time to insertion of 15 min (range 7-75). No major complications were seen in 52 attempts. Change in QRS polarity had 94% sensitivity in predicting post-pyloric tip placement. Of the 32 alkaline pH aspirates 31 were post-pyloric. CONCLUSIONS: This procedure is safe, effective and could be performed in a short time period within the confines of the intensive care unit without endoscopic assistance.