Faculty Bibliography

Importance/UNASSIGNED:Abnormal peripheral perfusion after septic shock resuscitation has been associated with organ dysfunction and mortality. The potential role of the clinical assessment of peripheral perfusion as a target during resuscitation in early septic shock has not been established. Objective/UNASSIGNED:To determine if a peripheral perfusion-targeted resuscitation during early septic shock in adults is more effective than a lactate level-targeted resuscitation for reducing mortality. Design, Setting, and Participants/UNASSIGNED:Multicenter, randomized trial conducted at 28 intensive care units in 5 countries. Four-hundred twenty-four patients with septic shock were included between March 2017 and March 2018. The last date of follow-up was June 12, 2018. Interventions/UNASSIGNED:Patients were randomized to a step-by-step resuscitation protocol aimed at either normalizing capillary refill time (n = 212) or normalizing or decreasing lactate levels at rates greater than 20% per 2 hours (n = 212), during an 8-hour intervention period. Main Outcomes and Measures/UNASSIGNED:The primary outcome was all-cause mortality at 28 days. Secondary outcomes were organ dysfunction at 72 hours after randomization, as assessed by Sequential Organ Failure Assessment (SOFA) score (range, 0 [best] to 24 [worst]); death within 90 days; mechanical ventilation-, renal replacement therapy-, and vasopressor-free days within 28 days; intensive care unit and hospital length of stay. Results/UNASSIGNED:Among 424 patients randomized (mean age, 63 years; 226 [53%] women), 416 (98%) completed the trial. By day 28, 74 patients (34.9%) in the peripheral perfusion group and 92 patients (43.4%) in the lactate group had died (hazard ratio, 0.75 [95% CI, 0.55 to 1.02]; P = .06; risk difference, -8.5% [95% CI, -18.2% to 1.2%]). Peripheral perfusion-targeted resuscitation was associated with less organ dysfunction at 72 hours (mean SOFA score, 5.6 [SD, 4.3] vs 6.6 [SD, 4.7]; mean difference, -1.00 [95% CI, -1.97 to -0.02]; P = .045). There were no significant differences in the other 6 secondary outcomes. No protocol-related serious adverse reactions were confirmed. Conclusions and Relevance/UNASSIGNED:Among patients with septic shock, a resuscitation strategy targeting normalization of capillary refill time, compared with a strategy targeting serum lactate levels, did not reduce all-cause 28-day mortality. Trial Registration/UNASSIGNED:ClinicalTrials.gov Identifier: NCT03078712.

Sepsis is one of the main reasons for intensive care unit admission and is responsible for high morbidity and mortality. The usual hemodynamic targets for resuscitation of patients with septic shock use macro-hemodynamic parameters (hearth rate, mean arterial pressure, central venous pressure). However, persistent alterations of microcirculatory blood flow despite restoration of macro-hemodynamic parameters can lead to organ failure. This dissociation between macro- and microcirculatory compartments brings a need to assess end organs tissue perfusion in patients with septic shock. Traditional markers of tissue perfusion may not be readily available (lactate) or may take time to assess (urine output). The skin, an easily accessible organ, allows clinicians to quickly evaluate the peripheral tissue perfusion with noninvasive bedside parameters such as the skin temperatures gradient, the capillary refill time, the extent of mottling and the peripheral perfusion index.

BACKGROUND:Vasopressors are commonly applied to restore and maintain blood pressure in patients with sepsis. We aimed to evaluate the current practice and therapeutic goals regarding vasopressor use in septic shock as a basis for future studies and to provide some recommendations on their use. METHODS:From November 2016 to April 2017, an anonymous web-based survey on the use of vasoactive drugs was accessible to members of the European Society of Intensive Care Medicine (ESICM). A total of 17 questions focused on the profile of respondents, triggering factors, first choice agent, dosing, timing, targets, additional treatments, and effects of vasopressors. We investigated whether the answers complied with current guidelines. In addition, a group of 34 international ESICM experts was asked to formulate recommendations for the use of vasopressors based on 6 questions with sub-questions (total 14). RESULTS:A total of 839 physicians from 82 countries (65% main specialty/activity intensive care) responded. The main trigger for vasopressor use was an insufficient mean arterial pressure (MAP) response to initial fluid resuscitation (83%). The first-line vasopressor was norepinephrine (97%), targeting predominantly a MAP > 60-65 mmHg (70%), with higher targets in patients with chronic arterial hypertension (79%). The experts agreed on 10 recommendations, 9 of which were based on unanimous or strong (≥ 80%) agreement. They recommended not to delay vasopressor treatment until fluid resuscitation is completed but rather to start with norepinephrine early to achieve a target MAP of ≥ 65 mmHg. CONCLUSION/CONCLUSIONS:Reported vasopressor use in septic shock is compliant with contemporary guidelines. Future studies should focus on individualized treatment targets including earlier use of vasopressors.

The original article can be found online.

PURPOSE/OBJECTIVE:Changes of lactate concentration over time were reported to be associated with survival in septic patients. We aimed to evaluate delta-lactate (ΔLac) 24 h after admission (Δ24Lac) to an intensive care unit (ICU) in critically ill patients for short- and long-term prognostic relevance. METHODS:In total, 26,285 lactate measurements of 2191 patients admitted to a German ICU were analyzed. Inclusion criterion was a lactate concentration at admission above 2.0 mmol/L. Maximum lactate concentrations of day 1 and day 2 were used to calculate Δ24Lac. Follow-up of patients was performed retrospectively. Association of Δ24Lac and both in-hospital and long-term mortality were investigated. An optimal cut-off was calculated by means of the Youden index. RESULTS:Patients with lower Δ24Lac were of similar age, but clinically sicker. As continuous variable, higher Δ24Lac was associated with decreased in-hospital mortality (per 1% Δ24Lac; HR 0.987 95%CI 0.985-0.990; p < 0.001) and an optimal Δ24Lac cut-off was calculated at 19%. Δ24Lac ≤ 19% was associated with both increased in-hospital (15% vs 43%; OR 4.11; 95%CI 3.23-5.21; p < 0.001) and long-term mortality (HR 1.54 95%CI 1.28-1.87; p < 0.001), even after correction for APACHE II, need for catecholamines and intubation. We matched 256 patients with Δ24Lac ≤ 19% to case-controls > 19% corrected for APACHE II scores, baseline lactate level and sex: Δ24Lac ≤ 19% remained associated with lower in-hospital and long-term survival. CONCLUSIONS:Lower Δ24Lac was robustly associated with adverse outcome in critically ill patients, even after correction for confounders. Δ24Lac might constitute an independent, easily available and important parameter for risk stratification in the critically ill.

OBJECTIVES/OBJECTIVE:Implementation of delirium guidelines at ICUs is suboptimal. The aim was to evaluate the impact of a tailored multifaceted implementation program of ICU delirium guidelines on processes of care and clinical outcomes and draw lessons regarding guideline implementation. DESIGN/METHODS:A prospective multicenter, pre-post, intervention study. SETTING/METHODS:ICUs in one university hospital and five community hospitals. PATIENTS/METHODS:Consecutive medical and surgical critically ill patients were enrolled between April 1, 2012, and February 1, 2015. INTERVENTIONS/METHODS:Multifaceted, three-phase (baseline, delirium screening, and guideline) implementation program of delirium guidelines in adult ICUs. MEASUREMENTS AND MAIN RESULTS/RESULTS:The primary outcome was adherence changes to delirium guidelines recommendations, based on the Pain, Agitation and Delirium guidelines. Secondary outcomes were brain dysfunction (delirium or coma), length of ICU stay, and hospital mortality. A total of 3,930 patients were included. Improvements after the implementation pertained to delirium screening (from 35% to 96%; p < 0.001), use of benzodiazepines for continuous sedation (from 36% to 17%; p < 0.001), light sedation of ventilated patients (from 55% to 61%; p < 0.001), physiotherapy (from 21% to 48%; p < 0.001), and early mobilization (from 10% to 19%; p < 0.001). Brain dysfunction improved: the mean delirium duration decreased from 5.6 to 3.3 days (-2.2 d; 95% CI, -3.2 to -1.3; p < 0.001), and coma days decreased from 14% to 9% (risk ratio, 0.5; 95% CI, 0.4-0.6; p < 0.001). Other clinical outcome measures, such as length of mechanical ventilation, length of ICU stay, and hospital mortality, did not change. CONCLUSIONS:This large pre-post implementation study of delirium-oriented measures based on the 2013 Pain, Agitation, and Delirium guidelines showed improved health professionals' adherence to delirium guidelines and reduced brain dysfunction. Our findings provide empirical support for the differential efficacy of the guideline bundle elements in a real-life setting and provide lessons for optimization of guideline implementation programs.

An international team of experts in the field of fluid resuscitation was invited by the ESICM to form a task force to systematically review the evidence concerning fluid administration using basic monitoring. The work included a particular emphasis on pre-ICU hospital settings and resource-limited settings. The work focused on four main questions: (1) What is the role of clinical assessment to guide fluid resuscitation in shock? (2) What basic monitoring is required to perform and interpret a fluid challenge? (3) What defines a fluid challenge in terms of fluid type, ranges of volume, and rate of administration? (4) What are the safety endpoints during a fluid challenge? The expert panel found insufficient evidence to provide recommendations according to the GRADE system, and was only able to make recommendations for basic interventions, based on the available evidence and expert opinion. The panel identified significant gaps in the scientific evidence on fluid administration outside the ICU (excluding the operating theater). Globally, scientific communities and health care systems should address these critical gaps in evidence through research on how basic fluid administration in resource-rich and resource-limited settings can be improved for the benefit of patients and societies worldwide.