The current state of intensive care unit discharge practices - Results of an international survey study.

Background: Increasing pressure on limited intensive care capacities often requires a subjective assessment of a patient's discharge readiness in the absence of established Admission, Discharge, and Transfer (ADT) guidelines. To avoid suboptimal care transitions, it is important to define clear guidelines for the admission and discharge of intensive care patients and to optimize transfer processes between the intensive care unit (ICU) and lower care levels. To achieve these goals, structured insights into usual ICU discharge and transfer practices are essential. This study aimed to generate these insights by focusing on involved stakeholders, established processes, discharge criteria and tools, relevant performance metrics, and current barriers to a timely and safe discharge. Method: In 2022, a structured, web-based, anonymous cross-sectional survey was conducted, aimed at practicing ICU physicians, nurses, and bed coordinators. The survey consisted of 29 questions (open, closed, multiple choice, and scales) that were divided into thematic blocks. The study was supported by several national and international societies for intensive care medicine and nursing. Results: A total of 219 participants from 40 countries (105 from Germany) participated in the survey. An overload of acute care resources with ~90% capacity utilization in the ICU and the general ward (GW) leads to not only premature but also delayed patient transfers due to a lack of available ward and intermediate care (IMC) beds. After multidisciplinary rounds within the intensive care team, the ICU clinician on duty usually makes the final transfer decision, while one-third of the panel coordinates discharge decisions across departmental boundaries. By the end of the COVID-19 pandemic, half of the hospitals had implemented ADT policies. Among these hospitals, nearly one-third of the hospitals had specific transfer criteria established, consisting primarily of vital signs and laboratory data, patient status and autonomy, and organization-specific criteria. Liaison nurses were less common but were ranked right after the required IMC capacities to bridge the care gap between the ICU and normal wards. In this study, 80% of the participants suggested that transfer planning would be easier if there was good transparency regarding the capacity utilization of lower care levels, a standardized transfer process, and improved interdisciplinary communication. Conclusion: To improve care transitions, transfer processes should be managed proactively across departments, and efforts should be made to identify and address care gaps.

Anaerobic Lactate Production Is Associated With Decreased Microcirculatory Blood Flow and Decreased Mitochondrial Respiration Following Cardiovascular Surgery With Cardiopulmonary Bypass.

OBJECTIVES: Quantify the relationship between perioperative anaerobic lactate production, microcirculatory blood flow, and mitochondrial respiration in patients after cardiovascular surgery with cardiopulmonary bypass. DESIGN: Serial measurements of lactate-pyruvate ratio (LPR), microcirculatory blood flow, plasma tricarboxylic acid cycle cycle intermediates, and mitochondrial respiration were compared between patients with a normal peak lactate (≤ 2 mmol/L) and a high peak lactate (≥ 4 mmol/L) in the first 6 hours after surgery. Regression analysis was performed to quantify the relationship between clinically relevant hemodynamic variables, lactate, LPR, and microcirculatory blood flow. SETTING: This was a single-center, prospective observational study conducted in an academic cardiovascular ICU. PATIENTS: One hundred thirty-two patients undergoing elective cardiovascular surgery with cardiopulmonary bypass. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients with a high postoperative lactate were found to have a higher LPR compared with patients with a normal postoperative lactate (14.4 ± 2.5 vs. 11.7 ± 3.4; p = 0.005). Linear regression analysis found a significant, negative relationship between LPR and microcirculatory flow index (r = -0.225; ß = -0.037; p = 0.001 and proportion of perfused vessels: r = -0.17; ß = -0.468; p = 0.009). There was not a significant relationship between absolute plasma lactate and microcirculation variables. Last, mitochondrial complex I and complex II oxidative phosphorylation were reduced in patients with high postoperative lactate levels compared with patients with normal lactate (22.6 ± 6.2 vs. 14.5 ± 7.4 pmol O2/s/106 cells; p = 0.002). CONCLUSIONS: Increased anaerobic lactate production, estimated by LPR, has a negative relationship with microcirculatory blood flow after cardiovascular surgery. This relationship does not persist when measuring lactate alone. In addition, decreased mitochondrial respiration is associated with increased lactate after cardiovascular surgery. These findings suggest that high lactate levels after cardiovascular surgery, even in the setting of normal hemodynamics, are not simply a type B phenomenon as previously suggested.

Fluid Responsiveness Is Associated with Successful Weaning after Liver Transplant Surgery.

A positive fluid balance may evolve to fluid overload and associate with organ dysfunctions, weaning difficulties, and increased mortality in ICU patients. We explored whether individualized fluid management, assessing fluid responsiveness via a passive leg-raising maneuver (PLR) before a spontaneous breathing trial (SBT), is associated with less extubation failure in ventilated patients with a high fluid balance admitted to the ICU after liver transplantation (LT). We recruited 15 LT patients in 2023. Their postoperative fluid balance was +4476 {3697, 5722} mL. PLR maneuvers were conducted upon ICU admission (T1) and pre SBT (T2). Cardiac index (CI) changes were recorded before and after each SBT (T3). Seven patients were fluid-responsive at T1, and twelve were responsive at T2. No significant differences occurred in hemodynamic, respiratory, and perfusion parameters between the fluid-responsive and fluid-unresponsive patients at any time. Fluid-responsive patients at T1 and T2 increased their CI during SBT from 3.1 {2.8, 3.7} to 3.7 {3.4, 4.1} mL/min/m2 (p = 0.045). All fluid-responsive patients at T2 were extubated after the SBTs and consolidated extubation. Two out of three of the fluid-unresponsive patients experienced weaning difficulties. We concluded that fluid-responsive patients post LT may start weaning earlier and achieve successful extubation despite a high postoperative fluid balance. This highlights the profound impact of personalized assessments of cardiovascular state on critical surgical patients.

Capillary refill time response to a fluid challenge or a vasopressor test: an observational, proof-of-concept study.

BACKGROUND: Several studies have validated capillary refill time (CRT) as a marker of tissue hypoperfusion, and recent guidelines recommend CRT monitoring during septic shock resuscitation. Therefore, it is relevant to further explore its kinetics of response to short-term hemodynamic interventions with fluids or vasopressors. A couple of previous studies explored the impact of a fluid bolus on CRT, but little is known about the impact of norepinephrine on CRT when aiming at a higher mean arterial pressure (MAP) target in septic shock. We designed this observational study to further evaluate the effect of a fluid challenge (FC) and a vasopressor test (VPT) on CRT in septic shock patients with abnormal CRT after initial resuscitation. Our purpose was to determine the effects of a FC in fluid-responsive patients, and of a VPT aimed at a higher MAP target in chronically hypertensive fluid-unresponsive patients on the direction and magnitude of CRT response. METHODS: Thirty-four septic shock patients were included. Fluid responsiveness was assessed at baseline, and a FC (500 ml/30 mins) was administered in 9 fluid-responsive patients. A VPT was performed in 25 patients by increasing norepinephrine dose to reach a MAP to 80-85 mmHg for 30 min. Patients shared a multimodal perfusion and hemodynamic monitoring protocol with assessments at at least two time-points (baseline, and at the end of interventions). RESULTS: CRT decreased significantly with both tests (from 5 [3.5-7.6] to 4 [2.4-5.1] sec, p = 0.008 after the FC; and from 4.0 [3.3-5.6] to 3 [2.6 -5] sec, p = 0.03 after the VPT. A CRT-response was observed in 7/9 patients after the FC, and in 14/25 pts after the VPT, but CRT deteriorated in 4 patients on this latter group, all of them receiving a concomitant low-dose vasopressin. CONCLUSIONS: Our findings support that fluid boluses may improve CRT or produce neutral effects in fluid-responsive septic shock patients with persistent hypoperfusion. Conversely, raising NE doses to target a higher MAP in previously hypertensive patients elicits a more heterogeneous response, improving CRT in the majority, but deteriorating skin perfusion in some patients, a fact that deserves further research.

Serial daily lactate levels association with 30-day outcome in cardiogenic shock patients treated with VA-ECMO: a post-hoc analysis of the HYPO-ECMO study.

BACKGROUND: Reliable predictors of outcomes in venoarterial extracorporeal membrane oxygenation (VA-ECMO) therapy are limited. While elevated lactate levels over time have been linked to outcomes in cardiogenic shock (CS), their significance in VA-ECMO-treated patients remains inconclusive. METHODS: We conducted a post hoc analysis of data from the HYPO-ECMO trial, which compared normothermia to moderate hypothermia in CS patients supported by VA-ECMO. We examined daily lactate levels collected over a week to assess their correlation with 30-day mortality. RESULTS: Among the 318 out of 334 patients (95%) with baseline lactate measurements, 66 had normal levels (< 2.2 mmol/l, 21%). No difference was found in lactate course between moderate hypothermia and normothermia groups. Lactate levels were consistently higher in non-survivors at each time point (p = 0.0002). Baseline hyperlactatemia was associated with an increased risk of death (Hazard Ratio [HR]: 1.85 (1.12-3.05), p = 0.016). When considering all time points, lactate levels during the ICU stay were significantly and gradually associated with a higher risk of death (p < 0.0001). In the overall population, a decrease in lactate levels was not linked to 30-day mortality. However, patients with baseline hyperlactatemia exhibited a more significant decrease in lactate levels from day one to seven (p < 0.0001). In this group, survivors had a significantly greater decrease in lactate levels at day 1 compared to non-survivors (63% (48-77) versus 57% (21-75), p = 0.026). Patients experiencing a secondary increase in lactate (24%) had a worse prognosis (Hazard Ratio: 1.78 (1.21-2.61), p = 0.004), regardless of both baseline lactate levels and the occurrence of severe ischemic adverse events (intestinal and/or limb ischemia). CONCLUSIONS: The consistent and significant association between lactate levels, whether assessed at baseline or during ICU treatment, and the risk of mortality underscores the pivotal prognostic relevance of lactate levels in patients with CS undergoing VA-ECMO therapy. The study findings provide some novel insights, regarding the trend profile and the relevance of a second peak during the 7 day period after ECMO start. Trial Registration identifier NCT02754193 registered on 2016-04-12.

Relationship Between the Mixed Venous-to-Arterial Carbon Dioxide Gradient and Cardiac Index in Acute Pulmonary Embolism.

BACKGROUND: Among patients with acute pulmonary embolism (PE) undergoing mechanical thrombectomy, the cardiac index (CI) is frequently reduced even among those without clinically apparent shock. The purpose of this study was to describe the mixed venous-to-arterial carbon dioxide gradient (CO2 gap), a surrogate of perfusion adequacy, among patients with acute PE undergoing mechanical thrombectomy. METHODS: This was a single-center retrospective study of consecutive patients with PE undergoing mechanical thrombectomy and simultaneous pulmonary artery catheterization over a 3-year period. RESULTS: Of 107 patients, 97 had simultaneous mixed venous and arterial blood gas measurements available. The CO2 gap was elevated (>6 mmHg) in 51% of the cohort and in 49% of patients with intermediate-risk PE. A reduced CI (≤2.2 L/min/m2) was associated with an increased odds (OR = 7.9; 95% CI 3.49-18.1, p < 0.001) for an elevated CO2 gap. There was an inverse relationship between CI and CO2 gap. For every 1 L/min/m2 decrease in the CI, the CO2 gap increased by 1.3 mmHg (p = 0.001). Among patients with an elevated baseline CO2 gap >6 mmHg, thrombectomy improved CO2 gap, CI, and mixed venous oxygen saturation. When the CO2 gap was dichotomized above and below 6, there was no difference in in-hospital mortality (9% vs. 0%; p = 0.10, HR: 1.24; 95% CI: 0.97-1.60; P = 0.085). CONCLUSIONS: Among patients with acute PE undergoing mechanical thrombectomy, the CO2 gap is abnormal in nearly 50% of patients and inversely related to CI. Further studies should examine the relationship between markers of perfusion and outcomes in this population to refine risk stratification.

Coexistence of a fluid responsive state and venous congestion signals in critically ill patients: a multicenter observational proof-of-concept study.

BACKGROUND: Current recommendations support guiding fluid resuscitation through the assessment of fluid responsiveness. Recently, the concept of fluid tolerance and the prevention of venous congestion (VC) have emerged as relevant aspects to be considered to avoid potentially deleterious side effects of fluid resuscitation. However, there is paucity of data on the relationship of fluid responsiveness and VC. This study aims to compare the prevalence of venous congestion in fluid responsive and fluid unresponsive critically ill patients after intensive care (ICU) admission. METHODS: Multicenter, prospective cross-sectional observational study conducted in three medical-surgical ICUs in Chile. Consecutive mechanically ventilated patients that required vasopressors and admitted < 24 h to ICU were included between November 2022 and June 2023. Patients were assessed simultaneously for fluid responsiveness and VC at a single timepoint. Fluid responsiveness status, VC signals such as central venous pressure, estimation of left ventricular filling pressures, lung, and abdominal ultrasound congestion indexes and relevant clinical data were collected. RESULTS: Ninety patients were included. Median age was 63 [45-71] years old, and median SOFA score was 9 [7-11]. Thirty-eight percent of the patients were fluid responsive (FR+), while 62% were fluid unresponsive (FR-). The most prevalent diagnosis was sepsis (41%) followed by respiratory failure (22%). The prevalence of at least one VC signal was not significantly different between FR+ and FR- groups (53% vs. 57%, p = 0.69), as well as the proportion of patients with 2 or 3 VC signals (15% vs. 21%, p = 0.4). We found no association between fluid balance, CRT status, or diagnostic group and the presence of VC signals. CONCLUSIONS: Venous congestion signals were prevalent in both fluid responsive and unresponsive critically ill patients. The presence of venous congestion was not associated with fluid balance or diagnostic group. Further studies should assess the clinical relevance of these results and their potential impact on resuscitation and monitoring practices.

Association of tissue oxygen saturation levels with skeletal muscle injury in the critically ill.

This study aimed to investigate the association between the level of tissue oxygen saturation (StO2) and quadriceps/skeletal muscle dysfunction, measured using the Medical Research Council (MRC) scale and ultrasonography, in critically ill patients. Thirty-four patients hospitalized at the Critical Care Medicine Center of Kindai University Hospital, between January 2022 and March 2023, were enrolled in this study. The StO2 of the quadriceps muscle was measured via near-infrared spectroscopy. Muscle atrophy was measured by the thickness, cross-sectional area (CSA), and echo intensity of the rectus femoris (RF). These values were evaluated every alternate day until 13 days after admission or until discharge, whichever occurred first. Muscle weakness was assessed using the sum score of the MRC scale (MRC-SS), with the patient sitting at bedside. The mean age of the patients was 67.3 ± 15.3 years, and 20 (59%) were men. Seven patients (21%) were admitted for trauma, and 27 (79%) were admitted for medical emergencies or others. The mean score for the MRC-SS was 51.0 ± 7.9 points. RF thickness and CSA significantly decreased after day 7 (p < 0.05). There were no significant changes in StO2 levels during hospitalization. However, there were positive correlations between the nadir StO2 during hospitalization and MRC-SS, and changes in RF thickness and CSA at discharge (r = 0.41, p = 0.03; r = 0.37, p = 0.03; and r = 0.35, p = 0.05, respectively). StO2 in the quadriceps muscle may be useful for predicting muscle atrophy and dysfunction in patients with critical illnesses.

Noncanonical-NF-κB activation and DDX3 inhibition reduces the HIV-1 reservoir by elimination of latently infected cells ex-vivo.

IMPORTANCE: HIV-1 continues to be a major global health challenge. Current HIV-1 treatments are effective but need lifelong adherence. An HIV-1 cure should eliminate the latent viral reservoir that persists in people living with HIV-1. Different methods have been investigated that focus on reactivation and subsequent elimination of the HIV-1 reservoir, and it is becoming clear that a combination of compounds with different mechanisms of actions might be more effective. Here, we target two host factors, inhibitor of apoptosis proteins that control apoptosis and the DEAD-box helicase DDX3, facilitating HIV mRNA transport/translation. We show that targeting of these host factors with SMAC mimetics and DDX3 inhibitors induce reversal of viral latency and eliminate HIV-1-infected cells in vitro and ex vivo.

Red Blood Cell Transfusion in the Intensive Care Unit.

Importance: Red blood cell (RBC) transfusion is common among patients admitted to the intensive care unit (ICU). Despite multiple randomized clinical trials of hemoglobin (Hb) thresholds for transfusion, little is known about how these thresholds are incorporated into current practice. Objective: To evaluate and describe ICU RBC transfusion practices worldwide. Design, Setting, and Participants: International, prospective, cohort study that involved 3643 adult patients from 233 ICUs in 30 countries on 6 continents from March 2019 to October 2022 with data collection in prespecified weeks. Exposure: ICU stay. Main Outcomes and Measures: The primary outcome was the occurrence of RBC transfusion during ICU stay. Additional outcomes included the indication(s) for RBC transfusion (consisting of clinical reasons and physiological triggers), the stated Hb threshold and actual measured Hb values before and after an RBC transfusion, and the number of units transfused. Results: Among 3908 potentially eligible patients, 3643 were included across 233 ICUs (median of 11 patients per ICU [IQR, 5-20]) in 30 countries on 6 continents. Among the participants, the mean (SD) age was 61 (16) years, 62% were male (2267/3643), and the median Sequential Organ Failure Assessment score was 3.2 (IQR, 1.5-6.0). A total of 894 patients (25%) received 1 or more RBC transfusions during their ICU stay, with a median total of 2 units per patient (IQR, 1-4). The proportion of patients who received a transfusion ranged from 0% to 100% across centers, from 0% to 80% across countries, and from 19% to 45% across continents. Among the patients who received a transfusion, a total of 1727 RBC transfusions were administered, wherein the most common clinical indications were low Hb value (n = 1412 [81.8%]; mean [SD] lowest Hb before transfusion, 7.4 [1.2] g/dL), active bleeding (n = 479; 27.7%), and hemodynamic instability (n = 406 [23.5%]). Among the events with a stated physiological trigger, the most frequently stated triggers were hypotension (n = 728 [42.2%]), tachycardia (n = 474 [27.4%]), and increased lactate levels (n = 308 [17.8%]). The median lowest Hb level on days with an RBC transfusion ranged from 5.2 g/dL to 13.1 g/dL across centers, from 5.3 g/dL to 9.1 g/dL across countries, and from 7.2 g/dL to 8.7 g/dL across continents. Approximately 84% of ICUs administered transfusions to patients at a median Hb level greater than 7 g/dL. Conclusions and Relevance: RBC transfusion was common in patients admitted to ICUs worldwide between 2019 and 2022, with high variability across centers in transfusion practices.

Low postoperative perfused vessel density is associated with increased soluble endothelial cell adhesion molecules during circulatory shock after cardiac surgery.

INTRODUCTION: Microcirculatory dysfunction after cardiovascular surgery is associated with significant morbidity and worse clinical outcomes. Abnormal capillary blood flow can occur from multiple causes, including cytokine-mediated vascular endothelial injury, microthrombosis, and an inadequate balance between vasoconstriction and vasodilation. In response to proinflammatory cytokines, endothelial cells produce cellular adhesion molecules (CAMs) which regulate leukocyte adhesion, vascular permeability, and thus can mediate tissue injury. The relationship between changes in microcirculatory flow during circulatory shock and circulating adhesion molecules is unclear. The objective of this study was to compare changes in plasma soluble endothelial cell adhesion molecules (VCAM-1, ICAM-1, and E-Selectin) in patients with functional derangements in microcirculatory blood flow after cardiovascular surgery. METHODS: Adult patients undergoing elective cardiac surgery requiring cardiopulmonary bypass who exhibited postoperative shock were enrolled in the study. Sublingual microcirculation imaging was performed prior to surgery and within 2 h of ICU admission. Blood samples were taken at the time of microcirculation imaging for biomarker analysis. Plasma soluble VCAM-1, ICAM-1, and E-selectin in addition to plasma cytokines (IL-6, IL-8, and IL-10) were measured by commercially available enzyme-linked immunoassay. RESULTS: Of 83 patients with postoperative shock who were evaluated, 40 patients with clinical shock had a postoperative perfused vessel density (PVD) >1 SD above (High PVD group = 28.5 ± 2.3 mm/mm2, n = 20) or below (Low PVD = 15.5 ± 2.0 mm/mm2, n = 20) the mean postoperative PVD and were included in the final analysis. Patient groups were well matched for comorbidities, surgical, and postoperative details. Overall, there was an increase in postoperative plasma VCAM-1 and E-Selectin compared to preoperative levels, but there was no difference between circulating ICAM-1. When grouped by postoperative microcirculation, patients with poor microcirculation were found to have increased circulating VCAM-1 (2413 ± 1144 vs. 844 ± 786 ng/mL; p < 0.0001) and E-Selectin (242 ± 119 vs. 87 ± 86 ng/mL; p < 0.0001) compared to patients with increased microcirculatory blood flow. Microcirculatory flow was not associated with a difference in plasma soluble ICAM-1 (394 ± 190 vs. 441 ± 256; p = 0.52). CONCLUSIONS: Poor postoperative microcirculatory blood flow in patients with circulatory shock after cardiac surgery is associated with increased plasma soluble VCAM-1 and E-Selectin, indicating increased endothelial injury and activation compared to patients with a high postoperative microcirculatory blood flow. Circulating endothelial cell adhesion molecules may be a useful plasma biomarker to identify abnormal microcirculatory blood flow in patients with shock.

Serum lactate in refractory out-of-hospital cardiac arrest: Post-hoc analysis of the Prague OHCA study.

BACKGROUND: The severity of tissue hypoxia is routinely assessed by serum lactate. We aimed to determine whether early lactate levels predict outcomes in refractory out-of-hospital cardiac arrest (OHCA) treated by conventional and extracorporeal cardiopulmonary resuscitation (ECPR). METHODS: This study is a post-hoc analysis of a randomized Prague OHCA study (NCT01511666) assessing serum lactate levels in refractory OHCA treated by ECPR (the ECPR group) or conventional resuscitation with prehospital achieved return of spontaneous circulation (the ROSC group). Lactate concentrations measured on admission and every 4 hours (h) during the first 24 h were used to determine their relationship with the neurological outcome (the best Cerebral Performance Category score within 180 days post-cardiac arrest). RESULTS: In the ECPR group (92 patients, median age 58.5 years, 83% male) 26% attained a favorable neurological outcome. In the ROSC group (82 patients, median age 55 years, 83% male) 59% achieved a favorable neurological outcome. In ECPR patients lactate concentrations could discriminate favorable outcome patients, but not consistently in the ROSC group. On admission, serum lactate >14.0 mmol/L for ECPR (specificity 87.5%, sensitivity 54.4%) and >10.8 mmol/L for the ROSC group (specificity 83%, sensitivity 41.2%) predicted an unfavorable outcome. CONCLUSION: In refractory OHCA serum lactate concentrations measured anytime during the first 24 h after admission to the hospital were found to correlate with the outcome in patients treated by ECPR but not in patients with prehospital ROSC. A single lactate measurement is not enough for a reliable outcome prediction and cannot be used alone to guide treatment.

Doppler identified venous congestion in septic shock: protocol for an international, multi-centre prospective cohort study (Andromeda-VEXUS).

INTRODUCTION: Venous congestion is a pathophysiological state where high venous pressures cause organ oedema and dysfunction. Venous congestion is associated with worse outcomes, particularly acute kidney injury (AKI), for critically ill patients. Venous congestion can be measured by Doppler ultrasound at the bedside through interrogation of the inferior vena cava (IVC), hepatic vein (HV), portal vein (PV) and intrarenal veins (IRV). The objective of this study is to quantify the association between Doppler identified venous congestion and the need for renal replacement therapy (RRT) or death for patients with septic shock. METHODS AND ANALYSIS: This study is a prespecified substudy of the ANDROMEDA-SHOCK 2 (AS-2) randomised control trial (RCT) assessing haemodynamic resuscitation in septic shock and will enrol at least 350 patients across multiple sites. We will include adult patients within 4 hours of fulfilling septic shock definition according to Sepsis-3 consensus conference. Using Doppler ultrasound, physicians will interrogate the IVC, HV, PV and IRV 6-12 hours after randomisation. Study investigators will provide web-based educational sessions to ultrasound operators and adjudicate image acquisition and interpretation. The primary outcome will be RRT or death within 28 days of septic shock. We will assess the hazard of RRT or death as a function of venous congestion using a Cox proportional hazards model. Sub-distribution HRs will describe the hazard of RRT given the competing risk of death. ETHICS AND DISSEMINATION: We obtained ethics approval for the AS-2 RCT, including this observational substudy, from local ethics boards at all participating sites. We will report the findings of this study through open-access publication, presentation at international conferences, a coordinated dissemination strategy by investigators through social media, and an open-access workshop series in multiple languages. TRIAL REGISTRATION NUMBER: NCT05057611.

Direct assessment of microcirculation in shock: a randomized-controlled multicenter study.

PURPOSE: Shock is a life-threatening condition characterized by substantial alterations in the microcirculation. This study tests the hypothesis that considering sublingual microcirculatory perfusion variables in the therapeutic management reduces 30-day mortality in patients admitted to the intensive care unit (ICU) with shock. METHODS: This randomized, prospective clinical multicenter trial-recruited patients with an arterial lactate value above two mmol/L, requiring vasopressors despite adequate fluid resuscitation, regardless of the cause of shock. All patients received sequential sublingual measurements using a sidestream-dark field (SDF) video microscope at admission to the intensive care unit (± 4 h) and 24 (± 4) hours later that was performed blindly to the treatment team. Patients were randomized to usual routine or to integrating sublingual microcirculatory perfusion variables in the therapy plan. The primary endpoint was 30-day mortality, secondary endpoints were length of stay on the ICU and the hospital, and 6-months mortality. RESULTS: Overall, we included 141 patients with cardiogenic (n = 77), post cardiac surgery (n = 27), or septic shock (n = 22). 69 patients were randomized to the intervention and 72 to routine care. No serious adverse events (SAEs) occurred. In the interventional group, significantly more patients received an adjustment (increase or decrease) in vasoactive drugs or fluids (66.7% vs. 41.8%, p = 0.009) within the next hour. Microcirculatory values 24 h after admission and 30-day mortality did not differ [crude: 32 (47.1%) patients versus 25 (34.7%), relative risk (RR) 1.39 (0.91-1.97); Cox-regression: hazard ratio (HR) 1.54 (95% confidence interval (CI) 0.90-2.66, p = 0.118)]. CONCLUSION: Integrating sublingual microcirculatory perfusion variables in the therapy plan resulted in treatment changes that do not improve survival at all.

Immediate Norepinephrine in Endotoxic Shock: Effects on Regional and Microcirculatory Flow.

OBJECTIVES: To investigate the effects of immediate start of norepinephrine versus initial fluid loading followed by norepinephrine on macro hemodynamics, regional splanchnic and intestinal microcirculatory flows in endotoxic shock. DESIGN: Animal experimental study. SETTING: University translational research laboratory. SUBJECTS: Fifteen Landrace pigs. INTERVENTIONS: Shock was induced by escalating dose of lipopolysaccharide. Animals were allocated to immediate start of norepinephrine (i-NE) ( n = 6) versus mandatory 1-hour fluid loading (30 mL/kg) followed by norepinephrine (i-FL) ( n = 6). Once mean arterial pressure greater than or equal to 75 mm Hg was, respectively, achieved, successive mini-fluid boluses of 4 mL/kg of Ringer Lactate were given whenever: a) arterial lactate greater than 2.0 mmol/L or decrease less than 10% per 30 min and b) fluid responsiveness was judged to be positive. Three additional animals were used as controls (Sham) ( n = 3). Time × group interactions were evaluated by repeated-measures analysis of variance. MEASUREMENTS AND MAIN RESULTS: Hypotension was significantly shorter in i-NE group (7.5 min [5.5-22.0 min] vs 49.3 min [29.5-60.0 min]; p < 0.001). Regional mesenteric and microcirculatory flows at jejunal mucosa and serosa were significantly higher in i-NE group at 4 and 6 hours after initiation of therapy ( p = 0.011, p = 0.032, and p = 0.017, respectively). Misdistribution of intestinal microcirculatory blood flow at the onset of shock was significantly reversed in i-NE group ( p < 0.001), which agreed with dynamic changes in mesenteric-lactate levels ( p = 0.01) and venous-to-arterial carbon dioxide differences ( p = 0.001). Animals allocated to i-NE showed significantly higher global end-diastolic volumes ( p = 0.015) and required significantly less resuscitation fluids ( p < 0.001) and lower doses of norepinephrine ( p = 0.001) at the end of the experiment. Pulmonary vascular permeability and extravascular lung water indexes were significantly lower in i-NE group ( p = 0.021 and p = 0.004, respectively). CONCLUSIONS: In endotoxemic shock, immediate start of norepinephrine significantly improved regional splanchnic and intestinal microcirculatory flows when compared with mandatory fixed-dose fluid loading preceding norepinephrine. Immediate norepinephrine strategy was related with less resuscitation fluids and lower vasopressor doses at the end of the experiment.

Improve sleep in critically ill patients: Study protocol for a randomized controlled trial for a multi-component intervention of environment control in the ICU.

INTRODUCTION: In critically ill patients, sleep and circadian rhythms are greatly altered. These disturbances have been associated with adverse consequences, including increased mortality. Factors associated with the ICU environment, such as exposure to inadequate light and noise levels during the day and night or inflexible schedules of daily care activities, have been described as playing an essential role in sleep disturbances. The main objective of this study is to evaluate the impact of the use of a multifaceted environmental control intervention in the ICU on the quantity and quality of sleep, delirium, and post-intensive care neuropsychological impairment in critically ill patients. METHODS: This is a prospective, parallel-group, randomized trial in 56 critically ill patients once they are starting to recover from their acute illness. Patients will be randomized to receive a multifaceted intervention of environmental control in the ICU (dynamic light therapy, auditory masking, and rationalization of ICU nocturnal patient care activities) or standard care. The protocol will be applied from enrollment until ICU discharge. Baseline parameters, light and noise levels, polysomnography and actigraphy, daily oscillation of plasma concentrations of Melatonin and Cortisol, and questionnaires for the qualitative evaluation of sleep, will be assessed during the study. In addition, all patients will undergo standardized follow-up before hospital discharge and at 6 months to evaluate neuropsychological impairment. DISCUSSION: This study is the first randomized clinical trial in critically ill patients to evaluate the effect of a multicomponent, non-pharmacological environmental control intervention on sleep improvement in ICU patients. The results will provide data about the potential synergistic effects of a combined multi-component environmental intervention in ICU on outcomes in the ICU and long term, and the mechanism of action. TRIAL REGISTRATION: ClinicalTrials.gov, NCT. Registered on January 10, 2023. Last updated on 24 Jan 2023.

Exploring the relationship between capillary refill time, skin blood flow and microcirculatory reactivity during early resuscitation of patients with septic shock: a pilot study.

Capillary refill time (CRT), a costless and widely available tool, has emerged as a promising target to guide septic shock resuscitation. However, it has yet to gain universal acceptance due to its potential inter-observer variability. Standardization of CRT assessment may minimize this problem, but few studies have compared this approach with techniques that directly assess skin blood flow (SBF). Our objective was to determine if an abnormal CRT is associated with impaired SBF and microvascular reactivity in early septic shock patients. Twelve septic shock patients were subjected to multimodal perfusion and hemodynamic monitoring for 24 h. Three time-points (0, 1, and 24 h) were registered for each patient. SBF was measured by laser doppler. We performed a baseline SBF measurement and two microvascular reactivity tests: one with a thermal challenge at 44 °C and other with a vascular occlusion test. Ten healthy volunteers were evaluated to obtain reference values. The patients (median age 70 years) exhibited a 28-day mortality of 50%. Baseline CRT was 3.3 [2.7-7.3] seconds. In pooled data analysis, abnormal CRT presented a significantly lower SBF when compared to normal CRT [44 (13.3-80.3) vs 193.2 (99.4-285) APU, p = 0.0001]. CRT was strongly associated with SBF (R2 0.76, p < 0.0001). An abnormal CRT also was associated with impaired thermal challenge and vascular occlusion tests. Abnormal CRT values observed during early septic shock resuscitation are associated with impaired skin blood flow, and abnormal skin microvascular reactivity. Future studies should confirm these results.