Acute circulatory dysfunction in patients with sepsis can evolve rapidly into a progressive stage associated with high mortality. Early recognition and adequate resuscitation could improve outcome. ...However, since the spectrum of clinical presentation is quite variable, signs of hypoperfusion are frequently unrecognized in patients just admitted to the emergency department (ED). Hyperlactatemia is considered a key parameter to disclose tissue hypoxia but it is not universally available and getting timely results can be challenging in low resource settings. In addition, non-hypoxic sources can be involved in hyperlactatemia, and a misinterpretation could lead to over-resuscitation in an unknown number of cases. Capillary refill time (CRT) is a marker of peripheral perfusion that worsens during circulatory failure. An abnormal CRT in septic shock patients after ICU-based resuscitation has been associated with poor outcome. The aim of this study was to determine the prevalence of abnormal CRT in patients with sepsis-related hyperlactatemia in the early phase after ED admission, and its relationship with outcome.
We performed a prospective observational study. Septic patients with hyperlactemia at ED admission subjected to an initial fluid resuscitation (FR) were included. CRT and other parameters were assessed before and after FR. CRT-normal or CRT-abnormal subgroups were defined according to the status of CRT following initial FR, and major outcomes were registered.
Ninety-five hyperlactatemic septic patients were included. Thirty-one percent had abnormal CRT at ED arrival. After FR, 87 patients exhibited normal CRT, and 8 an abnormal one. Patients with abnormal CRT had an increased risk of adverse outcomes (88% vs. 20% p<0.001; RR 4.4 2.7-7.4), and hospital mortality (63% vs. 9% p<0.001; RR 6.7 2.9-16) as compared to those with normal CRT after FR. Specifically, CRT-normal patients required less frequently mechanical ventilation, renal replacement therapy, and ICU admission, and exhibited a lower hospital mortality.
Hyperlactatemic sepsis patients with abnormal CRT after initial fluid resuscitation exhibit higher mortality and worse clinical outcomes than patients with normal CRT.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Based on these data and our previous unpublished local experience for a decade, we decided to use NS due to its more favorable distribution, as it is widely known that administration of 5% dextrose ...impacts mainly the intracellular compartment, with negligible effect on intravascular when compared to NS, even in cases when capillary integrity is present 6. Randomized controlled trial Ibarra-Estrada M, Kattan E, Aguilera-González P, Sandoval-Plascencia L, Rico-Jauregui U, Gómez-Partida CA, et al. Early adjunctive methylene blue in patients with septic shock: a randomized controlled trial.
Fluid boluses are administered to septic shock patients with the purpose of increasing cardiac output as a means to restore tissue perfusion. Unfortunately, fluid therapy has a narrow therapeutic ...index, and therefore, several approaches to increase safety have been proposed. Fluid responsiveness (FR) assessment might predict which patients will effectively increase cardiac output after a fluid bolus (FR+), thus preventing potentially harmful fluid administration in non-fluid responsive (FR-) patients. However, there are scarce data on the impact of assessing FR on major outcomes. The recent ANDROMEDA-SHOCK trial included systematic per-protocol assessment of FR. We performed a post hoc analysis of the study dataset with the aim of exploring the relationship between FR status at baseline, attainment of specific targets, and clinically relevant outcomes.
ANDROMEDA-SHOCK compared the effect of peripheral perfusion- vs. lactate-targeted resuscitation on 28-day mortality. FR was assessed before each fluid bolus and periodically thereafter. FR+ and FR- subgroups, independent of the original randomization, were compared for fluid administration, achievement of resuscitation targets, vasoactive agents use, and major outcomes such as organ dysfunction and support, length of stay, and 28-day mortality.
FR could be determined in 348 patients at baseline. Two hundred and forty-two patients (70%) were categorized as fluid responders. Both groups achieved comparable successful resuscitation targets, although non-fluid responders received less resuscitation fluids (0 0-500 vs. 1500 1000-2500 mL; p 0.0001), exhibited less positive fluid balances, but received more vasopressor testing. No difference in clinically relevant outcomes between FR+ and FR- patients was found, including 24-h SOFA score (9 5-12 vs. 8 5-11, p = 0.4), need for MV (78% vs. 72%, p = 0.16), need for RRT (18% vs. 21%, p = 0.7), ICU-LOS (6 3-11 vs. 6 3-16 days, p = 0.2), and 28-day mortality (40% vs. 36%, p = 0.5). Only thirteen patients remained fluid responsive along the intervention period.
Systematic assessment allowed determination of fluid responsiveness status in more than 80% of patients with early septic shock. Fluid boluses could be stopped in non-fluid responsive patients without any negative impact on clinical relevant outcomes. Our results suggest that fluid resuscitation might be safely guided by FR assessment in septic shock patients.
ClinicalTrials.gov identifier, NCT03078712. Registered retrospectively on March 13, 2017.
Methylene blue (MB) has been tested as a rescue therapy for patients with refractory septic shock. However, there is a lack of evidence on MB as an adjuvant therapy, its' optimal timing, dosing and ...safety profile. We aimed to assess whether early adjunctive MB can reduce time to vasopressor discontinuation in patients with septic shock.
In this single-center randomized controlled trial, we assigned patients with septic shock according to Sepsis-3 criteria to MB or placebo. Primary outcome was time to vasopressor discontinuation at 28 days. Secondary outcomes included vasopressor-free days at 28 days, days on mechanical ventilator, length of stay in ICU and hospital, and mortality at 28 days.
Among 91 randomized patients, forty-five were assigned to MB and 46 to placebo. The MB group had a shorter time to vasopressor discontinuation (69 h IQR 59-83 vs 94 h IQR 74-141; p < 0.001), one more day of vasopressor-free days at day 28 (p = 0.008), a shorter ICU length of stay by 1.5 days (p = 0.039) and shorter hospital length of stay by 2.7 days (p = 0.027) compared to patients in the control group. Days on mechanical ventilator and mortality were similar. There were no serious adverse effects related to MB administration.
In patients with septic shock, MB initiated within 24 h reduced time to vasopressor discontinuation and increased vasopressor-free days at 28 days. It also reduced length of stay in ICU and hospital without adverse effects. Our study supports further research regarding MB in larger randomized clinical trials. Trial registration ClinicalTrials.gov registration number NCT04446871 , June 25, 2020, retrospectively registered.
Background
Capillary refill time (CRT) may improve more rapidly than lactate in response to increments in systemic flow. Therefore, it can be assessed more frequently during septic shock (SS) ...resuscitation. Hyperlactatemia, in contrast, exhibits a slower recovery in SS survivors, probably explained by the delayed resolution of non-hypoperfusion-related sources. Thus, targeting lactate normalization may be associated with impaired outcomes. The ANDROMEDA-SHOCK trial compared CRT- versus lactate-targeted resuscitation in early SS. CRT-targeted resuscitation associated with lower mortality and organ dysfunction; mechanisms were not investigated. CRT was assessed every 30 min and lactate every 2 h during the 8-h intervention period, allowing a first comparison between groups at 2 h (T2). Our primary aim was to determine if SS patients evolving with normal CRT at T2 after randomization (T0) exhibited a higher mortality and organ dysfunction when allocated to the LT arm than when randomized to the CRT arm. Our secondary aim was to determine if those patients with normal CRT at T2 had received more therapeutic interventions when randomized to the LT arm. To address these issues, we performed a post hoc analysis of the ANDROMEDA-SHOCK dataset.
Results
Patients randomized to the lactate arm at T0, evolving with normal CRT at T2 exhibited significantly higher mortality than patients with normal CRT at T2 initially allocated to CRT (40 vs 23%,
p
= 0.009). These results replicated at T8 and T24. LT arm received significantly more resuscitative interventions (fluid boluses: 1000500–2000 vs. 5000–1500,
p
= 0.004; norepinephrine test in previously hypertensive patients: 43 (35) vs. 19 (19),
p
= 0.001; and inodilators: 16 (13) vs. 3 (3),
p
= 0.003). A multivariate logistic regression of patients with normal CRT at T2, including APACHE-II, baseline lactate, cumulative fluids administered since emergency admission, source of infection, and randomization group) confirmed that allocation to LT group was a statistically significant determinant of 28-day mortality (OR 3.3; 95%CI1.5–7.1);
p
= 0.003).
Conclusions
Septic shock patients with normal CRT at baseline received more therapeutic interventions and presented more organ dysfunction when allocated to the lactate group. This could associate with worse outcomes.
Toxic epidermal necrolysis (TEN) is a rare, acute mucocutaneous life-threatening disease. Although research has focused on the pathophysiological and therapeutic aspects of the disease, there is a ...paucity of data in the literature regarding pain management and sedation in the intensive care unit (ICU). Most therapies have been extrapolated from other situations and/or the general ICU population. These patients present unique challenges during the progression of the disease and could end up requiring invasive mechanical ventilation due to inadequate pain management, which is potentially avoidable through a comprehensive treatment approach. In this review, we will present clinical and pathophysiological aspects of TEN, analyze pain pathways and relevant pharmacology, and propose therapeutic alternatives based on a rational and multimodal approach.
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.
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.
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.
NCT05057611.
Background
Persistent hyperlactatemia has been considered as a signal of tissue hypoperfusion in septic shock patients, but multiple non-hypoperfusion-related pathogenic mechanisms could be involved. ...Therefore, pursuing lactate normalization may lead to the risk of fluid overload. Peripheral perfusion, assessed by the capillary refill time (CRT), could be an effective alternative resuscitation target as recently demonstrated by the ANDROMEDA-SHOCK trial. We designed the present randomized controlled trial to address the impact of a CRT-targeted (CRT-T) vs. a lactate-targeted (LAC-T) fluid resuscitation strategy on fluid balances within 24 h of septic shock diagnosis. In addition, we compared the effects of both strategies on organ dysfunction, regional and microcirculatory flow, and tissue hypoxia surrogates.
Results
Forty-two fluid-responsive septic shock patients were randomized into CRT-T or LAC-T groups. Fluids were administered until target achievement during the 6 h intervention period, or until safety criteria were met. CRT-T was aimed at CRT normalization (≤ 3 s), whereas in LAC-T the goal was lactate normalization (≤ 2 mmol/L) or a 20% decrease every 2 h. Multimodal perfusion monitoring included sublingual microcirculatory assessment; plasma-disappearance rate of indocyanine green; muscle oxygen saturation; central venous-arterial pCO
2
gradient/ arterial-venous O
2
content difference ratio; and lactate/pyruvate ratio. There was no difference between CRT-T vs. LAC-T in 6 h-fluid boluses (875 375–2625 vs. 1500 1000–2000,
p
= 0.3), or balances (982249–2833 vs. 15,800 740–6587,
p
= 0.2). CRT-T was associated with a higher achievement of the predefined perfusion target (62 vs. 24,
p
= 0.03). No significant differences in perfusion-related variables or hypoxia surrogates were observed.
Conclusions
CRT-targeted fluid resuscitation was not superior to a lactate-targeted one on fluid administration or balances. However, it was associated with comparable effects on regional and microcirculatory flow parameters and hypoxia surrogates, and a faster achievement of the predefined resuscitation target. Our data suggest that stopping fluids in patients with CRT ≤ 3 s appears as safe in terms of tissue perfusion.
Clinical Trials: ClinicalTrials.gov Identifier: NCT03762005 (Retrospectively registered on December 3rd 2018)
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