Balanced crystalloids versus saline in critically ill adults with low plasma bicarbonate: A secondary analysis of a clinical trial
Journal of critical care. 2021
PURPOSE We aimed to determine if balanced crystalloids compared with saline improve outcomes in critically ill adults admitted with low plasma bicarbonate. MATERIALS AND METHODS We performed a secondary analysis of the Isotonic Solutions and Major Adverse Renal Events Trial (SMART). We included patients who presented to the Emergency Department with a first measured plasma bicarbonate less than 20 mmol/L. Among these patients, we compared the effect of balanced crystalloid versus saline on the primary outcome of major adverse kidney events within 30 days (MAKE30), defined as a composite of death, new renal-replacement therapy, or persistent renal dysfunction (final inpatient creatinine ≥200% baseline). Secondary outcomes included 30 day in-hospital mortality, receipt of new RRT, persistent renal dysfunction, incident AKI, and vasopressor-free days. RESULTS Among the 2029 patients with an initial plasma bicarbonate concentration < 20 mmol/L, there was no difference in the incidence of MAKE30 between those assigned to balanced crystalloid versus saline (21.8% vs 21.3%; P = 0.93). Secondary outcomes were similar between the balanced crystalloid and saline groups. CONCLUSIONS Among critically ill adults presenting to the Emergency Department, initial plasma bicarbonate concentration does not appear to be a useful marker to guide the selection of balanced crystalloid versus saline.
Randomized Controlled Trial of Ultrasound-guided Fluid Resuscitation of Sepsis-Induced Hypoperfusion and Septic Shock
The western journal of emergency medicine. 2021;22(2):369-378
INTRODUCTION The ultrasound measurement of inferior vena cava (IVC) diameter change during respiratory phase to guide fluid resuscitation in shock patients is widely performed, but the benefit on reducing the mortality of sepsis patients is questionable. The study objective was to evaluate the 30-day mortality rate of patients with sepsis-induced tissue hypoperfusion (SITH) and septic shock (SS) treated with ultrasound-guided fluid management (UGFM) using ultrasonographic change of the IVC diameter during respiration compared with those treated with the usual-care strategy. METHODS This was a randomized controlled trial conducted in an urban, university-affiliated tertiary-care hospital. Adult patients with SITH/SS were randomized to receive treatment with UGFM using respiratory change of the IVC (UGFM strategy) or with the usual-care strategy during the first six hours after emergency department (ED) arrival. We compared the 30-day mortality rate and other clinical outcomes between the two groups. RESULTS A total of 202 patients were enrolled, 101 in each group (UGFM vs usual-care strategy) for intention-to-treat analysis. There was no significant difference in 30-day overall mortality between the two groups (18.8% and 19.8% in the usual-care and UGFM strategy, respectively; p > 0.05 by log rank test). Neither was there a difference in six-hour lactate clearance, a change in the sequential organ failure assessment score, or length of hospital stay. However, the cumulative fluid amount given in 24 hours was significantly lower in the UGFM arm. CONCLUSION In our ED setting, the use of respiratory change of IVC diameter determined by point-of-care ultrasound to guide initial fluid resuscitation in SITH/SS ED patients did not improve the 30-day survival probability or other clinical parameters compared to the usual-care strategy. However, the IVC ultrasound-guided resuscitation was associated with less amount of fluid used.
The effects of a limited infusion rate of fluid in the early resuscitation of sepsis on glycocalyx shedding measured by plasma syndecan-1: a randomized controlled trial
Journal of intensive care. 2021;9(1):1
BACKGROUND Aggressive fluid administration is recommended in the resuscitation of septic patients. However, the delivery of a rapid fluid bolus might cause harm by inducing degradation of the endothelial glycocalyx. This research aimed to examine the effects of the limited infusion rate of fluid on glycocalyx shedding as measured by syndecan-1 in patients with sepsis-induced hypoperfusion. METHODS A prospective, randomized, controlled, open-label trial was conducted between November 2018 and February 2020 in an urban academic emergency department. Patients with sepsis-induced hypoperfusion, defined as hypotension or hyperlactatemia, were randomized to receive either the standard rate (30 ml/kg/h) or limited rate (10 ml/kg/h) of fluid for the first 30 ml/kg fluid resuscitation. Subsequently, the fluid rate was adjusted according to the physician's discretion but not more than that of the designated fluid rate for the total of 6 h. The primary outcome was differences in change of syndecan-1 levels at 6 h compared to baseline between standard and limited rate groups. Secondary outcomes included adverse events, organ failure, and 90-day mortality. RESULTS We included 96 patients in the intention-to-treat analysis, with 48 assigned to the standard-rate strategy and 48 to the limited-rate strategy. The median fluid volume in 6 h in the limited-rate group was 39 ml/kg (interquartile range [IQR] 35-52 ml/kg) vs. 53 ml/kg (IQR 46-64 ml/kg) in the standard-rate group (p < 0.001). Patients in the limited-rate group were less likely to received vasopressors (17% vs 42%; p = 0.007) and mechanical ventilation (20% vs 41%; p = 0.049) during the first 6 h. There were no significantly different changes in syndecan-1 levels at 6 h between the two groups (geometric mean ratio [GMR] in the limited-rate group, 0.82; 95% confidence interval [CI], 0.66-1.02; p = 0.07). There were no significant differences in adverse events, organ failure outcomes, or mortality between the two groups. CONCLUSIONS In sepsis resuscitation, the limited rate of fluid resuscitation compared to the standard rate did not significantly reduce changes in syndecan-1 at 6 h. TRIAL REGISTRATION Thai Clinical Trials Registry number: TCTR20181010001. Registered 8 October 2018, http://www.clinicaltrials.in.th/index.php?tp=regtrials&menu=trialsearch&smenu=fulltext&task=search&task2=view1&id=4064.
Balanced Salt Solution Versus Normal Saline in Resuscitation of Pediatric Sepsis: A Randomized, Controlled Trial
Indian journal of pediatrics. 2021;:1-4
Current evidences in resuscitation of adult sepsis have pointed to the importance of types of crystalloid fluid-related complications on resuscitation outcomes, but evidences are lacking in pediatric populations. In this study, the authors aimed to compare outcomes of pediatric sepsis resuscitation with different types of crystalloid. They randomly assigned pediatric sepsis patients requiring fluid bolus into three groups to receive either normal saline solution (NSS), Ringer lactate solution (RLS), or Sterofundin as fluid bolus therapy. Forty-two patients were included in the study. Median age was 29 mo and, weight 13 kg. After fluid bolus, the complications were not different among groups. However, in the RLS group, the patients who received large dose of the fluid showed significant reduction in urinary neutrophil gelatinase-associated lipocalin (uNGAL) level. It is concluded that fluid bolus therapy with different types of crystalloid solution did not result in different outcomes but large dose of RLS was associated with greater reduction of uNGAL level, compared to other fluids.Trial Registration: Thai Clinical Trial Registry (TCTR) identification number TCTR20170605001 (retrospectively registered on 1st June 2017). https://www.clinicaltrials.in.th/index.php?tp=regtrials&menu=trialsearch&smenu=fulltext&task20=search&task2=view1&id=2576.
[Randomized controlled multicenter study of albumin replacement therapy in septic shock (ARISS)]
Der Anaesthesist. 2021
Early Lactate-Guided Resuscitation of Elderly Septic Patients
Journal of intensive care medicine. 2021;:8850666211023347
BACKGROUND Early lactate-guided resuscitation was endorsed in the guidelines of the Surviving Sepsis Campaign as a key strategy to decrease the mortality of patients admitted to the ICU department with septic shock. However, its effectiveness in elderly Asian patients is uncertain. METHOD We conducted a single-center trial to test the effectiveness of the early lactate-guided resuscitation of older Asian patients at the Second Hospital of Hebei Medical University. Eligible septic shock patients who consented to participation in the study were randomly assigned to receive early lactate-guided treatment or regular treatment as controls. RESULT A total of 82 patients met the hyperlactatemia criteria and participated in the trial. Forty-two patients received early lactate-guided treatment (lactate group) and 40 received regular treatment (control group). The lactate group received more fluids at initial 6 hours (3.3 ± 1.4 vs 2.4 ± 1.7 L, P = 0.01), but similar proportions of patients in both groups required the use of vasopressors and vasodilators. Patients in the lactate group showed significantly reduced ICU needs compared to the control group, which were weaned from mechanical ventilation more quickly (median 7, IQR 4 to 14 vs median 9, IQR 4.3 to 17.8, P = 0.02) and transferred out of the ICU earlier (median 4.5, IQR 2.8 to 7.3 vs median 6, IQR 3.2 to 8, P = 0.01). However, the hospital mortality (35.7% vs 42.5%, P = 0.35) and ICU mortality (31.0% vs 37.5%, P = 0.38) for both groups were not reduced. CONCLUSION For critically ill patients (elderly Asian patients) admitted to the ICU department with hyperlactatemia, early lactate-guided treatment reduced ICU needs but did not reduce mortality.
Comparison of 5% human albumin and normal saline for fluid resuscitation in sepsis induced hypotension among patients with cirrhosis (FRISC study): a randomized controlled trial
Hepatology international. 2021
AIMS: Sepsis and septic shock are common causes of hospitalization and mortality in patients with cirrhosis. There is no data on the choice of fluid and resuscitation protocols in sepsis-induced hypotension in cirrhosis. METHODS In this open-label trial conducted at a single center, we enrolled 308 cirrhotics with sepsis-induced hypotension and randomized them to receive either 5% albumin or normal saline. The primary endpoint was a reversal of hypotension [mean arterial pressure, MAP, ≥ 65 mmHg] at 3 h. Secondary endpoints included serial effects on heart rate, arterial lactate and urine output. RESULTS 154 patients each received 5% albumin (males, 79.8%, mean MAP 52.9 ± 7.0 mm Hg) or 0.9% saline (85.1%, 53.4 ± 6.3 mm Hg) with comparable baseline parameters and liver disease severity. Reversal of hypotension was higher in patients receiving 5% albumin than saline at the end of one hour [25.3% and 11.7%, p = 0.03, Odds ratio (95% CI)-1.9 (1.08-3.42)] and at the end of three hours [11.7% and 3.2%, p = 0.008, 3.9 (1.42-10.9)]. Sustained reduction in heart rate and hyperlactatemia (p < 0.001) was better in the albumin group. At one week, the proportion of patients surviving was higher in the albumin group than those receiving saline (43.5% vs 38.3%, p = 0.03). Female gender and SOFA ≥ 11 were predictors of non-response to fluid. CONCLUSIONS 5% human albumin is safe and beneficial in reversing sepsis-induced hypotension compared to normal saline in patients with cirrhosis improving clinically assessable parameters of systemic hemodynamics, tissue perfusion and in-hospital short-term survival of cirrhosis patients with sepsis.
Albumin replacement therapy in immunocompromised patients with sepsis - Secondary analysis of the ALBIOS trial
Journal of critical care. 2021;63:83-91
BACKGROUND The best fluid replacement strategy and the role of albumin in immunocompromised patients with sepsis is unclear. METHODS We performed a secondary analysis of immunocompromised patients enrolled in the ALBIOS trial which randomized patients with severe sepsis or septic shock to receive either 20% albumin (target 30 g per liter or more) and crystalloid or crystalloid alone during ICU stay. RESULTS Of 1818 patients originally enrolled, 304 (16.4%) were immunocompromised. One-hundred-thirty-nine (45.7%) patients were randomized in the albumin while 165 (54.2%) in the crystalloid group. At 90 days, 69 (49.6%) in the albumin group and 89 (53.9%) in the crystalloids group died (hazard ratio - HR - 0.94; 95% CI 0.69-1.29). No differences were observed with regards to 28-day mortality, SOFA score (and sub-scores), length of stay in the ICU and in the hospital, proportion of patients who had developed acute kidney injury or received renal replacement therapy, duration of mechanical ventilation. Albumin was not independently associated with a higher or lower 90-day mortality (HR 0.979, 95% CI 0.709-1.352) as compared to crystalloid. CONCLUSION Albumin replacement during the ICU stay, as compared with crystalloids alone, did not affect clinical outcomes in a cohort of immunocompromised patients with sepsis.
Systematic assessment of fluid responsiveness during early septic shock resuscitation: secondary analysis of the ANDROMEDA-SHOCK trial
Critical care (London, England). 2020;24(1):23
BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS 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. TRIAL REGISTRATION ClinicalTrials.gov identifier, NCT03078712. Registered retrospectively on March 13, 2017.
0.9% Saline v/s Ringer's Lactate for fl uid resuscitation in adult sepsis patients in emergency medical services: An open label Randomized Controlled trial
The Journal of the Association of Physicians of India. 2020;68(1):87