Prevalence of antibiotic use for childhood diarrhoea in Uganda after an ORS scale-up intervention: a repeated cross-sectional study.

BACKGROUND: Diarrhoea kills 500,000 children every year despite availability of cheap and effective treatment. In addition, a large number are inappropriately treated with antibiotics, which do not benefit the patient but can contribute to the development of antibiotic resistance. We investigated whether the prevalence of antibiotic use among children under the age of five with diarrhoea in Uganda changed following a national intervention to increase the use of oral rehydration salts (ORS), and whether any socioeconomic characteristics were associated with antibiotic use. METHODS: A cross-sectional survey was conducted among caregivers of children under the age of five and among private health care providers and drug sellers in Uganda in 2014. This was compared to a similar survey among private health care providers, and the national demographic and health survey in Uganda in 2016. Logistic regression was used to find associations between antibiotic use and socioeconomic characteristics, and chi-square test and independent sample t-test were used to find significant differences between groups. RESULTS: The prevalence of antibiotic use among children under the age of five with diarrhoea in Uganda decreased from 30.5% in 2014 to 20.0% (p < 0.001) in 2016. No associations between socioeconomic characteristics and the use of antibiotics were significant in both 2014 and 2016. CONCLUSIONS: The use of antibiotics in children with diarrhoeal disease decreased significantly in Uganda between 2014 and 2016. However, the extent of the contribution of the ORS scale-up programme to this decrease cannot be determined from this study.

Assessment of fluid responsiveness using pulse pressure variation, stroke volume variation, plethysmographic variability index, central venous pressure, and inferior vena cava variation in patients undergoing mechanical ventilation: a systematic review and meta-analysis.

IMPORTANCE: Maneuvers assessing fluid responsiveness before an intravascular volume expansion may limit useless fluid administration, which in turn may improve outcomes. OBJECTIVE: To describe maneuvers for assessing fluid responsiveness in mechanically ventilated patients. REGISTRATION: The protocol was registered at PROSPERO: CRD42019146781. INFORMATION SOURCES AND SEARCH: PubMed, EMBASE, CINAHL, SCOPUS, and Web of Science were search from inception to 08/08/2023. STUDY SELECTION AND DATA COLLECTION: Prospective and intervention studies were selected. STATISTICAL ANALYSIS: Data for each maneuver were reported individually and data from the five most employed maneuvers were aggregated. A traditional and a Bayesian meta-analysis approach were performed. RESULTS: A total of 69 studies, encompassing 3185 fluid challenges and 2711 patients were analyzed. The prevalence of fluid responsiveness was 49.9%. Pulse pressure variation (PPV) was studied in 40 studies, mean threshold with 95% confidence intervals (95% CI) = 11.5 (10.5-12.4)%, and area under the receiver operating characteristics curve (AUC) with 95% CI was 0.87 (0.84-0.90). Stroke volume variation (SVV) was studied in 24 studies, mean threshold with 95% CI = 12.1 (10.9-13.3)%, and AUC with 95% CI was 0.87 (0.84-0.91). The plethysmographic variability index (PVI) was studied in 17 studies, mean threshold = 13.8 (12.3-15.3)%, and AUC was 0.88 (0.82-0.94). Central venous pressure (CVP) was studied in 12 studies, mean threshold with 95% CI = 9.0 (7.7-10.1) mmHg, and AUC with 95% CI was 0.77 (0.69-0.87). Inferior vena cava variation (∆IVC) was studied in 8 studies, mean threshold = 15.4 (13.3-17.6)%, and AUC with 95% CI was 0.83 (0.78-0.89). CONCLUSIONS: Fluid responsiveness can be reliably assessed in adult patients under mechanical ventilation. Among the five maneuvers compared in predicting fluid responsiveness, PPV, SVV, and PVI were superior to CVP and ∆IVC. However, there is no data supporting any of the above mentioned as being the best maneuver. Additionally, other well-established tests, such as the passive leg raising test, end-expiratory occlusion test, and tidal volume challenge, are also reliable.

Twenty percent human albumin solution fluid bolus administration therapy in patients after cardiac surgery-II: a multicentre randomised controlled trial.

PURPOSE: After cardiac surgery, fluid bolus therapy (FBT) with 20% human albumin may facilitate less fluid and vasopressor administration than FBT with crystalloids. We aimed to determine whether, after cardiac surgery, FBT with 20% albumin reduces the duration of vasopressor therapy compared with crystalloid FBT. METHODS: We conducted a multicentre, parallel-group, open-label, randomised clinical trial in six intensive care units (ICUs) involving cardiac surgery patients deemed to require FBT. We randomised 240 patients to receive up to 400 mL of 20% albumin/day as FBT, followed by 4% albumin for any subsequent FBT on that day, or to crystalloid FBT for at least the first 1000 mL, with use of crystalloid or 4% albumin FBT thereafter. The primary outcome was the cumulative duration of vasopressor therapy. Secondary outcomes included fluid balance. RESULTS: Of 480 randomised patients, 466 provided consent and contributed to the primary outcome (mean age 65 years; median EuroSCORE II 1.4). The cumulative median duration of vasopressor therapy was 7 (interquartile range [IQR] 0-19.6) hours with 20% albumin and 10.8 (IQR 0-22.8) hours with crystalloids (difference - 3.8 h, 95% confidence interval [CI] - 8 to 0.4; P = 0.08). Day one fluid balance was less with 20% albumin FBT (mean difference - 701 mL, 95% CI - 872 to - 530). CONCLUSIONS: In patients after cardiac surgery, when compared to a crystalloid-based FBT, 20% albumin FBT was associated with a reduced positive fluid balance but did not significantly reduce the duration of vasopressor therapy.

Fluid administration and fluid accumulation in intensive care units-Protocol for an international inception cohort study (FLUID-ICU).

INTRODUCTION: Fluid accumulation is associated with adverse outcomes in critically ill patients admitted to the intensive care unit (ICU). Fluid administration in the ICU may be a clinically relevant source of fluid accumulation in ICU patients. However, the extent is unknown, and no standard definition exists. We aim to provide epidemiological data on fluid accumulation, risk factors, use of fluid removal strategies, patient outcomes and describe current fluid administration practices in the ICU. METHODS: We will conduct an international 14-day inception cohort study including a minimum of 1000 acutely admitted adult ICU patients. Data will be collected from medical records and laboratory reports at baseline and daily from ICU admission to discharge with a maximum of 28 days. Follow-up will be performed on day 90 after inclusion. The primary outcome is the number of patients with fluid accumulation. Secondary outcomes include the number of days with fluid accumulation, use of active fluid removal, days alive without life support at day 28, days alive and out of hospital day 90, and all-cause mortality at day 90. Furthermore, we will assess risk factors for fluid accumulation and its association with 90-day mortality and report on the types of fluid administration. CONCLUSION: This international inception cohort study will provide contemporary epidemiological data on fluid administration and fluid accumulation in adult ICU patients.

Prospective observational study of peripheral intravenous cannula utilisation and frequency of intravenous fluid delivery in the emergency department-Convenience or necessity?

BACKGROUND: Peripheral Intravenous Cannulas (PIVCs) are frequently utilised in the Emergency Department (ED) for delivery of medication and phlebotomy. They are associated with complications and have an associated cost to departmental resources. A growing body of international research suggests many of the PIVCs inserted in the ED are unnecessary. METHODS: The objective of this study was to determine the rates of PIVC insertion and use. This was a prospective observational study conducted in one UK ED and one Italian ED. Adult ED patients with non-immediate triage categories were included over a period of three weeks in the UK ED in August 2016 and two weeks in the Italian ED in March and August 2017. Episodes of PIVC insertion and data on PIVC utilisation in adults were recorded. PIVC use was classified as necessary, unnecessary or unused. The proportion of unnecessary and unused PIVCs was calculated. PIVCs were defined as unnecessary if they were either used for phlebotomy only, or solely for IV fluids in patients that could have potentially been hydrated orally (determined against a priori defined criteria). PIVC classified as unused were not used for any purpose. RESULTS: A total of 1,618 patients were included amongst which 977 PIVCs were inserted. Of the 977 PIVCs, 413 (42%) were necessary, 536 (55%) were unnecessary, and 28 (3%) were unused. Of the unnecessary PIVCs, 473 (48%) were used solely for phlebotomy and 63 (6%) were used for IV fluids in patients that could drink. CONCLUSIONS: More than half of PIVCs placed in the ED were unnecessary in this study. This suggests that clinical decision making about the benefits and risks of PIVC insertion is not being performed on an individual basis.

Prevalence of oral rehydration solution use and its determinants in the treatment of diarrhea among under-five children in sub-Saharan Africa.

BACKGROUND: Diarrhea is the second leading cause of under-five deaths claiming half a million children every year. Most of these deaths occurred in sub-Saharan Africa and South Asia. Oral rehydration solution (ORS) has been described as the most effective treatment of diarrhea. However, only 36% of children with diarrhea received ORS in sub-Saharan Africa. This study examined the factors associated with ORS use for children with diarrhea in the sub-region. METHODS: Demographic and Health Surveys (DHS) data sets of 31 countries in sub-Saharan Africa were used in this study. The data involved 30,102 under-five children with diarrhea. The multivariable analysis involved binary logistic regression. RESULTS: Prevalence of ORS use was 38% in sub-Saharan Africa with countries such as Namibia (71.8%), Zambia (66.4%) and Malawi (63.8%) having the highest rates. Use of ORS was most common among children whose mothers had secondary or higher education (45%), were exposed to media (41%) and attended antenatal care (41%). ORS use was significantly associated with secondary or higher education (OR = 1.63; 95%CI: [1.47-1.81]; p<0.001), exposure to media (OR = 1.17; 95%CI: [1.07-1.27]; p<0.001), antenatal care attendance (OR = 2.33; 95%CI: [1.08-1.27]; p<0.001), child's age (OR = 1.46; 95%CI: [1.35-1.59]; p<0.001), child's size at birth (OR = 1.08; 95%CI: [1.00-1.17]; p<0.05), household size (OR = 1.28; 95%CI:[1.06-1.54]; p<0.05) and source of drinking water (OR = 1.18; 95%CI: [1.09-1.29]; p<0.001). CONCLUSION: This study revealed a 38% prevalence of ORS use during diarrhea episodes in sub-Saharan Africa. This is low as it is less than the 44% recorded for developing countries as a whole. While this study emphasises the need for a further study on effects of severity of diarrhea on ORS use and factors determining differences in ORS use among countries, it also calls for interventions that will increase use of ORS is sub-Saharan Africa. Such interventions should include increase in literacy rate among girls and women, increase in the proportion of women with access to media, involvement of health workers in programmes that would promote antenatal care utilization among women at community level and provision of social amenities like pipe-borne water.

Factors associated with the co-utilization of oral rehydration solution and zinc for treating diarrhea among under-five children in 35 sub-saharan Africa countries: a generalized linear mixed effect modeling with robust error variance.

INTRODUCTION: Even though childhood diarrhea is treated with a simple treatment solution, it continues to be one of the leading causes of under-five child mortality and malnutrition globally. In resource-limited settings such as Sub-Saharan Africa (SSA), the combination of oral rehydration salts (ORS) and zinc is regarded as an effective treatment for diarrhea; however, its utilization is very low. The purpose of this study was to determine the proportion and associated factors of co-utilization of ORS and zinc among under-five children with diarrhea in SSA. METHODS: The proportion and associated factors of co-utilization of ORS and zinc among under-five children with diarrhea in SSA were determined using secondary data analysis of recent Demographic and Health Surveys (DHS) of 35 SSA countries. The study included a total of 44,341 under-five children with diarrhea in weighted samples. A generalized linear mixed-effects model with robust error variance was used. For the variables included in the final model, adjusted prevalence ratios (aPR) with 95% confidence intervals (CI) were estimated. A model with the lowest deviance value were considered as the best-fitted model. RESULT: The pooled proportion of co-utilization of ORS and zinc for the treatment of diarrhea among under five children in SSA countries was 43.58% with a 95% CI (43.15%, 44.01%). Sex of the child, maternal age, residence, maternal educational and employment status, wealth index, media exposure, perceived distance to health facility and insurance coverage were statistically significant determinants of ORS and Zinc co-utilization for treating diarrhea among under five children in SSA. CONCLUSION: Only less than half of under-five children with diarrhea in SSA were treated with a combination of ORS and zinc. Thus, strengthening information dissemination through mass media, and community-level health education programs are important to scale up the utilization of the recommended combination treatment. Furthermore, increasing health insurance coverage, and establishing strategies to address the community with difficulty in accessing health facilities is also crucial in improving the use of the treatment.

Subcutaneous administration of drugs and hydration in acute palliative care units: Physician attitudes and beliefs in the United States and Canada.

OBJECTIVES: The objective of this study was to compare the attitudes and beliefs of PCU physicians leaders in the United States versus Canada regarding the subcutaneous method in the administration of medications and hydration in order to gain a better understanding as to why variations in practice exist. METHODS: This survey trial took place from November 2022 to May 2023. The MD Anderson Cancer Center institutional review board in Houston, Texas, approved this study. The participants were the physician leaders of the acute palliative care units (PCUs) in the United States and Canada. The survey comprised questions formulated by the study investigators regarding the perceived comfort, efficiency, and preference of using the subcutaneous versus the intravenous method. The consent form and survey links were emailed to the participants. RESULTS: Sixteen PCUs were identified in the United States and 15 PCUs in Canada. Nine US and 8 Canadian physicians completed the survey. Physicians in Canada were more likely to use the subcutaneous route for administering opioids, antiemetics, neuroleptics, and hydration. They preferred subcutaneous over intravenous or intramuscular routes (p = 0.017). Canadian physicians felt their nursing staff was more comfortable with subcutaneous administration (p = 0.022) and that it was easier to administer (p = 0.02). US physicians felt the intravenous route was more efficient (p = 0.013). SIGNIFICANCE OF RESULTS: The study results suggest that exposure to the subcutaneous route influences a physician's perception. Further research is needed to explore ways to incorporate its use to a greater degree in the US healthcare system.

Fluid Balance and Ventilator-Associated Events Among Patients Admitted to ICUs in China: A Nested Case-Control Study.

OBJECTIVES: Fluid therapy is an important component of intensive care management, however, optimal fluid management is unknown. The relationship between fluid balance and ventilator-associated events has not been well established. This study investigated the dose-response relationship between fluid balance and ventilator-associated events. DESIGN: Nested case-control study. SETTING: The study was based on a well-established, research-oriented registry of healthcare-associated infections at ICUs of West China Hospital system (Chengdu, China). PATIENTS: A total of 1,528 ventilator-associated event cases with 3,038 matched controls, who consistently underwent mechanical ventilation for at least 4 days from April 1, 2015, to December 31, 2018, were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We calculated cumulative fluid balance within 4 days prior to ventilator-associated event occurrence. A weighted Cox proportional hazards model with restricted cubic splines was used to evaluate the dose-response relationship. A nonlinear relationship between fluid balance and all three tiers of ventilator-associated events, patients with fluid balance between -1 and 0 L had the lowest risk (p < 0.05 for nonlinear test). The risk of ventilator-associated event was significantly higher in patients with positive fluid balance (4 d cumulative fluid balance: 1 L: 1.19; 3 L: 1.92; 5 L: 2.58; 7 L: 3.24), but not in those with negative fluid balance (-5 L: 1.34; -3 L: 1.14; -1 L: 0.98). CONCLUSIONS: There was nonlinear relationship between fluid balance and all three tiers of ventilator-associated event, with an fluid balance between -1 and 0 L corresponding to the lowest risk. Positive but not negative fluid balance increased the risk of ventilator-associated events, with higher positive fluid balance more likely to lead to ventilator-associated events.

Standardized hospital management of pediatric diabetic ketoacidosis reduces frequency of low blood glucose episodes.

OBJECTIVE: In patients treated for DKA, decrease the rate of visits experiencing one or more BG < 80 mg/dl by 10% within 24 months. RESEARCH DESIGN AND METHODS: Plan-do-study-act cycles tested interventions linked to key drivers including: standardized DKA guidelines incorporating a two-bag fluid system, efficient ordering process, and care team education. Inclusion criterion: treatment for DKA with a bicarbonate value (HCO3 ) <15 mEq/L. PRIMARY OUTCOME: the percent of patient visits experiencing a BG < 80 mg/dl while undergoing treatment for DKA. Process measures included: order panel and order set utilization rates. Balancing measures included: emergency department and hospital lengths of stay, time to acidosis resolution (time to HCO3 ≥ 17 mEq/L), and admission rates. Outcomes were analyzed using statistical process control charts. RESULTS: From January 2017 through May 2021, our institution treated 288 different patients during 557 visits for suspected DKA. Following our interventions, the overall percent of patient visits for DKA with a BG < 80 mg/dl improved from 32% to 5%. The team did see small improvements in emergency department and hospital lengths of stay; otherwise, there was no significant change in our balancing measures. CONCLUSIONS: Use of quality improvement methodology and standardized DKA management resulted in a significant reduction of BG < 80 mg/dl in patients treated for DKA.

Association of fluid balance trajectories with clinical outcomes in patients with septic shock: a prospective multicenter cohort study.

BACKGROUND: Septic shock has a high incidence and mortality rate in Intensive Care Units (ICUs). Earlier intravenous fluid resuscitation can significantly improve outcomes in septic patients but easily leads to fluid overload (FO), which is associated with poor clinical outcomes. A single point value of fluid cannot provide enough fluid information. The aim of this study was to investigate the impact of fluid balance (FB) latent trajectories on clinical outcomes in septic patients. METHODS: Patients were diagnosed with septic shock during the first 48 h, and sequential fluid data for the first 3 days of ICU admission were included. A group-based trajectory model (GBTM) which is designed to identify groups of individuals following similar developmental trajectories was used to identify latent subgroups of individuals following a similar progression of FB. The primary outcomes were hospital mortality, organ dysfunction, major adverse kidney events (MAKE) and severe respiratory adverse events (SRAE). We used multivariable Cox or logistic regression analysis to assess the association between FB trajectories and clinical outcomes. RESULTS: Nine hundred eighty-six patients met the inclusion criteria and were assigned to GBTM analysis, and three latent FB trajectories were detected. 64 (6.5%), 841 (85.3%), and 81 (8.2%) patients were identified to have decreased, low, and high FB, respectively. Compared with low FB, high FB was associated with increased hospital mortality [hazard ratio (HR) 1.63, 95% confidence interval (CI) 1.22-2.17], organ dysfunction [odds ratio (OR) 2.18, 95% CI 1.22-3.42], MAKE (OR 1.80, 95% CI 1.04-2.63) and SRAE (OR 2.33, 95% CI 1.46-3.71), and decreasing FB was significantly associated with decreased MAKE (OR 0.46, 95% CI 0.29-0.79) after adjustment for potential covariates. CONCLUSION: Latent subgroups of septic patients followed a similar FB progression. These latent fluid trajectories were associated with clinical outcomes. The decreasing FB trajectory was associated with a decreased risk of hospital mortality and MAKE.

Critical care ultrasound in geriatric trauma resuscitation leads to decreased fluid administration and ventilator days.

BACKGROUND: Geriatric trauma populations respond differently than younger trauma populations. Critical care ultrasound (CCUS) can guide resuscitation, and it has been shown to decrease intravenous fluid (IVF), lower time until operation, and lower mortality in trauma. Critical care ultrasound-guided resuscitation has not yet been studied in geriatric trauma. We hypothesized that incorporation of CCUS would decrease amount of IVF administered, decrease time to initiation of vasopressors, and decrease end organ dysfunction. METHODS: A PRE-CCUS geriatric trauma group between January 2015 and October 2016 was resuscitated per standard practice. A POST-CCUS group between January 2017 and December 2018 was resuscitated based on CCUS performed by trained intensivist upon admission to the intensive care unit and 6 hours after initial ultrasound. The PRE-CCUS and POST-CCUS groups underwent propensity score matching, yielding 60 enrollees in each arm. Retrospective review was conducted for demographics, clinical outcomes, and primary endpoints, including amount of IVF in the first 48 hours, duration to initiation of vasopressor use, and end organ dysfunction. Wilcoxon two-sample, χ2 tests, and κ statistics were performed to check associations between groups. RESULTS: There was no statistical difference between PRE-CCUS and POST-CCUS demographics and Injury Severity Scores. Intravenous fluid within 48 hours decreased from median [interquartile range] of 4941 mL [4019 mL] in the PRE-CCUS to 2633 mL [3671 mL] in the POST-CCUS (p = 0.0003). There was no significant difference between the two groups in time to initiation of vasopressors, vasopressor duration, lactate clearance, intensive care unit length of stay, or hospital length of stay. There was a significant decrease in ventilator days, with 26.7% PRE-CCUS with ventilation longer than 2 days, and only 6.7% POST-CCUS requiring ventilation longer than 2 days (p = 0.0033). CONCLUSION: Critical care ultrasound can be a useful addition to geriatric resuscitation. The POST-CCUS received less IV fluid and had decreased ventilator days. While mortality, lactate clearance, complications, and hospital stay were not statistically different, there was a perception that CCUS was a useful adjunct for assessing volume status and cardiac function. LEVEL OF EVIDENCE: Therapeutic, level II.

Individualized resuscitation strategy for septic shock formalized by finite mixture modeling and dynamic treatment regimen.

BACKGROUND: Septic shock comprises a heterogeneous population, and individualized resuscitation strategy is of vital importance. The study aimed to identify subclasses of septic shock with non-supervised learning algorithms, so as to tailor resuscitation strategy for each class. METHODS: Patients with septic shock in 25 tertiary care teaching hospitals in China from January 2016 to December 2017 were enrolled in the study. Clinical and laboratory variables were collected on days 0, 1, 2, 3 and 7 after ICU admission. Subclasses of septic shock were identified by both finite mixture modeling and K-means clustering. Individualized fluid volume and norepinephrine dose were estimated using dynamic treatment regime (DTR) model to optimize the final mortality outcome. DTR models were validated in the eICU Collaborative Research Database (eICU-CRD) dataset. RESULTS: A total of 1437 patients with a mortality rate of 29% were included for analysis. The finite mixture modeling and K-means clustering robustly identified five classes of septic shock. Class 1 (baseline class) accounted for the majority of patients over all days; class 2 (critical class) had the highest severity of illness; class 3 (renal dysfunction) was characterized by renal dysfunction; class 4 (respiratory failure class) was characterized by respiratory failure; and class 5 (mild class) was characterized by the lowest mortality rate (21%). The optimal fluid infusion followed the resuscitation/de-resuscitation phases with initial large volume infusion and late restricted volume infusion. While class 1 transitioned to de-resuscitation phase on day 3, class 3 transitioned on day 1. Classes 1 and 3 might benefit from early use of norepinephrine, and class 2 can benefit from delayed use of norepinephrine while waiting for adequate fluid infusion. CONCLUSIONS: Septic shock comprises a heterogeneous population that can be robustly classified into five phenotypes. These classes can be easily identified with routine clinical variables and can help to tailor resuscitation strategy in the context of precise medicine.

A Multicentric, Randomized, Controlled Phase III Study of Centhaquine (Lyfaquin®) as a Resuscitative Agent in Hypovolemic Shock Patients.

INTRODUCTION: Centhaquine (Lyfaquin®) showed significant safety and efficacy in preclinical and clinical phase I and II studies. METHODS: A prospective, multicentric, randomized phase III study was conducted in patients with hypovolemic shock, systolic blood pressure (SBP) ≤ 90 mmHg, and blood lactate levels ≥ 2 mmol/L. Patients were randomized in a 2:1 ratio to the centhaquine group (n = 71) or the control (saline) group (n = 34). Every patient received standard of care (SOC) and was followed for 28 days. The study drug (normal saline or centhaquine 0.01 mg/kg) was administered in 100 mL of normal saline infusion over 1 h. The primary objectives were to determine changes (mean through 48 h) in SBP, diastolic blood pressure (DBP), blood lactate levels, and base deficit. The secondary objectives included the amount of fluids, blood products, and vasopressors administered in the first 48 h, duration of hospital stay, time in intensive care units, time on ventilator support, change in acute respiratory distress syndrome (ARDS), multiple organ dysfunction syndrome (MODS), and the proportion of patients with 28-day all-cause mortality. RESULTS: The demographics of patients and baseline vitals in both groups were comparable. The cause of hypovolemic shock was trauma in 29.4 and 47.1% of control group and centhaquine group patients, respectively, and gastroenteritis in 44.1 and 29.4%, respectively. Shock index (SI) and quick sequential organ failure assessment at baseline were similar in the two groups. An equal amount of fluids and blood products were administered in both groups during the first 48 h of resuscitation. A lesser amount of vasopressors was needed in the first 48 h of resuscitation in the centhaquine group. An increase in SBP from baseline was consistently higher up to 48 h (12.9% increase in area under the curve from 0 to 48 h [AUC0-48]) in the centhaquine group than in the control group. A significant increase in pulse pressure (48.1% increase in AUC0-48) in the centhaquine group compared with the control group suggests improved stroke volume due to centhaquine. The SI was significantly lower in the centhaquine group from 1 h (p = 0.032) to 4 h (p = 0.049) of resuscitation. Resuscitation with centhaquine resulted in a significantly greater number of patients with improved blood lactate (control 46.9%; centhaquine 69.3%; p = 0.03) and the base deficit (control 43.7%; centhaquine 69.8%; p = 0.01) than in the control group. ARDS and MODS improved with centhaquine, and an 8.8% absolute reduction in 28-day all-cause mortality was observed in the centhaquine group. CONCLUSION: Centhaquine is an efficacious resuscitative agent for treating hypovolemic shock. The efficacy of centhaquine in distributive shock is being explored. TRIAL REGISTRATION: Clinical Trials Registry, India; ctri.icmr.org.in, CTRI/2019/01/017196; clinicaltrials.gov, NCT04045327.

Comparison of fluid resuscitation weight-based dosing strategies in obese patients with severe sepsis.

OBJECTIVE: This study aims to compare the composite outcome of progression to septic shock between 30 mL/kg/ideal body weight (IBW) versus 30 mL/kg/non-IBW fluid resuscitation dosing strategies in obese patients with severe sepsis. METHODS: We retrospectively evaluated obese patients admitted to an academic tertiary care center for the management of severe sepsis. Patients were included if they had a fluid bolus order placed using the sepsis order set between Oct 2018 and Sept 2019. The primary objective was the composite of progression to septic shock, defined as either persistent hypotension within 3 h after the conclusion of the 30 mL/kg fluid bolus administration or the initiation of vasopressor(s) within 6 h of the bolus administration. RESULTS: Of 72 included patients, 49 (68%) were resuscitated using an IBW-based and 23 (32%) using a non-IBW-based dosing strategy. There were similar rates of progression to septic shock in the IBW and non-IBW groups (18% vs. 26%; p = 0.54). Median ICU and hospital LOS in the IBW group versus non-IBW group were (0 [IQR 0] vs. 0 [IQR 0 to 4] days; p = 0.13) and (6 [IQR 3 to 10] vs. 8 [IQR 5 to 12] days; p = 0.07), respectively. In-hospital mortality rates were similar between the groups. CONCLUSIONS: Our study results suggest that in obese septic patients, fluid administration using an IBW-dosing strategy did not affect the progression to septic shock.

Clinical factors associated with rapid treatment of sepsis.

PURPOSE: To understand what clinical presenting features of sepsis patients are historically associated with rapid treatment involving antibiotics and fluids, as appropriate. DESIGN: This was a retrospective, observational cohort study using a machine-learning model with an embedded feature selection mechanism (gradient boosting machine). METHODS: For adult patients (age ≥ 18 years) who were admitted through Emergency Department (ED) meeting clinical criteria of severe sepsis from 11/2007 to 05/2018 at an urban tertiary academic medical center, we developed gradient boosting models (GBMs) using a total of 760 original and derived variables, including demographic variables, laboratory values, vital signs, infection diagnosis present on admission, and historical comorbidities. We identified the most impactful factors having strong association with rapid treatment, and further applied the Shapley Additive exPlanation (SHAP) values to examine the marginal effects for each factor. RESULTS: For the subgroups with or without fluid bolus treatment component, the models achieved high accuracy of area-under-receiver-operating-curve of 0.91 [95% CI, 0.86-0.95] and 0.84 [95% CI, 0.81-0.86], and sensitivity of 0.81[95% CI, 0.72-0.87] and 0.91 [95% CI, 0.81-0.97], respectively. We identified the 20 most impactful factors associated with rapid treatment for each subgroup. In the non-hypotensive subgroup, initial physiological values were the most impactful to the model, while in the fluid bolus subgroup, value minima and maxima tended to be the most impactful. CONCLUSION: These machine learning methods identified factors associated with rapid treatment of severe sepsis patients from a large volume of high-dimensional clinical data. The results provide insight into differences in the rapid provision of treatment among patients with sepsis.

Quality Gaps in Management of Acute Pancreatitis: A Tertiary Care Center Experience.

OBJECTIVES: Acute pancreatitis (AP) is a leading cause of inpatient care among gastrointestinal conditions. Our study compares the management of AP and adherence to guidelines among teaching medicine, nonteaching medicine, and surgical services within the same center. METHODS: We performed a retrospective chart review of AP patients admitted to our center between January 2016 and January 2017 and analyzed the clinical and epidemiological data. RESULTS: Of 115 patients, 65% were admitted to medicine (IM), and 35% were admitted to surgery. Mean age was 53.9 (standard deviation [SD], 15) years, and 52% were males; 38.6% (n = 29) of IM patients were prescribed lactated Ringer's solution for fluid resuscitation (mean rate of 153 [SD, 44.98] mL/h on teaching and 113 [SD, 43.56] mL/h on the nonteaching service). Antibiotics were prescribed to 22.6% (n = 17) of IM patients. On the surgical service, 77.5% of patients were prescribed lactated Ringer's solution for fluid resuscitation (mean rate of 108.25 [SD, 1.19] mL/h); 52.5% of patients received antibiotics. CONCLUSIONS: Adherence to guidelines for management of AP is inadequate, and nonuniformity exists across different services within the same institution. There is a need for quality improvement initiatives.

Association between perioperative fluid administration and postoperative outcomes: a 20-year systematic review and a meta-analysis of randomized goal-directed trials in major visceral/noncardiac surgery.

BACKGROUND: Appropriate perioperative fluid management is of pivotal importance to reduce postoperative complications, which impact on early and long-term patient outcome. The so-called perioperative goal-directed therapy (GDT) approach aims at customizing perioperative fluid management on the individual patients' hemodynamic response. Whether or not the overall amount of perioperative volume infused in the context of GDT could influence postoperative surgical outcomes is unclear. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing the efficacy of GDT approach between study population and control group in reducing postoperative complications and perioperative mortality, using MEDLINE, EMBASE and the Cochrane Controlled Clinical trials register. The enrolled studies were grouped considering the amount infused intraoperatively and during the first 24 h after the admission in the critical care unit (perioperative fluid). RESULTS: The metanalysis included 21 RCTs enrolling 2729 patients with a median amount of perioperative fluid infusion of 4500 ml. In the studies reporting an overall amount below or above this threshold, the differences in postoperative complications were not statically significant between controls and GDT subgroup [43.4% vs. 34.2%, p value = 0.23 and 54.8% vs. 39.8%; p value = 0.09, respectively]. Overall, GDT reduced the overall rate of postoperative complications, as compared to controls [pooled risk difference (95% CI) = - 0.10 (- 0.14, - 0.07); Chi2 = 30.97; p value < 0.0001], but not to a reduction of perioperative mortality [pooled risk difference (95%CI) = - 0.016 (- 0.0334; 0.0014); p value = 0.07]. Considering the rate of organ-related postoperative events, GDT did not reduce neither renal (p value = 0.52) nor cardiovascular (p value = 0.86) or pulmonary (p value = 0.14) or neurological (p value = 0.44) or infective (p value = 0.12) complications. CONCLUSIONS: Irrespectively to the amount of perioperative fluid administered, GDT strategy reduces postoperative complications, but not perioperative mortality. TRIAL REGISTRATION: CRD42020168866; Registration: February 2020 https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=168866.

Acetate Ringer's solution versus 0.9% saline for septic patients: study protocol for a multi-center parallel controlled trial.

BACKGROUND: Previous study drew different conclusions on significant differences between saline and balanced crystalloid solution infused in critical illness but both showed a statistical difference in the sepsis subgroup. Thus, we will specifically focus on septic patients in this study to compare the effects of saline and balanced solution. We hypothesize that effects of saline on renal outcomes are related to the underline acute kidney injury (AKI) severity and total volumes of infusion. METHODS/DESIGN: The investigators designed a pragmatic, multi-center parallel controlled trial recruiting 312 patients who are diagnosed with sepsis/septic shock in the intensive care unit (ICU) and will be assigned with either acetate Ringer's solution or saline in the corresponding month. Patients with an end-stage renal disease (ESRD) or who need renal replacement therapy (RRT) prior to or at the time of enrolment are excluded. Enrolled patients will be regarded as with mild, moderate, or severe sepsis on the basis of the severity of their illness and will be divided into subgroups according to their initial renal function and various intravenous infusion volumes when being analyzed. The primary outcome is major adverse kidney events within 28 days (MAKE28), including the composite of in-hospital death, receipt of new renal replacement therapy, or persistent renal dysfunction. Secondary outcomes include 28-day mortality, internal environment disturbance, incidence and duration of vasoactive drug treatment, duration of mechanical ventilation, duration of RRT, and ICU and hospital length of stay. RESULTS AND CONCLUSIONS: To our knowledge, this study will be the first to focus on septic patients and provide credible and evident data on the comparison of outcome between acetate Ringer's solution and saline for intravenous infusion in adult septic patients on the basis of baseline renal function and infusion volumes taken into consideration. TRIAL REGISTRATION: ClinicalTrials.gov NCT03685214 . Registered on August 15, 2018.

Emergency nurses' experiences of the implementation of early goal directed fluid resuscitation therapy in the management of sepsis: a qualitative study.

BACKGROUND: Severe sepsis can lead to organ failure and death if immediate treatment, such as intravenous fluids and antibiotics, are not commenced within the first hour. Time - critical initiation of intravenous fluids which in other words is early goal directed fluid resuscitation has not always been given its clinical priority. This qualitative study aimed at exploring the experiences of emergency nurses initiating early goal directed fluid resuscitation in patients with sepsis. METHODS: Using an exploratory approach, face - to - face semi - structured interviews were conducted with ten registered nurses working in emergency departments across New South Wales, Australia. Thematic analysis was used for data analysis. FINDINGS: Participants described various factors that inhibited the timely initiation of early goal directed fluid resuscitation, some clinical practice challenges, and strategies to improve nursing practice. Most participants, particularly those practicing as Clinical Initiatives Nurses suggested the incorporation of nurse initiated early goal directed fluid resuscitation for patients with sepsis as part of their scope of practice. CONCLUSION: Our findings identified several barriers that inhibit effective nurse - initiated early goal directed fluid resuscitation. It is anticipated that these findings will provide validation for the re-evaluation of the existing protocols and practice guidelines to increase the scope of practice of emergency nurses initiating early goal directed fluid resuscitation.