Association Between Furosemide Exposure and Clinical Outcomes in a Retrospective Cohort of Critically Ill Children

Furosemide is commonly prescribed in critically ill patients to increase the urine output and prevent fluid overload (FO) and acute kidney injury (AKI), but not supported by conclusive evidence. There remain conflicting findings on whether furosemide associates with AKI and adverse outcomes. Information on the impact of furosemide on adverse outcomes in a general population of pediatric intensive care unit (PICU) is limited. The aim of the cohort study was to investigate the associations of furosemide with AKI and clinical outcomes in critically ill children.Study Design: We retrospectively reviewed a cohort of 456 critically ill children consecutively admitted to PICU from January to December 2016. The exposure of interest was the use of furosemide in the first week after admission. FO was defined as ≥5% of daily fluid accumulation, and mean FO was considered significant when mean daily fluid accumulation during the first week was ≥5%. The primary outcomes were AKI in the first week after admission and mortality during PICU stay. AKI diagnosis was based on Kidney Disease: Improving Global Outcomes criteria with both serum creatinine and urine output.Results: Furosemide exposure occurred in 43.4% of all patients (n = 456) and 49.3% of those who developed FO (n = 150) in the first week after admission. Patients who were exposed to furosemide had significantly less degree of mean daily fluid accumulation than those who were not (1.10 [−0.33 to 2.61%] vs. 2.00 [0.54–3.70%], P < 0.001). There was no difference in the occurrence of AKI between patients who did and did not receive furosemide (22 of 198 [11.1%] vs. 36 of 258 [14.0%], P = 0.397). The mortality rate was 15.4% (70 of 456), and death occurred more frequently among patients who received furosemide than among those who did not (21.7 vs. 10.5%, P = 0.002). Furosemide exposure was associated with increased odds for mortality in a multivariate logistic regression model adjusted for body weight, gender, illness severity assessed by PRISM III score, the presence of mean FO, and AKI stage [adjusted odds ratio (AOR) 1.95; 95%CI, 1.08–3.52; P = 0.026].Conclusion: Exposure to furosemide might be associated with increased risk for mortality, but not AKI, in critically ill children.

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Atrial fibrillation and clinical outcomes 1 to 3 years after myocardial infarction

Open Heart ◽

10.1136/openhrt-2021-001726 ◽

2021 ◽

Vol 8 (2) ◽

pp. e001726

Author(s):

Anthony P Carnicelli ◽

Ruth Owen ◽

Stuart J Pocock ◽

David B Brieger ◽

Satoshi Yasuda ◽

...

Keyword(s):

Quality Of Life ◽

Myocardial Infarction ◽

Atrial Fibrillation ◽

Clinical Outcomes ◽

Oral Anticoagulants ◽

Adverse Outcomes ◽

Increased Risk ◽

History Of ◽

The Impact

ObjectiveAtrial fibrillation (AF) and myocardial infarction (MI) are commonly comorbid and associated with adverse outcomes. Little is known about the impact of AF on quality of life and outcomes post-MI. We compared characteristics, quality of life and clinical outcomes in stable patients post-MI with/without AF.Methods/resultsThe prospective, international, observational TIGRIS (long Term rIsk, clinical manaGement and healthcare Resource utilization of stable coronary artery dISease) registry included 8406 patients aged ≥50 years with ≥1 atherothrombotic risk factor who were 1–3 years post-MI. Patient characteristics were summarised by history of AF. Quality of life was assessed at baseline using EQ-5D. Clinical outcomes over 2 years of follow-up were compared. History of AF was present in 702/8277 (8.5%) registry patients and incident AF was diagnosed in 244/7575 (3.2%) over 2 years. Those with AF were older and had more comorbidities than those without AF. After multivariable adjustment, patients with AF had lower self-reported quality-of-life scores (EQ-5D UK-weighted index, visual analogue scale, usual activities and pain/discomfort) than those without AF. CHA2DS2-VASc score ≥2 was present in 686/702 (97.7%) patients with AF, although only 348/702 (49.6%) were on oral anticoagulants at enrolment. Patients with AF had higher rates of all-cause hospitalisation (adjusted rate ratio 1.25 [1.06–1.46], p=0.008) over 2 years than those without AF, but similar rates of mortality.ConclusionsIn stable patients post-MI, those with AF were commonly undertreated with oral anticoagulants, had poorer quality of life and had increased risk of clinical outcomes than those without AF.Trial registration numberClinicalTrials: NCT01866904.

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Intravenous Fluid Prescription Practices in Critically Ill Children: A Shift in Focus from Natremia to Chloremia?

Journal of Pediatric Intensive Care ◽

10.1055/s-0039-1692413 ◽

2019 ◽

Vol 08 (04) ◽

pp. 218-225

Author(s):

Adrian F. Bulfon ◽

Hakem L. Alomani ◽

Natalie Anton ◽

Brooke T. Comrie ◽

Bram Rochwerg ◽

...

Keyword(s):

Critically Ill ◽

Tertiary Care ◽

Significant Proportion ◽

Daily Intake ◽

Adverse Outcomes ◽

Critically Ill Children ◽

Salt Solutions ◽

Eligibility Criteria ◽

Maintenance Fluid ◽

Increased Risk

AbstractOur objective is to evaluate intravenous (IV) fluid prescription practice patterns in critically ill children in the first 72 hours of pediatric intensive care unit (PICU) admission and to evaluate the incidence and predictors of hyperchloremic metabolic acidemia (HCMA) and the association between HCMA and adverse outcomes. This retrospective cohort study was conducted in two tertiary-care Canadian PICUs. Children aged 0 to 18 years admitted to the PICU between January 2015 and January 2016 who received at least 50% of their calculated maintenance fluid requirements parenterally during the first 24 hours of admission were included. Children with known preexisting conditions associated with HCMA, such as renal tubular acidosis and gastrointestinal bicarbonate losses, were excluded. Of the 771 children screened, 543 met eligibility criteria and were included. The commonest prescribed maintenance fluid was 0.9% NaCl (72.9%) followed by lactated Ringer's solution (19.6%) and hypotonic solutions (4.6%). Balanced salt solutions (i.e., lactated Ringer's and Plasma-Lyte) were as commonly administered as unbalanced solutions (0.9% NaCl) for volume expansion (49.6 vs. 48.5%, respectively). Medications contributed to a significant proportion of total daily intake, in excess of bolus fluids. The incidence of hyperchloremia and HCMA was 94.9% (95% confidence interval [CI]: 93.2–96.9; 470/495) and 38.9% (95% CI: 34.6–43.2; 196/504), respectively. Predictors of HCMA were increasing combined bolus and maintenance 0.9% NaCl intake (odds ratio: 1.13; 95% CI: 1.04–1.23) and increasing severity of illness. HCMA was not associated with an increased risk of acute kidney injury, feeding intolerance, or PICU-acquired weakness. Isotonic fluids, specifically 0.9% NaCl, were the most commonly administered maintenance IV fluid in critically ill children. Sources of chloride load are not isolated to resuscitation fluids as previously suggested. Maintenance fluids and fluids administered with medications and IV flushes (fluid creep) are under-recognized significant sources of fluid and electrolyte intake in critically ill children. HCMA is common, and further prospective research is required to determine whether HCMA is indeed harmful in children. However, all significant sources of fluid should be accounted for in the design of future trials comparing balanced and unbalanced salt solutions.

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Effect of Red Blood Cell Transfusions on Clinical Outcomes in Critically Ill Children

Blood ◽

10.1182/blood.v128.22.3851.3851 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3851-3851

Author(s):

Irina B. Pateva ◽

Steven L Shein ◽

MaryAnn O'Riordan ◽

Sanjay P Ahuja

Keyword(s):

Mechanical Ventilation ◽

Length Of Stay ◽

Blood Cell ◽

Clinical Outcomes ◽

Critically Ill ◽

Age Groups ◽

Critically Ill Children ◽

Age Group ◽

Vasoactive Agents ◽

The Impact

Abstract Introduction: The association of packed Red Blood Cell (pRBC) transfusions with worse outcomes in critically ill adults is well documented. The impact of pRBC transfusions on clinical outcomes in critically ill children, however, has not been well studied. Associations of pRBCs with outcomes such as mortality and length of stay need to be studied in large clinical databases. This will lead to improvement of our knowledge and generation of guidelines for transfusions in children hospitalized in the Pediatric Intensive Care Units (PICU). Methods: With IRB approval, the Pediatric Health Information System (PHIS) database was queried for children ≤ 18 years admitted to the PICU, receiving pRBC transfusions between January 2011 and December 2015. The PHIS is a database that captures de-identified patient information from 45 pediatric hospitals in the US. The patients of this study were stratified by age groups: less than 1 month of age; 1 month to < 3years; 3 to <10 years; 10 to < 15 years and 15 to 18 years. Patients with underlying hematological or oncological diagnoses and who had undergone HSCT were excluded from the study. Information regarding major comorbidities such as mechanical ventilation, sepsis, use of vasoactive agents, acute kidney injury (AKI) and post-operative state were extracted. Patients who received pRBCs and who did not receive pRBCs were included in the analyses. The primary outcomes were Length of Stay (LOS) and mortality. Multiple linear and logistic regression analyses were performed to define the association between pRBC transfusions and outcomes and to control for sepsis, mechanical ventilation, vasoactive medications, post-operative state and AKI. Data are shown as median (IQR). Results: Of the 393,384 patients who met the inclusion criteria, 43,569 (11%) had transfusions, with 97.2% of the patients receiving only 1 transfusion. The median (IQR) overall length of stay was 5.0 days (2, 10) and the overall mortality was 3.1%. The median (IQR) LOS for those who received pRBCs was 13 days (6, 29) compared to 4.0 days (2, 8) for those who did not. Mortality for those who received pRBCs was 10.1% compared to 2.2% for those who did not. The highest rate of pRBC transfusion was noted in the patients less than 1 month old (22%). The highest unadjusted mortality for patients who received pRBCs was also in the same age group- 7%. The associations between transfusion of pRBCs and outcomes are summarized in Table 1. Of the 393,384 patients, 19,686 (5.0 %) had sepsis; 143,085 (36.4%) were on mechanical ventilation; 141,123 (35.9%) were on vasoactive agents and 14,243 (3.6%) had AKI. After adjusting for sepsis, mechanical ventilation, use of vasoactive agents, post-op state and AKI, pRBC transfusions were associated with significantly increased LOS for all age groups. The highest increase in LOS was noted for the infants younger than 1 month of age - by 11.6 days (p<0.001). The mortality was also increased in patients who received PRBCs, when adjusted for other comorbidites, the highest risk was for patients in the age group of 15 to 18 years old: OR 2.50 (95% CI 2.14- 2.93). Conclusions: In this large, multicenter database study, we identified an association of increased mortality and LOS in critically ill children who received pRBC transfusions. More studies are needed to further investigate the impact of blood transfusions on clinical outcomes in the pediatric population. Disclosures No relevant conflicts of interest to declare.

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Association of Fluid Accumulation with Clinical Outcomes in Critically Ill Children with Severe Sepsis

PLoS ONE ◽

10.1371/journal.pone.0160093 ◽

2016 ◽

Vol 11 (7) ◽

pp. e0160093 ◽

Cited By ~ 22

Author(s):

Jiao Chen ◽

Xiaozhong Li ◽

Zhenjiang Bai ◽

Fang Fang ◽

Jun Hua ◽

...

Keyword(s):

Severe Sepsis ◽

Clinical Outcomes ◽

Critically Ill ◽

Critically Ill Children ◽

Fluid Accumulation

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Epidemiology of Bleeding in Critically Ill Children

Frontiers in Pediatrics ◽

10.3389/fped.2021.699991 ◽

2021 ◽

Vol 9 ◽

Author(s):

Jake Sequeira ◽

Marianne E. Nellis ◽

Oliver Karam

Keyword(s):

Critical Care ◽

Critically Ill ◽

Critical Care Unit ◽

Critically Ill Children ◽

Pediatric Critical Care ◽

Risk Of Mortality ◽

Increased Risk ◽

Duration Of Surgery ◽

The Impact ◽

Bleeding Severity

Objective: Bleeding can be a severe complication of critical illness, but its true epidemiologic impact on children has seldom been studied. Our objective is to describe the epidemiology of bleeding in critically ill children, using a validated clinical tool, as well as the hemostatic interventions and clinical outcomes associated with bleeding.Design: Prospective observational cohort study.Setting: Tertiary pediatric critical care unitPatients: All consecutive patients (1 month to 18 years of age) admitted to a tertiary pediatric critical care unitMeasurements and Main Results: Bleeding events were categorized as minimal, moderate, severe, or fatal, according to the Bleeding Assessment Scale in Critically Ill Children. We collected demographics and severity at admission, as evaluated by the Pediatric Index of Mortality. We used regression models to compare the severity of bleeding with outcomes adjusting for age, surgery, and severity. Over 12 months, 902 critically ill patients were enrolled. The median age was 64 months (IQR 17; 159), the median admission predicted risk of mortality was 0.5% (IQR 0.2; 1.4), and 24% were post-surgical. Eighteen percent of patients experienced at least one bleeding event. The highest severity of bleeding was minimal for 7.9% of patients, moderate for 5.8%, severe for 3.8%, and fatal for 0.1%. Adjusting for age, severity at admission, medical diagnosis, type of surgery, and duration of surgery, bleeding severity was independently associated with fewer ventilator-free days (p < 0.001) and fewer PICU-free days (p < 0.001). Adjusting for the same variables, bleeding severity was independently associated with an increased risk of mortality (adjusted odds ratio for each bleeding category 2.4, 95% CI 1.5; 3.7, p < 0.001).Conclusion: Our data indicate bleeding occurs in nearly one-fifth of all critically ill children, and that higher severity of bleeding was independently associated with worse clinical outcome. Further multicenter studies are required to better understand the impact of bleeding in critically ill children.

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Renal Dysfunction Criteria in Critically Ill Children: The PODIUM Consensus Conference

PEDIATRICS ◽

10.1542/peds.2021-052888j ◽

2022 ◽

Vol 149 (Supplement_1) ◽

pp. S66-S73

Author(s):

Julie C. Fitzgerald ◽

Rajit K. Basu ◽

Dana Y. Fuhrman ◽

Stephen M. Gorga ◽

Amanda B. Hassinger ◽

...

Keyword(s):

Serum Creatinine ◽

Renal Dysfunction ◽

Critically Ill ◽

Urine Output ◽

Data Extraction ◽

Case Series ◽

Adverse Outcomes ◽

Assessment Tools ◽

Current Evidence ◽

Critically Ill Children

CONTEXT Renal dysfunction is associated with poor outcomes in critically ill children. OBJECTIVE To evaluate the current evidence for criteria defining renal dysfunction in critically ill children and association with adverse outcomes. To develop contemporary consensus criteria for renal dysfunction in critically ill children. DATA SOURCES PubMed and Embase were searched from January 1992 to January 2020. STUDY SELECTION Included studies evaluated critically ill children with renal dysfunction, performance characteristics of assessment tools for renal dysfunction, and outcomes related to mortality, functional status, or organ-specific or other patient-centered outcomes. Studies with adults or premature infants (≤36 weeks' gestational age), animal studies, reviews, case series, and studies not published in English with inability to determine eligibility criteria were excluded. DATA EXTRACTION Data were extracted from included studies into a standard data extraction form by task force members. RESULTS The systematic review supported the following criteria for renal dysfunction: (1) urine output <0.5 mL/kg per hour for ≥6 hours and serum creatinine increase of 1.5 to 1.9 times baseline or ≥0.3 mg/dL, or (2) urine output <0.5 mL/kg per hour for ≥12 hours, or (3) serum creatinine increase ≥2 times baseline, or (4) estimated glomerular filtration rate <35 mL/minute/1.73 m2, or (5) initiation of renal replacement therapy, or (6) fluid overload ≥20%. Data also support criteria for persistent renal dysfunction and for high risk of renal dysfunction. LIMITATIONS All included studies were observational and many were retrospective. CONCLUSIONS We present consensus criteria for renal dysfunction in critically ill children.

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Adverse Outcomes due to Aggressive Fluid Resuscitation in Children: A Prospective Observational Study

Journal of Pediatric Intensive Care ◽

10.1055/s-0038-1667009 ◽

2018 ◽

Vol 08 (02) ◽

pp. 064-070 ◽

Cited By ~ 2

Author(s):

Anand Muttath ◽

Lalitha Annayappa Venkatesh ◽

Joe Jose ◽

Anil Vasudevan ◽

Santu Ghosh

Keyword(s):

Observational Study ◽

Critically Ill ◽

Prospective Observational Study ◽

Fluid Overload ◽

Fluid Management ◽

Oxygenation Index ◽

Adverse Outcomes ◽

Critically Ill Children ◽

Mortality And Morbidity ◽

The Impact

AbstractFluid management has a major impact on the duration, severity, and outcome of critically ill children. The aim of this study was to examine the relationship between cumulative fluid overload (CFO) with mortality and morbidity in critically ill children. This was a prospective observational study wherein children (1 month–16 years) who were critically ill (with shock requiring inotropes and/or mechanically ventilated) were enrolled. CFO was defined as the sum of daily fluid balances. Daily fluid balance was calculated as a difference between fluid intake (oral and intravenous) and output (urine output, discharge from nasogastric tube) in 24 hours. Percentage of fluid overload (FO) (PFO) was calculated as the ratio of CFO with weight at admission in kilogram. The CFO and PFO at 24, 48, 72 hours and at 7 days or end of PICU stay were calculated. A total of 291 children (244 survivors and 47 non-survivors; 47% males) were included in the final analysis. A higher mortality was observed in children with higher PFO (>20% FO: 45.8% mortality vs. 14.5% < 10% FO, p < 0.01) and CFO (10.97 ± 6.4 mL/kg in survivors vs. 13.95 ± 9.6 mL/kg in non-survivors; p = 0.022) at 72 hours. A 1% increase in fluid overload was associated with 6% and 4% increase in mortality at 72 hours and 7 days, respectively. Similarly, the impact of every 1% increase in fluid overload on both ventilation (yes/no) and acute kidney injury (AKI; yes/no) were found to be significant for both parameters at 72 hours, but only AKI had significant correlation on seventh day. In the multivariate stepwise Cox's proportional hazard model for PICU stay and hospital stay, 3% (p < 0.05) and 2% (p > 0.05) increase were found for every 1% increase in fluid overload, respectively. Oxygenation index is also associated with fluid overload with the adjusted model estimated 0.27 units (95% confidence interval: 0.18–0.36) increase per 1% increase in fluid overload. FO was associated with increased mortality and morbidity in critically ill children.

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Impact of Cryopreservation and Transit Times of Allogeneic Grafts on Hematopoietic and Immune Reconstitution

Blood Advances ◽

10.1182/bloodadvances.2021005139 ◽

2021 ◽

Author(s):

Katie Maurer ◽

Haesook T Kim ◽

Thomas Michael Kuczmarski ◽

Heather M Garrity ◽

Augustine Weber ◽

...

Keyword(s):

Stem Cell ◽

Clinical Outcomes ◽

Graft Failure ◽

Immune Reconstitution ◽

White Blood Cells ◽

Adverse Outcomes ◽

T Cell Subsets ◽

Unrelated Donor ◽

Increased Risk ◽

The Impact

We sought to evaluate the impact of cryopreservation of unrelated donor peripheral blood stem cell (PBSC) grafts on engraftment, chimerism, and immune reconstitution in the context of the Covid-19 pandemic. We reviewed stem cell product characteristics and clinical outcomes in 101 patients receiving cryopreserved PBSCs from unrelated donors (URD) between January 1, 2019, and December 31, 2020, compared with 203 patients receiving fresh URD PBSCs. We observed no differences in 6-month overall survival, progression free survival, or non-relapse mortality. Patients receiving cryopreserved PBSCs had delayed platelet engraftment and impaired reconstitution of white blood cells and T cell subsets at Day 30. Thirty-four percent of patients receiving cryopreserved grafts had CD3 chimerism <50% at Day 30 after transplantation, compared with 14% of patients receiving fresh PBSCs (p=0.0002). At day 100, this difference persisted (CD3+ chimerism <50%: 17% of cryopreserved cohort vs 6% of fresh cohort, p=0.016). Additionally, greater product age at infusion is associated with an increase in graft failure, independent of cryopreservation. Receipt of grafts >48 hours old at time of cryopreservation or infusion significantly increased the risk of graft failure (sHR =4.57 (95% CI 1.71-12.3), p=0.0025). Our data indicate that cryopreservation is associated with similar overall short-term clinical outcomes compared to fresh PBSC. However, patients must be monitored closely for increased risk of other potentially adverse outcomes including graft failure and poor immune recovery, particularly for grafts with older overall age at infusion. Longer term follow-up is needed to determine impact on relapse and survival.

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Impact of the Ebola epidemic on clinical outcomes of HIV-infected soldiers and their dependents in Sierra Leone

International Journal of STD & AIDS ◽

10.1177/0956462418797843 ◽

2018 ◽

Vol 30 (2) ◽

pp. 106-112 ◽

Cited By ~ 3

Author(s):

Elizabeth Nagel ◽

Michael J Blackowicz ◽

Foday Sahr ◽

Olamide D Jarrett

Keyword(s):

Clinical Outcomes ◽

Sierra Leone ◽

Repeated Measures ◽

Disease Outbreaks ◽

Armed Forces ◽

Hiv Treatment ◽

Hiv Care ◽

Increased Risk ◽

The Republic ◽

The Impact

The impact of the 2014–2016 Ebola epidemic in West Africa on human immunodeficiency virus (HIV) treatment in Sierra Leone is unknown, especially for groups with higher HIV prevalence such as the military. Using a retrospective study design, clinical outcomes were evaluated prior to and during the epidemic for 264 HIV-infected soldiers of the Republic of Sierra Leone Armed Forces (RSLAF) and their dependents receiving HIV treatment at the primary RSLAF HIV clinic. Medical records were abstracted for baseline clinical data and clinic attendance. Estimated risk of lost to follow-up (LTFU), default, and number of days without antiretroviral therapy (DWA) were calculated using repeated measures general estimating equations adjusted for age and gender. Due to missing data, 262 patients were included in the final analyses. There was higher risk of LTFU throughout the Ebola epidemic in Sierra Leone compared to the pre-Ebola baseline, with the largest increase in LTFU risk occurring at the peak of the epidemic (relative risk: 3.22, 95% CI: 2.22–4.67). There was an increased risk of default and DWA during the Ebola epidemic for soldiers but not for their dependents. The risk of LTFU, default, and DWA stabilized once the epidemic was largely resolved but remained elevated compared to the pre-Ebola baseline. Our findings demonstrate the negative and potentially lasting impact of the Ebola epidemic on HIV care in Sierra Leone and highlight the need to develop strategies to minimize disruptions in HIV care with future disease outbreaks.

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