2024 Focused Update: Guidelines on Use of Corticosteroids in Sepsis, Acute Respiratory Distress Syndrome, and Community-Acquired Pneumonia.

RATIONALE: New evidence is available examining the use of corticosteroids in sepsis, acute respiratory distress syndrome (ARDS) and community-acquired pneumonia (CAP), warranting a focused update of the 2017 guideline on critical illness-related corticosteroid insufficiency. OBJECTIVES: To develop evidence-based recommendations for use of corticosteroids in hospitalized adults and children with sepsis, ARDS, and CAP. PANEL DESIGN: The 22-member panel included diverse representation from medicine, including adult and pediatric intensivists, pulmonologists, endocrinologists, nurses, pharmacists, and clinician-methodologists with expertise in developing evidence-based Clinical Practice Guidelines. We followed Society of Critical Care Medicine conflict of interest policies in all phases of the guideline development, including task force selection and voting. METHODS: After development of five focused Population, Intervention, Control, and Outcomes (PICO) questions, we conducted systematic reviews to identify the best available evidence addressing each question. We evaluated the certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach and formulated recommendations using the evidence-to-decision framework. RESULTS: In response to the five PICOs, the panel issued four recommendations addressing the use of corticosteroids in patients with sepsis, ARDS, and CAP. These included a conditional recommendation to administer corticosteroids for patients with septic shock and critically ill patients with ARDS and a strong recommendation for use in hospitalized patients with severe CAP. The panel also recommended against high dose/short duration administration of corticosteroids for septic shock. In response to the final PICO regarding type of corticosteroid molecule in ARDS, the panel was unable to provide specific recommendations addressing corticosteroid molecule, dose, and duration of therapy, based on currently available evidence. CONCLUSIONS: The panel provided updated recommendations based on current evidence to inform clinicians, patients, and other stakeholders on the use of corticosteroids for sepsis, ARDS, and CAP.

The concomitant use of ultra short beta-blockers with vasopressors and inotropes in critically ill patients with septic shock: A systematic review and meta-analysis of randomized controlled trials.

Background: Septic shock is associated with systemic inflammatory response, hemodynamic instability, impaired sympathetic control, and the development of multiorgan dysfunction that requires vasopressor or inotropic support. The regulation of immune function in sepsis is complex and varies over time. However, activating Beta-2 receptors and blocking Beta-1 receptors reduces the proinflammatory response by influencing cytokine production. Evidence that supports the concomitant use of ultra short beta-blockers with inotropes and vasopressors in patients with septic shock is still limited. This study aimed to evaluate the use of ultra short beta-blockers and its impact on the ICU related outcomes such as mortality, length of stay, heart rate control, shock resolution, and vasopressors/inotropes requirements. Methods: A systematic review and meta-analysis of randomized controlled trials including critically ill patients with septic shock who received inotropes and vasopressors. Patients who received either epinephrine or norepinephrine without beta-blockers "control group" were compared to patients who received ultra short beta-blockers concomitantly with either epinephrine or norepinephrine "Intervention group". MEDLINE and Embase databases were utilized to systematically search for studies investigating the use of ultra short beta-blockers in critically ill patients on either epinephrine or norepinephrine from inception to October 10, 2023. The primary outcome was the 28-day mortality. While, length of stay, heart rate control, and inotropes/ vasopressors requirements were considered secondary outcomes. Results: Among 47 potentially relevant studies, nine were included in the analysis. The 28-day mortality risk was lower in patients with septic shock who used ultra short beta-blockers concomitantly with either epinephrine or norepinephrine compared with the control group (RR (95%CI): 0.69 (0.53, 0.89), I2=26%; P=0.24). In addition, heart rate was statistically significantly lower with a standardized mean difference (SMD) of -22.39 (95% CI: -24.71, -20.06) among the beta-blockers group than the control group. The SMD for hospital length of stay and the inotropes requirement were not statistically different between the two groups (SMD (95%CI): -0.57 (-2.77, 1.64), and SMD (95%CI): 0.08 (-0.02, 0.19), respectively). Conclusion: The use of ultra short beta-blockers concomitantly with either epinephrine or norepinephrine in critically ill patients with septic shock was associated with better heart rate control and survival benefits without increment in the inotropes and vasopressors requirement.

The Reviewer Academy of the Society of Critical Care Medicine: Key Principles and Strategic Plan.

The Society of Critical Care Medicine (SCCM) Reviewer Academy seeks to train and establish a community of trusted, reliable, and skilled peer reviewers with diverse backgrounds and interests to promote high-quality reviews for each of the SCCM journals. Goals of the Academy include building accessible resources to highlight qualities of excellent manuscript reviews; educating and mentoring a diverse group of healthcare professionals; and establishing and upholding standards for insightful and informative reviews. This manuscript will map the mission of the Reviewer Academy with a succinct summary of the importance of peer review, process of reviewing a manuscript, and the expected ethical standards of reviewers. We will equip readers to target concise, thoughtful feedback as peer reviewers, advance their understanding of the editorial process and inspire readers to integrate medical journalism into diverse professional careers.

Patient diversity and author representation in clinical studies supporting the Surviving Sepsis Campaign guidelines for management of sepsis and septic shock 2021: a systematic review of citations.

BACKGROUND: The generalizability of the Surviving Sepsis Campaign (SSC) guidelines to various patient populations and hospital settings has been debated. A quantitative assessment of the diversity and representation in the clinical evidence supporting the guidelines would help evaluate the generalizability of the recommendations and identify strategic research goals and priorities. In this study, we evaluated the diversity of patients in the original studies, in terms of sex, race/ethnicity, and geographical location. We also assessed diversity in sex and geographical representation among study first and last authors. METHODS: All clinical studies cited in support of the 2021 SSC adult guideline recommendations were identified. Original clinical studies were included, while editorials, reviews, non-clinical studies, and meta-analyses were excluded. For eligible studies, we recorded the proportion of male patients, percentage of each represented racial/ethnic subgroup (when available), and countries in which they were conducted. We also recorded the sex and location of the first and last authors. The World Bank classification was used to categorize countries. RESULTS: The SSC guidelines included six sections, with 85 recommendations based on 351 clinical studies. The proportion of male patients ranged from 47 to 62%. Most studies did not report the racial/ ethnic distribution of the included patients; when they did so, most were White patients (68-77%). Most studies were conducted in high-income countries (77-99%), which included Europe/Central Asia (33-66%) and North America (36-55%). Moreover, most first/last authors were males (55-93%) and from high-income countries (77-99%). CONCLUSIONS: To enhance the generalizability of the SCC guidelines, stakeholders should define strategies to enhance the diversity and representation in clinical studies. Though there was reasonable representation in sex among patients included in clinical studies, the evidence did not reflect diversity in the race/ethnicity and geographical locations. There was also lack of diversity among the first and last authors contributing to the evidence.

All-cause mortality in cancer patients treated for sepsis in intensive care units: a systematic review and meta-analysis.

PURPOSE: Sepsis is a common complication in patients with cancer, but studies evaluating the outcomes of critically ill cancer patients with sepsis on a global scale are limited. We aimed to summarize the existing evidence on mortality rates in this patient population. METHODS: Prospective and retrospective observational studies evaluating critically ill adult cancer patients with sepsis, severe sepsis, and/or septic shock were included. Studies published from January 2010 to September 2021 that reported at least one mortality outcome were retrieved from MEDLINE (Ovid), Embase (Ovid), and Cochrane databases. Study selection, bias assessment, and data collection were performed independently by two reviewers, and any discrepancies were resolved by a third reviewer. The risk of bias was assessed using the Newcastle-Ottawa scale. We calculated pooled intensive care unit (ICU), hospital, and 28/30-day mortality rates. The heterogeneity of the data was tested using the chi-square test, with a P value < 0.10 indicating significant heterogeneity. RESULTS: A total of 5464 citations were reviewed, of which 10 studies met the inclusion criteria; these studies included 6605 patients. All studies had a Newcastle-Ottawa scale score of 7 or higher. The mean patient age ranged from 51.4 to 64.9 years. The pooled ICU, hospital, and 28/30 day mortality rates were 48% (95% CI, 43- 53%; I2 = 80.6%), 62% (95% CI, 58-67%; I2 = 0%), and 50% (95% CI, 38- 62%; I2 = 98%), respectively. Substantial between-study heterogeneity was observed. CONCLUSION: Critically ill cancer patients with sepsis had poor survival, with a hospital mortality rate of about two-thirds. The substantial observed heterogeneity among studies could be attributed to variability in the criteria used to define sepsis as well as variability in treatment, the severity of illness, and care across settings. Our results are a call to action to identify strategies that improve outcomes for cancer patients with sepsis.

A 12-year study evaluating the outcomes and predictors of mortality in critically ill cancer patients admitted with septic shock.

BACKGROUND: Though sepsis is common in patients with cancer, there are limited studies that evaluated sepsis and septic shock in this patient population. The objective of this study was to evaluate the outcomes and to identify predictors of mortality in cancer patients admitted to the intensive care unit (ICU) with septic shock. METHODS: This was a retrospective study conducted at a medical-surgical oncologic ICU of a comprehensive cancer center. Adult cancer patients admitted with septic shock between January 1, 2008 and December 31, 2019 were enrolled. Septic shock was defined as an ICU admission diagnosis of sepsis that required initiating vasopressors within 24 h of admission. Patient baseline characteristics, ICU length of stay and ICU and hospital mortality were recorded. Univariate analysis and logistic regression were performed to identify predictors associated with ICU and hospital mortality. RESULTS: During the study period, 1408 patients met the inclusion criteria. The mean age was 56.8 ± 16.1 (SD) years and mean Acute Physiology and Chronic Health Evaluation (APACHE) II was 23.0 ± 7.91 (SD). Among the enrolled patients, 67.8% had solid tumors while the remaining had hematological malignancies. Neutropenia and thrombocytopenia were reported in 19.3 and 39.5% of the patients, respectively, and mechanical ventilation was required for 42% of the patients. Positive cultures were reported in 836 (59.4%) patients, most commonly blood (33%) and respiratory (26.6%). Upon admission, about half the patients had acute kidney injury, while elevated total bilirubin and lactic acid levels were reported in 13.8 and 65.2% of the patients, respectively. The median ICU length of stay was 4 days (IQR 3-8), and ICU and hospital mortality were reported in 688 (48.9%) and 914 (64.9%) patients, respectively. Mechanical ventilation, APACHE II, thrombocytopenia, positive cultures, elevated bilirubin and lactic acid levels were significantly associated with both ICU and hospital mortality. CONCLUSIONS: In a relatively large cohort of patients with solid and hematological malignancies admitted to the ICU with septic shock, hospital mortality was reported in about two-third of the patients. Mechanical ventilation, APACHE II, thrombocytopenia, positive cultures, elevated bilirubin and lactic acid levels were significant predictors of mortality.

Impacts of a Mail-Order Service for Refilling Prescriptions on Patient Satisfaction and Operational Load at a Comprehensive Cancer Center in Jordan.

BACKGROUND: Mail-order services for refilling prescriptions for medications have been established in many countries and have increased patient satisfaction. We developed a mail-order service for the outpatient pharmacy of a comprehensive cancer center in Jordan. OBJECTIVE: To describe the implementation of a mail-order service and to report the impact of the service on patient satisfaction and the pharmacy workload. METHODS: A multidisciplinary team was formed to plan a mail-order service for refilling prescriptions for medications, and a survey was designed to evaluate patient satisfaction with the service. Patients were instructed to call the refill call center and order their medications at least 48 hours before their refill is due. The pharmacy workflow for refilling prescriptions was evaluated, and the time required with and without the mail-order service was documented, with a calculation of the time saved. RESULTS: At 1 year after the mail-order service had been established, 14 200 prescriptions had been refilled through the service, with the majority (97.5%) dispensed within 48 hours of the order time. As per the survey conducted with 219 patients, on the overall satisfaction, 69.4% reported being highly satisfied with the service and 27.9% reported being satisfied. The problems reported with the service were delay in arrival (n = 23, 10.5%), medication-related errors (n = 9, 4.1%), cash-related error (n = 1, 0.45%), improper storage condition (n = 1, 0.45%), and delivery to the wrong address (n = 4, 1.8%). The service was also associated with reduced overall time for processing in the outpatient pharmacy service; for patients receiving their medications from the pharmacy, resulting in reduced patients' overall waiting time (from 11.4 to 8.2 minutes). The service resulted in saving of 0.4 full-time employee at 1 year of implementation. CONCLUSIONS: A mail-order service for refilling prescriptions within a hospital setting had positive outcomes on both patient satisfaction and the pharmacy workflow. The major issues were related to transportation and logistics.

The Impact of Lean Management Implementation on Waiting Time and Satisfaction of Patients and Staff at an Outpatient Pharmacy of a Comprehensive Cancer Center in Jordan.

Background: Patient satisfaction with outpatient pharmacy services at our institution was below the target level, due mainly to long waiting times. A lean management strategy to reduce patient waiting time and increase the satisfaction of both patients and staff was developed and implemented. Methods: The project was conducted in the outpatient pharmacy of a comprehensive cancer center in Amman, Jordan. The process started with formation of a multidisciplinary team and A3 problem-solving, which is a 10-step scientific method with measurable patient-centered outcomes. Average patient waiting time and level of patient satisfaction were compared before and after full implementation of the process. In addition, a survey was conducted among the pharmacy staff who worked in the outpatient pharmacy during the process to determine its impact on staff satisfaction. Results: Patient waiting time for prescriptions of fewer than 3 medications and of 3 medications or more decreased significantly (22.3 minutes vs 8.1 minutes, P < .001, and 31.8 minutes vs 16.1 minutes, P < .002, respectively), and patient satisfaction increased (62% vs 69%; P = .005) after full implementation of the project. The majority of the pharmacy staff reported that the process motivated them in their work and that both their jobs and their relationships with their managers and colleagues had improved. Conclusion: Application of lean management in an outpatient pharmacy was effective in reducing patient waiting time and improving the satisfaction of both patients and employees.

Variation in Fluid and Vasopressor Use in Shock With and Without Physiologic Assessment: A Multicenter Observational Study.

OBJECTIVES: To characterize the association between the use of physiologic assessment (central venous pressure, pulmonary artery occlusion pressure, stroke volume variation, pulse pressure variation, passive leg raise test, and critical care ultrasound) with fluid and vasopressor administration 24 hours after shock onset and with in-hospital mortality. DESIGN: Multicenter prospective cohort study between September 2017 and February 2018. SETTINGS: Thirty-four hospitals in the United States and Jordan. PATIENTS: Consecutive adult patients requiring admission to the ICU with systolic blood pressure less than or equal to 90 mm Hg, mean arterial blood pressure less than or equal to 65 mm Hg, or need for vasopressor. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Of 1,639 patients enrolled, 39% had physiologic assessments. Use of physiologic assessment was not associated with cumulative fluid administered within 24 hours of shock onset, after accounting for baseline characteristics, etiology and location of shock, ICU types, Acute Physiology and Chronic Health Evaluation III, and hospital (beta coefficient, 0.04; 95% CI, -0.07 to 0.15). In multivariate analysis, the use of physiologic assessment was associated with a higher likelihood of vasopressor use (adjusted odds ratio, 1.98; 95% CI, 1.45-2.71) and higher 24-hour cumulative vasopressor dosing as norepinephrine equivalent (beta coefficient, 0.37; 95% CI, 0.19-0.55). The use of vasopressor was associated with increased odds of in-hospital mortality (adjusted odds ratio, 1.88; 95% CI, 1.27-2.78). In-hospital mortality was not associated with the use of physiologic assessment (adjusted odds ratio, 0.86; 95% CI, 0.63-1.18). CONCLUSIONS: The use of physiologic assessment in the 24 hours after shock onset is associated with increased use of vasopressor but not with fluid administration.

Evaluation of Vasopressor Exposure and Mortality in Patients With Septic Shock.

OBJECTIVES: The objectives of this study were to: 1) determine the association between vasopressor dosing intensity during the first 6 hours and first 24 hours after the onset of septic shock and 30-day in-hospital mortality; 2) determine whether the effect of vasopressor dosing intensity varies by fluid resuscitation volume; and 3) determine whether the effect of vasopressor dosing intensity varies by dosing titration pattern. DESIGN: Multicenter prospective cohort study between September 2017 and February 2018. Vasopressor dosing intensity was defined as the total vasopressor dose infused across all vasopressors in norepinephrine equivalents. SETTING: Thirty-three hospital sites in the United States (n = 32) and Jordan (n = 1). PATIENTS: Consecutive adults requiring admission to the ICU with septic shock treated with greater than or equal to 1 vasopressor within 24 hours of shock onset. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Out of 1,639 patients screened, 616 were included. Norepinephrine (93%) was the most common vasopressor. Patients received a median of 3,400 mL (interquartile range, 1,851-5,338 mL) during the 24 hours after shock diagnosis. The median vasopressor dosing intensity during the first 24 hours of shock onset was 8.5 µg/min norepinephrine equivalents (3.4-18.1 µg/min norepinephrine equivalents). In the first 6 hours, increasing vasopressor dosing intensity was associated with increased odds ratio of 30-day in-hospital mortality, with the strength of association dependent on concomitant fluid administration. Over the entire 24 hour period, every 10 µg/min increase in vasopressor dosing intensity was associated with an increased risk of 30-day mortality (adjusted odds ratio, 1.33; 95% CI, 1.16-1.53), and this association did not vary with the amount of fluid administration. Compared to an early high/late low vasopressor dosing strategy, an early low/late high or sustained high vasopressor dosing strategy was associated with higher mortality. CONCLUSIONS: Increasing vasopressor dosing intensity during the first 24 hours after septic shock was associated with increased mortality. This association varied with the amount of early fluid administration and the timing of vasopressor titration.

Evaluating the Predictive Value of Lactate in Patients With Cancer Having Septic Shock.

PURPOSE: Limited studies evaluated the predictive value of serum lactate (LA) in critically ill patients with cancer. The main objective of this study was to evaluate the predictive validity of LA single measurements as well as LA clearance in predicting mortality in patients with cancer having septic shock. The study also aimed to determine the LA measurement over the first 24 hours with the highest predictability for hospital mortality. MATERIALS AND METHODS: A retrospective cohort study of adult patients with cancer having septic shock and LA measurements during the first 24 hours. Three receiver-operating characteristic (ROC) curves were constructed to evaluate the predictive validity for hospital mortality of LA at baseline, at 6 hours and at 24 hours after identifying septic shock. The ROC with the largest area under the curve was analyzed to determine LA level with the highest predictability for hospital mortality. In addition, the ability of LA normalization (LA <2 mmol/L at 6 hours and at 24 hours) and the degree of LA elimination (>10% and >20% at 24 hours) to predict hospital mortality were evaluated by determining the predictive values for each clearance end point. RESULTS: The study included 401 patients. LA >2.5 mmol/L at 24 hours showed the largest area under the ROC curve to predict hospital mortality (ROC area: 0.648; 95% confidence interval: 0.585-0.711) with a sensitivity of 58.4% and specificity of 62.8%. The LA normalization, LA clearance >10%, and LA clearance >20% were also predictors of hospital mortality, with the highest sensitivity for LA normalization at 6 hours (74%) and LA normalization at 24 hours (73.4%). CONCLUSION: In patients with cancer having septic shock, LA >2.5 mmol/L at 24 hours of septic shock had the highest predictability for hospital mortality. The LA normalization and clearance were also predictors of hospital mortality. However, all LA end points were not strong predictors.

Critical Review of Double-Carbapenem Therapy for the Treatment of Carbapenemase-Producing Klebsiella pneumoniae.

OBJECTIVE: To review the clinical data on the effectiveness and safety of double carbapenem therapy (DCT) in patients infected with carbapenemase-producing Klebsiella pneumoniae (CP-Kp). DATA SOURCES: A literature search was performed utilizing PubMed and EMBASE (from 1966 to May 2018); bibliographies of the retrieved articles were also searched. STUDY SELECTION AND DATA EXTRACTION: Articles were included if they evaluated patients with infections caused by CP-Kp and were treated with DCT. Meeting abstracts, editorials, and animal and in vitro studies were excluded. DATA SYNTHESIS: The search strategy revealed 8 case reports and 6 clinical studies (total of 171 patients) that evaluated the administration of ertapenem followed by prolonged infusions of meropenem or doripenem. Most patients were critically ill and commonly had infections in the blood, lungs, and urine. Clinical and microbiological success were reported in 70% of the patients and mortality in 24%. Adverse events, which included mostly seizures, sodium disorders, and gastrointestinal symptoms, were reported in 16 patients; none required interruption of treatment. Relevance to Patient Care and Clinical Practice: This review evaluated the clinical experience of DCT in the treatment of CP-Kp infections, based on case reports and clinical studies, for the potential role of DCT as a therapeutic option. CONCLUSION: Despite the limited studies, current data suggest that DCT may be an effective and safe strategy to treat CP-Kp. However, large randomized controlled trials are necessary to clearly define the role of DCT.

Fixed-dose combination associated with faster time to smear conversion compared to separate tablets of anti-tuberculosis drugs in patients with poorly controlled diabetes and pulmonary tuberculosis in Qatar.

BACKGROUND: Diabetes is associated with increased risk of tuberculosis (TB) treatment failure, death, and relapse compared to patients without diabetes. Current TB regimens are available as fixed dose combination (FDC) and separate tablets (ST), in which using the former is purported to make it easier to adhere and complete treatment. So far there are no studies assessing the performance of FDC compared to ST in diabetic patients with pulmonary TB. METHODOLOGY: A retrospective cohort study was conducted, and included eight hospitals in Qatar in which patients diagnosed with pulmonary TB received rifampin, isoniazid, pyrazinamide, and ethambutol (as FDC or ST) given as directly observed therapy. Sputum smears for acid fast bacilli were tested weekly. We included patients admitted between December 2012 and December 2015, ≥18 years old, diagnosed with TB with pretreatment positive sputum smears, and having diabetes. Patients with Mycobacterium tuberculosis that was resistant to any first-line drug were excluded. Blood glucose was monitored closely and controlled to < 180 md/dL using oral hypoglycemic agents and/or insulin. We assessed the effectiveness of TB regimens by comparing time to confirmed negative smears between those treated with FDC or ST, and the impact of adding metformin. RESULTS: 103 patients met inclusion criteria. Mean age and body mass index were 45.6 ± 9.1 years and 22.1 ± 3.6 kg/m2, respectively. Fifty-four (52%) patients received the FDC. There was no difference between groups in baseline characteristics and sputum bacillary loads. Patients prescribed FDC showed faster times to sputum smear conversion compared to ST (32 ± 19 vs. 46 ± 31 days, p = 0.01). The difference was greater among patients with pretreatment bacillary load of 3+ (FDC 36.6 ± 19.5 vs. ST 56.1 ± 28.8, p = 0.008). Receipt of metformin≥2000 mg/day altered the difference in time to smear conversion (FDC 30.7 ± 13.4 vs. ST 62 ± 35.5, p = 0.016), which was of greatest difference in those with pretreatment bacillary load 3+ and who received metformin≥2000 mg/day (FDC 36 ± 12.1 vs. ST 92.2 ± 26 days, p = 0.001). CONCLUSION: Patients with diabetes and prescribed FDC showed faster smear conversion during treatment for pulmonary TB compared to ST which was more pronounced in those with 3+ bacillary load pretreatment and which appeared to be modified by higher dose metformin.

The impact of pharmacist telephone calls after discharge on satisfaction of oncology patients: A randomized controlled study.

Purpose The aim of the study was to determine the impact of telephone follow-up calls on satisfaction in oncology patients after hospital discharge. Method A randomized controlled study, in which patients were randomized into two groups: The experimental group with the telephone follow-up (TFU) calls (intervention) and the control group (no intervention). The telephone follow-up call was conducted within 72 h after discharge. During the call, patients were asked about their medications, namely, whether they received them, understood how to take them, and whether they developed any medication-related adverse effect. Both groups were contacted by phone two weeks later to assess their satisfaction with the discharge medication instructions and the provided pharmaceutical services, using the 5-point Likert scale. In addition, hospital records were reviewed for emergency room visits and hospital readmissions within 30 days after discharge. Results There was no difference in the percentage of patients who reported being very satisfied between both the intervention and the control groups (45% intervention vs. 48% control, P = 0.68). The mean time of the intervention phone call was 3 ± 1.7 (SD) min. During the telephone follow-up call, medication-related problems were identified in 20% of the patients. There was no significant difference in emergency room visits and hospital readmissions in the intervention group vs. control (44% vs. 53%, P = 0.123) and (37% vs. 43%, P = 0.317), respectively. Conclusion Telephone follow-up calls conducted by a pharmacist to discharged oncology patients did not improve patients' satisfaction, emergency room visits or hospital readmissions; however, they helped to identify medication-related adverse effects in the oncology patients.

Augmented Renal Clearance Using Population-Based Pharmacokinetic Modeling in Critically Ill Pediatric Patients.

OBJECTIVES: The objectives of this study were to: 1) evaluate the prevalence of augmented renal clearance in critically ill pediatric patients using vancomycin clearance; 2) derive the pharmacokinetic model that best describes vancomycin clearance in critically ill pediatric patients; and 3) correlate vancomycin clearance with creatinine clearance estimated by modified Schwartz or Cockcroft-Gault. DESIGN: Retrospective, two-center, cohort study from 2003 to 2016. SETTING: Clinical drug monitoring services in the PICUs at two tertiary care, teaching hospitals. PATIENTS: Children from 1 to 21 years old. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Identify patients with augmented renal clearance (vancomycin clearance ≥ 130 mL/min/1.73 m used as definition of augmented renal clearance). Derive final population-based pharmacokinetic model and estimate individual patient pharmacokinetic parameters. Compare estimated glomerular filtration rate (modified Schwartz or Cockcroft-Gault depending on age < or ≥ 17 yr) with vancomycin clearance. Augmented renal clearance was identified in 12% of 250 total subjects. The final population-based pharmacokinetic model for vancomycin clearance (L/hr) was 0.118 × weight (e). Median vancomycin clearance in those with versus without augmented renal clearance were 141.3 and 91.7 mL/min/1.73 m, respectively (p < 0.001). By classification and regression tree analysis, patients who were more than 7.9 years old were significantly more likely to experience augmented renal clearance (17% vs 4.6% in those ≤ 7.9 yr old; p = 0.002). In patients with augmented renal clearance, 79% of 29 had vancomycin trough concentrations less than 10 µg/mL, compared with 52% of 221 in those without augmented renal clearance (p < 0.001). Vancomycin clearance was weakly correlated to the glomerular filtration rate estimated by the modified Schwartz or Cockcroft-Gault method (Spearman R = 0.083). CONCLUSIONS: Augmented renal clearance was identified in one of 10 critically ill pediatric patients using vancomycin clearance, with an increase of approximately 50 mL/min/1.73 m in those with augmented renal clearance. As augmented renal clearance results in subtherapeutic antibiotic concentrations, optimal dosing is essential in those exhibiting augmented renal clearance.

Predictors of ICU Admission in Patients With Cancer and the Related Characteristics and Outcomes: A 5-Year Registry-Based Study.

OBJECTIVE: To identify factors predictive of admission of patients with cancer to an ICU. In addition, the study aimed to describe the characteristics and outcomes, both short-term and long-term, of patients with cancer admitted to the ICU. DESIGN: Retrospective case-control study, utilizing the institution's cancer registry. SETTING: Comprehensive cancer center. PATIENTS: Patients with cancer. The case group consisted of patients who required ICU admission during the study period, whereas the control group consisted of patients who did not require ICU admission. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: The patient characteristics and outcomes were recorded. Univariate and multivariate analyses were conducted to determine factors associated with ICU admission. The registry included 10,792 patients, and among those, 2,439 patients (22.6%) required ICU admission after a median of 10.1 months (interquartile range, 3.28-25.2). The following factors were associated with ICU admission: hematologic malignancy (odds ratio, 1.51; 95% CI, 1.26-1.81), chemotherapy (odds ratio, 1.74; 95% CI, 1.48-2.03), advanced cancer (odds ratio, 2.57; 95% CI, 1.44-4.60), and smoking (odds ratio, 1.38; 95% CI, 1.20-1.61). The most common ICU admission diagnoses were sepsis (21.5%) and respiratory insufficiency/failure (25.7%). The ICU mortality was 36.5%, whereas the 1-year and 5-year survival rates were 22.8% and 14.2%, respectively. CONCLUSION: In a comprehensive cancer center, about one fourth of the patients required ICU admission. Addressing modifiable risk factors associated with ICU admission is essential to potentially reduce ICU admissions and improve long-term survival.

Vancomycin pharmacokinetics and predicted dosage requirements in pediatric cancer patients.

PURPOSE: To determine the pharmacokinetic parameters and compare pharmacodynamic target attainment at different dosing strategies of vancomycin in pediatric cancer patients. METHODS: Pediatric patients who received vancomycin and had at least two steady-state concentrations taken within the same dosing interval were identified. Vancomycin minimum inhibitory concentrations (MICs) for methicillin resistant staphylococcus aureus (MRSA) isolates from our institution were determined using E-test. The population-based pharmacokinetic modeling was performed using NONMEM 7.2. A one-compartment model with first-order kinetics was used to estimate clearance (CL) and volume of distribution (Vd). Monte Carlo simulations (N = 9800) were performed to compare area-under-the-curve over 24 h (AUC24)/MIC and trough concentration at different doses. RESULTS: Forty-nine patients, with 120 vancomcyin serum concentrations, were included in the analysis, mean age was 6 ± 2.5 (SD) years, mean weight was 19.6 ± 6.9(SD) kg, mean baseline serum creatinine was 0.4 ± 0.11(SD) mg/dl, and mean initial vancomycin dose was 205 mg/day (range 100-460). Final model pharmacokinetic parameters were: CL (L/h) = 0.381 × weight(0.75) and Vd (L) = 0.663 × weight. Mean baseline (±SD) vancomycin CL was 0.20 ± 0.07 L/h/kg and Vd 0.66 ± 0.001 L/kg. . Renal function, sex, age, stay in the intensive care unit, and co-administration of nephrotoxic medications did not have an effect on the calculated parameters. Using Monte Carlo simulation with reported MICs, a dose of 60 mg/kg/day achieved AUC24/MIC ≥400 and trough concentration ≥15 mcg/mL in only 21.5% and 11% of virtual subjects, respectively. CONCLUSIONS: Higher than usual vancomycin doses may be required to treat serious MRSA infections in pediatric patients. The currently recommended dose of 60 mg/kg/day is unlikely to achieve the targets in most subjects. The optimal vancomycin dosing in pediatric cancer patients requires further investigations.

Evaluating the effectiveness and safety of hydrocortisone therapy in cancer patients with septic shock.

PURPOSE: To evaluate the effectiveness and safety of hydrocortisone (HC) in cancer patients with septic shock. METHODS: This was a retrospective study of adult cancer patients with septic shock who received low-dose HC therapy (200 mg/day). The effectiveness of HC was assessed by determining the proportion of patients with reversal of septic shock, time to reversal, and mortality. The safety was assessed by determining the incidences of hyperglycemia, hypernatremia, and secondary infections, using a case-control approach. RESULTS: During the study period, 96 patients were enrolled. Reversal of septic shock was reported in 46 (47.9%) patients, median time to reversal was 1.9 days (range 0.2-7.6), ICU mortality was reported in 62 (65.26%) patients, and 28-day mortality in 64 (66.7%) patients. The incidence of secondary infections was higher in patients who received HC therapy, compared to patients who did not receive HC during septic shock: 44.8% vs 27.4%, P = 0.028. CONCLUSIONS: HC therapy was associated with resolution of septic shock in about half of the patients and a high incidence of secondary infections. Prospective studies are needed to fully assess the efficacy and safety of HC in cancer patients with septic shock.

Rifampicin as adjunct to colistin therapy in the treatment of multidrug-resistant Acinetobacter baumannii.

OBJECTIVE: To evaluate the available evidence regarding the efficacy and safety of rifampicin, as adjunct to colistin, in the treatment of multidrug resistant Acinetobacter baumannii (MDR-AB). DATA SOURCES: We searched MEDLINE (1966 to January 2014) using the following search terms: A baumannii, drug resistance, treatment, colistin, and rifampicin and combinations. In addition, the bibliographies of relevant articles were searched for additional citations. STUDY SELECTION AND DATA EXTRACTION: The search was limited to English-language references and adults. Studies in which colistin was not administered intravenously were excluded. In addition, we excluded meeting abstracts and single case reports. DATA SYNTHESIS: The search strategy identified 5 observational studies and 2 randomized controlled trials that evaluated the combination of intravenous colistin and rifampicin for the treatment of MDR-AB. All observational studies included a small sample size, and the microbiological clearance associated with the combination therapy ranged from 60% to 100%. The randomized controlled trials reported reduced time to microbiological clearance and higher microbiological eradication rate in the colistin/rifampicin group compared with colistin alone. However, there was no difference between both groups in the overall mortality, infection-related mortality, and the length of stay. Furthermore, rifampicin was associated with a higher incidence of hepatotoxicity. CONCLUSIONS: Studies evaluating the combination of rifampicin and colistin in the treatment of MDR-AB are limited. The currently available evidence does not support the addition of rifampicin to colistin because of the lack of improved clinical outcomes with the combination therapy and the risk of rifampicin-induced hepatotoxicity.