Enhanced recovery after surgery (ERAS® ) Society abdominal and thoracic surgery recommendations: A systematic review and comparison of guidelines for perioperative and pharmacotherapy core items.

INTRODUCTION: Worldwide, ERAS® Society guidelines have ushered in a new era of perioperative care. The purpose of this systematic review is to compare published core elements and pharmacotherapy recommendations embedded within ERAS® Society abdominal and thoracic surgery (ATS) guidelines. Determining whether a consensus exists for pharmacological core items would make future guideline preparation for similar surgeries more standardized and could improve patient care by reducing unnecessary protocol variations. METHODS: From the ERAS® Society website as of May 2023, 16 current ERAS® published ATS guidelines were included in the analysis to determine consensus and differing statements regarding each ERAS® perioperative and pharmacotherapy-related item. The aims were to (a) determine whether a consensus for each item could be derived, (b) identify gaps in ERAS® protocol development, and (c) propose potential research directions for addressing the identified gaps in the literature. RESULTS: Core items with consensus included: preoperative smoking and alcohol cessation; avoiding bowel reparation and fasting; multimodal preanesthetic, perioperative analgesia, and postoperative nausea and vomiting regimens; low molecular weight heparins for in-hospital and at-home venous thromboembolism prophylaxis; antibiotic prophylaxis; skin preparation; goal-directed perioperative fluid management with balanced crystalloids; perioperative nutrition care; ileus prevention with peripherally-acting mu receptor antagonists; and glucose control. CONCLUSION: While consensus was found for aspects of 21 current ERAS® guideline core items related to pharmacotherapy choice, details related to doses, regimen, timing of administration as well as unique aspects pertaining to specific surgeries remain to be researched and harmonized to promote guideline consistency and further optimize patient outcomes.

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.

Hemodynamic Effects of Propofol and Dexmedetomidine in Septic Patients Without Shock.

Background: Use of nonbenzodiazepine agents propofol and dexmedetomidine are first line for sedation in the intensive care unit (ICU). These agents have been implicated in the development of bradycardia and hypotension in critical illness. Objectives: To compare the development of clinically significant hypotension and/or bradycardia (ie, negative hemodynamic event) in adults with sepsis yet to require vasopressors receiving either propofol or dexmedetomidine for continuous sedation. Methods: This was a retrospective multicenter cohort study of adults with non-vasopressor-dependent sepsis admitted to an ICU at two academic medical centers between July 2013-September 2017. Results: Patients in the propofol (n = 64) and dexmedetomidine (n = 31) groups developed a clinically significant negative hemodynamic event at statistically similar frequencies (34.4% vs 16.1%, P = 0.065). Patients receiving propofol developed a larger degree of hypotension (47.3 vs 34.7 mm Hg reduction, P = 0.031). In multivariable logistic regression modeling, independent predictors of a negative hemodynamic event were a past medical history of chronic kidney disease (odds ratio [OR] = 3.8; 95% CI = 1.17-12.2; P = 0.027) and baseline heart rate (OR = 1.02; 95% CI = 1.00-1.10; P = 0.036). Conclusions and Relevance: A minority of patients with sepsis who received either propofol or dexmedetomidine experienced an event. Patients with sepsis without shock receiving continuous infusions of propofol and dexmedetomidine experienced a negative hemodynamic event at similar frequencies, though the degree of hypotension seen with propofol was greater. The clinical significance of these adverse effects requires cautious use in sepsis and further investigation.

Effects From Continuous Infusions of Dexmedetomidine and Propofol on Hemodynamic Stability in Critically Ill Adult Patients With Septic Shock.

PURPOSE: To compare the development of clinically significant hemodynamic event (ie, hypotension or bradycardia) in adults with septic shock receiving either propofol or dexmedetomidine. MATERIALS AND METHODS: A retrospective cohort study of adults with septic shock admitted to an intensive care unit (ICU) at an academic medical center between July 2013 and July 2017. RESULTS: Patients in the propofol (n = 35) and dexmedetomidine (n = 37) groups developed a clinically significant hemodynamic event at similar frequencies (31.4 vs 29.7%, P = .99). All patients with an event experienced hypotension, whereas 2 (5.4%) patients in the dexmedetomidine group also experienced bradycardia. Most patients in both groups (70% vs 90%) received an escalating sedative dose, and almost half (42.9%) in the dexmedetomidine group had the sedative dosage increased more frequently than every 30 minutes. Patients in both groups had similar ICU (24.1 vs 24.3 days, P = .98) and hospital (37.9 vs 29.7 days, P = .29) lengths of stay. There was no difference in median time to hemodynamic event between the groups (propofol 1 hour [interquartile range, IQR: 0.5-9.9] vs dexmedetomidine 2 hours [IQR: 1.5-11.1 hours], P = .85). CONCLUSION: Patients with septic shock receiving propofol or dexmedetomidine experienced similar rates of clinically significant hemodynamic events. Most patients did not experience an event and those who did most frequently did so in the first couple of hours of therapy.

Norepinephrine and Vasopressin Compared With Norepinephrine and Epinephrine in Adults With Septic Shock.

Background: The optimal adjuvant vasopressor to norepinephrine in septic shock remains controversial. Objective: To compare durations of shock-free survival between adjuvant vasopressin and epinephrine. Methods: A retrospective, single-center, matched cohort study of adults with septic shock refractory to norepinephrine was conducted. Patients receiving norepinephrine not at target mean arterial pressure (MAP; 65 mm Hg) were initiated on vasopressin or epinephrine to raise MAP to target. Vasopressin-exposed patients were matched to epinephrine-exposed patients using propensity scores. Mortality outcomes were examined using multivariable Poisson regression with robust variance estimation. Results: Of 166 patients, 96 (entire cohort) were included in the propensity score-matched cohort. Shock-free survival durations in the first 7 days were similar between epinephrine- and vasopressin-exposed patients in the matched cohort (median = 13.2 hours, interquartile range [IQR] = 0-121.0, vs median = 41.3 hours, IQR = 0-125.9; P = 0.51). Seven- and 28-day mortality rates were similar in the matched cohort (7-day: 47.9% vs 39.6%, P = 0.35; 28-day: 56.3% vs 58.3%, P = 0.84). Mortality rates were similar between epinephrine- and vasopressin-exposed patients in propensity score-matched regression models with and without adjustments at 7 (relative risk [RR] = 1.28, 95% CI = 0.92-1.79; RR = 1.21, 95% CI = 0.81-1.81) and 28 days (RR = 1.04, 95% CI = 0.81-1.34; RR = 0.96, 95% CI = 0.69-1.34). Conclusion and Relevance: Shock-free survival durations were similar in matched epinephrine- and vasopressin-exposed groups. Adjuvant epinephrine or vasopressin alongside norepinephrine to raise MAP to target requires further investigation.

Validation of a Host Response Assay, SeptiCyte LAB, for Discriminating Sepsis from Systemic Inflammatory Response Syndrome in the ICU.

RATIONALE: A molecular test to distinguish between sepsis and systemic inflammation of noninfectious etiology could potentially have clinical utility. OBJECTIVES: This study evaluated the diagnostic performance of a molecular host response assay (SeptiCyte LAB) designed to distinguish between sepsis and noninfectious systemic inflammation in critically ill adults. METHODS: The study employed a prospective, observational, noninterventional design and recruited a heterogeneous cohort of adult critical care patients from seven sites in the United States (n = 249). An additional group of 198 patients, recruited in the large MARS (Molecular Diagnosis and Risk Stratification of Sepsis) consortium trial in the Netherlands ( www.clinicaltrials.gov identifier NCT01905033), was also tested and analyzed, making a grand total of 447 patients in our study. The performance of SeptiCyte LAB was compared with retrospective physician diagnosis by a panel of three experts. MEASUREMENTS AND MAIN RESULTS: In receiver operating characteristic curve analysis, SeptiCyte LAB had an estimated area under the curve of 0.82-0.89 for discriminating sepsis from noninfectious systemic inflammation. The relative likelihood of sepsis versus noninfectious systemic inflammation was found to increase with increasing test score (range, 0-10). In a forward logistic regression analysis, the diagnostic performance of the assay was improved only marginally when used in combination with other clinical and laboratory variables, including procalcitonin. The performance of the assay was not significantly affected by demographic variables, including age, sex, or race/ethnicity. CONCLUSIONS: SeptiCyte LAB appears to be a promising diagnostic tool to complement physician assessment of infection likelihood in critically ill adult patients with systemic inflammation. Clinical trial registered with www.clinicaltrials.gov (NCT01905033 and NCT02127502).

Effects of Chronic Antihypertensives on Vasopressor Dosing in Septic Shock.

BACKGROUND: In septic shock, chronic antihypertensive medications are held acutely. Vasopressors are often required to maintain blood pressure. The effect of chronic exposure to antihypertensive therapies on vasopressor dosing in septic shock is not known. OBJECTIVE: To determine the effects of chronic exposure to antihypertensive therapies, specifically ß-blockers and angiotensin-converting enzyme (ACE) inhibitors, on cumulative vasopressor dosing in septic shock. METHODS: This was a retrospective cohort review, with data collected from routine care. Patients admitted to the medical intensive care unit with septic shock and vasopressor use were included and divided into 4 groups based on chronic medication use: (1) no ß-blocker or ACE inhibitor, (2) ß-blocker only, (3) ACE inhibitor only, and (4) ß-blocker and ACE inhibitor. Cumulative vasopressor dose at 48 hours was assessed. Demographics, comorbid conditions, suspected site of infection, disease severity, mortality, and concomitant therapies were evaluated between groups. RESULTS: A total of 133 patients with septic shock treated with vasopressors were included. No difference in cumulative vasopressor dose at 48 hours was detected between the 4 groups, respectively (median norepinephrine milligram equivalents [interquartile range (IQR)]: no ß-blocker or ACE inhibitor, 13.7 mg [6.0-35.7]; ß-blocker only, 13.1 mg [5.4-23.9]; ACE inhibitor only, 13.2 mg [1.2-36.7]; ß-blocker and ACE inhibitor, 11.3 mg [4.7-42.9]; P = 0.669). Total time on vasopressors differed between groups (median hours [IQR]: no ß-blocker or ACE inhibitor, 30h [17-60]; ß-blocker only, 24h [10-69]; ACE inhibitor only, 19h [6-25]; ß-blocker and ACE inhibitor, 30h [15-58]; P = 0.031). Comorbid conditions, suspected infection sites, disease severity, mortality, and concomitant therapies were similar. CONCLUSIONS: Chronic ß-blocker, ACE inhibitor use, or the combination of both did not affect cumulative vasopressor dose at 48 hours in septic shock. However, prior-to-admission medications may affect total time of vasopressor use.

Determining the Clinical Utility of an Absolute Procalcitonin Value for Predicting a Positive Culture Result.

Various procalcitonin ranges have been established to guide antimicrobial therapy; however, there are no data that establish whether the initial procalcitonin value can determine the likelihood of a positive culture result. This study aimed to establish if the initial procalcitonin value, on clinical presentation, has a positive predictive value for any positive culture result. This was a retrospective study of 813 medical intensive care unit patients. Data collected included patient demographics, procalcitonin assay results, sources of infection, culture results, and lengths of stay. Patients were excluded if they were immunocompromised. The primary outcome of this study was to determine a procalcitonin value that would predict any positive culture. Secondary outcomes included the sensitivity, specificity, positive predictive value, and negative predictive value for procalcitonin. After exclusions, a total of 519 patient charts were reviewed to determine the impact of the initial procalcitonin value on culture positivity. In our analyses, the receiver operating characteristic values were 0.62 for all cultures, 0.49 for pulmonary infections, 0.43 for urinary tract infections, and 0.78 for bacteremia. A procalcitonin value of 3.61 ng/ml was determined to be the threshold value for a positive blood culture result (prevalence, 4%). For bacteremia, the sensitivity of procalcitonin was 75%, the specificity was 72%, the positive predictive value was 20%, and the negative predictive value was 97%. Procalcitonin was a poor predictor of culture positivity. An initial procalcitonin value of less than 3.61 ng/ml may be useful in predicting whether bacteremia is absent. Procalcitonin should not be used as the only predictor for determining initiation of antibiotic therapy.

Efficacy and safety of tranexamic acid versus ϵ-aminocaproic acid in cardiovascular surgery.

BACKGROUND: Blood conservation is a major concern in the management of surgical patients because of transfusion-related complications, limited supply, and health care costs. Tranexamic acid (TXA) and ϵ-aminocaproic acid (ϵACA) are lysine analogue antifibrinolytics used to reduce surgical bleeding and transfusions. OBJECTIVE: To evaluate the efficacy and safety of TXA compared with ϵACA in the management of cardiovascular surgical bleeding at an academic medical center. METHODS: This single-center, retrospective, observational cohort study included 120 patients undergoing cardiovascular surgery with or without cardiopulmonary bypass, who received at least 1 dose of perioperative TXA or ϵACA. The efficacy outcome-massive perioperative bleeding-was a composite end point of chest tube drainage >1500 mL in any 8-hour period after surgery, perioperative transfusion of 10 or more units of packed red blood cells, reoperation for bleeding, or death from hemorrhage within 30 days. The safety outcomes were incidence of thromboembolic events, postoperative renal dysfunction, seizure, and 30-day all-cause mortality. RESULTS: The primary end point-massive perioperative bleeding-occurred in 10 patients (16.7%) in the TXA group compared with 5 patients (8.3%) in the ϵACA group (P = 0.17). There were no significant differences in the secondary end points of 30-day all-cause mortality, thromboembolic events, renal dysfunction, and seizure. CONCLUSIONS: There were no differences in the efficacy and safety outcomes between TXA and ϵACA in the management of cardiovascular surgical bleeding at our institution. Considering the substantial cost difference and comparable efficacy and safety, ϵACA may have better value over TXA for reducing cardiovascular surgical bleeding.

Validation of SeptiCyte RAPID to Discriminate Sepsis from Non-Infectious Systemic Inflammation.

(1) Background: SeptiCyte RAPID is a molecular test for discriminating sepsis from non-infectious systemic inflammation, and for estimating sepsis probabilities. The objective of this study was the clinical validation of SeptiCyte RAPID, based on testing retrospectively banked and prospectively collected patient samples. (2) Methods: The cartridge-based SeptiCyte RAPID test accepts a PAXgene blood RNA sample and provides sample-to-answer processing in ~1 h. The test output (SeptiScore, range 0-15) falls into four interpretation bands, with higher scores indicating higher probabilities of sepsis. Retrospective (N = 356) and prospective (N = 63) samples were tested from adult patients in ICU who either had the systemic inflammatory response syndrome (SIRS), or were suspected of having/diagnosed with sepsis. Patients were clinically evaluated by a panel of three expert physicians blinded to the SeptiCyte test results. Results were interpreted under either the Sepsis-2 or Sepsis-3 framework. (3) Results: Under the Sepsis-2 framework, SeptiCyte RAPID performance for the combined retrospective and prospective cohorts had Areas Under the ROC Curve (AUCs) ranging from 0.82 to 0.85, a negative predictive value of 0.91 (sensitivity 0.94) for SeptiScore Band 1 (score range 0.1-5.0; lowest risk of sepsis), and a positive predictive value of 0.81 (specificity 0.90) for SeptiScore Band 4 (score range 7.4-15; highest risk of sepsis). Performance estimates for the prospective cohort ranged from AUC 0.86-0.95. For physician-adjudicated sepsis cases that were blood culture (+) or blood, urine culture (+)(+), 43/48 (90%) of SeptiCyte scores fell in Bands 3 or 4. In multivariable analysis with up to 14 additional clinical variables, SeptiScore was the most important variable for sepsis diagnosis. A comparable performance was obtained for the majority of patients reanalyzed under the Sepsis-3 definition, although a subgroup of 16 patients was identified that was called septic under Sepsis-2 but not under Sepsis-3. (4) Conclusions: This study validates SeptiCyte RAPID for estimating sepsis probability, under both the Sepsis-2 and Sepsis-3 frameworks, for hospitalized patients on their first day of ICU admission.

Systemic steroids in severe sepsis and septic shock.

Despite more than 5 decades of study and debate, the role of corticosteroid treatment in patients with severe sepsis and septic shock remains controversial. Data support a beneficial effect on systemic blood pressure in patients with septic shock. However, the ability of corticosteroid therapy to improve mortality in patients with severe sepsis and septic shock remains controversial, with contradictory results from recent large multicenter clinical trials. Although it appears clear that high-dose corticosteroid treatment provides no benefit and possibly harm in septic patients, the experimental design flaws and biases of recent low-dose (physiologic) steroid treatment trials limit their ability to provide adequate answers to the important questions of which septic patients should be treated, how much steroid to give, and the optimum duration of treatment. Unfortunately, the answer to these important questions is not readily evident based on the current evidence or the application of metaanalysis to the available clinical data. This concise evidence-based review highlights the strengths and weaknesses of the current data to inform the practicing clinician as to which patients are likely to derive significant benefit from corticosteroid treatment, while we await more definitive guidance from future multicenter, prospective, randomized, controlled trials designed to better answer these important therapeutic questions.

Effect of Pharmacoprophylaxis on Postoperative Outcomes in Adult Elective Colorectal Surgery: A Multi-Center Retrospective Cohort Study within an Enhanced Recovery after Surgery Framework.

BACKGROUND: The application of enhanced recovery after surgery principles decreases postoperative complications (POCs), length of stay (LOS), and readmissions. Pharmacoprophylaxis decreases morbidity, but the effect of specific regimens on clinical outcomes is unclear. METHODS AND MATERIALS: Records of 476 randomly selected adult patients who underwent elective colorectal surgeries (ECRS) at 10 US hospitals were abstracted. Primary outcomes were surgical site infection (SSI), venous thromboembolism (VTE), postoperative nausea and vomiting (PONV), pain, and ileus rates. Secondary outcomes included LOS and 7- and 30-day readmission rates. RESULTS: POC rates were SSI (3.4%), VTE (1.5%), PONV (47.9%), pain (58.1%), and ileus (16.1%). Cefazolin 2 g/metronidazole 500 mg and ertapenem 1 g were associated with the shortest LOS; cefotetan 2 g and cefoxitin 2 g with the longest LOS. No SSI occurred with ertapenem and cefotetan. More Caucasians than Blacks received oral antibiotics before intravenous antibiotics without impact. Enoxaparin 40 mg subcutaneously daily was the most common inpatient and discharge VTE prophylaxis. All in-hospital VTEs occurred with unfractionated heparin. Most received rescue rather than around-the-clock antiemetics. Scopolamine patches, spinal opioids, and IV lidocaine continuous infusion were associated with lower PONV. Transversus abdominis plane block with long-acting local anesthetics, celecoxib, non-anesthetic ketamine bolus, ketorolac IV, lidocaine IV, and pregabalin were associated with lower in-hospital pain severity rates. Gabapentinoids and alvimopan were associated with lower ileus rates. Acetaminophen, alvimopan, famotidine, and lidocaine patches were associated with shorter LOS. CONCLUSIONS: Significant differences in pharmacotherapy regimens that may improve primary and secondary outcomes in ECRS were identified. In adult ECRS, cefotetan or ertapenem may be better regimens for preventing in-hospital SSI, while ertapenem or C/M may lead to shorter LOS. The value of OA to prevent SSI was not demonstrated. Inpatient enoxaparin, compared to UFH, may reduce VTE rates with a similar LOS. A minority of patients had a documented PONV risk assessment, and a majority used as-needed rather than around-the-clock strategies. Preoperative scopolamine patches continued postoperatively may lower PONV and PDNV severity and shorter LOS. Alvimopan may reduce ileus and shorten LOS. Anesthesia that includes TAP block, ketorolac IV, and pregabalin use may lead to reduced pain rates. Acetaminophen, alvimopan, famotidine, and lidocaine patches may shorten LOS. Given the challenges of pain management and the incidence of PONV/PDNV found in this study, additional studies should be conducted to determine optimal opioid-free anesthesia and the benefit of newer antiemetics on patient outcomes. Moreover, future research should identify latent pharmacotherapy variables that impact patient outcomes, correlate pertinent laboratory results, and examine the impact of order or care sets used for ECRS at study hospitals.

Pediatric Perioperative Clinical Pharmacy Practice: Clinical Considerations and Management: An Opinion of the Pediatrics and Perioperative Care Practice and Research Networks of the American College of Clinical Pharmacy.

Pediatric perioperative clinical pharmacists are uniquely positioned to provide therapeutic and medication management expertise at a particularly vulnerable transition of care from the preoperative space, through surgery, and postoperative setting. There are many direct-patient care activities that are included in the role of the pediatric perioperative pharmacist, as well as many opportunities to develop effective, optimized, and safe medication use processes. This article outlines many of the areas in which a pediatric perioperative clinical pharmacist may intervene.

Ketamine in Critically Ill Patients: Use, Perceptions, and Potential Barriers.

Objective: To evaluate practitioner use of ketamine and identify potential barriers to use in acutely and critically ill patients. To compare characteristics, beliefs, and practices of ketamine frequent users and non-users. Methods: An online survey developed by members of the Society of Critical Care Medicine (SCCM) Clinical Pharmacy and Pharmacology Section was distributed to physician, pharmacist, nurse practitioner, physician assistant and nurse members of SCCM. The online survey queried SCCM members on self-reported practices regarding ketamine use and potential barriers in acute and critically ill patients. Results: Respondents, 341 analyzed, were mostly adult physicians, practicing in the United States at academic medical centers. Clinicians were comfortable or very comfortable using ketamine to facilitate intubation (80.0%), for analgesia (77.9%), procedural sedation (79.4%), continuous ICU sedation (65.8%), dressing changes (62.4%), or for asthma exacerbation and status epilepticus (58.8% and 40.4%). Clinicians were least comfortable with ketamine use for alcohol withdrawal and opioid detoxification (24.7% and 23.2%). Most respondents reported "never" or "infrequently" using ketamine preferentially for continuous IV analgesia (55.6%) or sedation (61%). Responses were mixed across dosing ranges and duration. The most common barriers to ketamine use were adverse effects (42.6%), other practitioners not routinely using the medication (41.5%), lack of evidence (33.5%), lack of familiarity (33.1%), and hospital/institutional policy guiding the indication for use (32.3%). Conclusion: Although most critical care practitioners report feeling comfortable using ketamine, there are many inconsistencies in practice regarding dose, duration, and reasons to avoid or limit ketamine use. Further educational tools may be targeted at practitioners to improve appropriate ketamine use.

The effect of time to antifungal therapy on mortality in Candidemia associated septic shock.

The timely administration of appropriate antifungal therapy for Candida bloodstream infections (CBSI) improves clinical outcomes. However, little data exist on the effect of antifungal therapy in patients with septic shock and candidemia. We describe antifungal treatment of patients with septic shock due to CBSI and its impact on in-hospital mortality. We retrospectively reviewed medical records of hospitalized patients identified with at least one positive blood culture for Candida between January 2003 and June 2007. All septic shock patients received vasopressor therapy and had candidemia within 72 hours of refractory shock. Data collected included demographics, comorbidities, antibiotic exposure, in-hospital mortality, and intensive care-related factors. Acute Physiology and Chronic Health Evaluation II scores were calculated. Time to antifungal therapy was defined as the interval between time of collection of the first positive Candida blood culture and the time when appropriate antifungal therapy was initiated. Univariate and multivariate analyses were performed to identify variables associated with in-patient mortality. Classification and regression tree analysis was used to identify the mortality breakpoint between early and late antifungal therapy. Septic shock developed in 23% (31 of 135) patients with CBSI. In-hospital mortality was 68%. Nonalbicans Candida spp. accounted for 48% of blood isolates. Appropriate antifungal therapy was administered to 24 patients; 15 (63%) of these patients died. Classification and regression tree analysis revealed that patients who received appropriate antifungal therapy within 15 hours of collecting the first positive Candida blood culture had improved survival (P = 0.03). Early, appropriate antifungal therapy improves survival among patients with septic shock due to CBSI.

Physician agreement on the diagnosis of sepsis in the intensive care unit: estimation of concordance and analysis of underlying factors in a multicenter cohort.

BACKGROUND: Differentiating sepsis from the systemic inflammatory response syndrome (SIRS) in critical care patients is challenging, especially before serious organ damage is evident, and with variable clinical presentations of patients and variable training and experience of attending physicians. Our objective was to describe and quantify physician agreement in diagnosing SIRS or sepsis in critical care patients as a function of available clinical information, infection site, and hospital setting. METHODS: We conducted a post hoc analysis of previously collected data from a prospective, observational trial (N = 249 subjects) in intensive care units at seven US hospitals, in which physicians at different stages of patient care were asked to make diagnostic calls of either SIRS, sepsis, or indeterminate, based on varying amounts of available clinical information (clinicaltrials.gov identifier: NCT02127502). The overall percent agreement and the free-marginal, inter-observer agreement statistic kappa (κ free) were used to quantify agreement between evaluators (attending physicians, site investigators, external expert panelists). Logistic regression and machine learning techniques were used to search for significant variables that could explain heterogeneity within the indeterminate and SIRS patient subgroups. RESULTS: Free-marginal kappa decreased between the initial impression of the attending physician and (1) the initial impression of the site investigator (κ free 0.68), (2) the consensus discharge diagnosis of the site investigators (κ free 0.62), and (3) the consensus diagnosis of the external expert panel (κ free 0.58). In contrast, agreement was greatest between the consensus discharge impression of site investigators and the consensus diagnosis of the external expert panel (κ free 0.79). When stratified by infection site, κ free for agreement between initial and later diagnoses had a mean value + 0.24 (range - 0.29 to + 0.39) for respiratory infections, compared to + 0.70 (range + 0.42 to + 0.88) for abdominal + urinary + other infections. Bioinformatics analysis failed to clearly resolve the indeterminate diagnoses and also failed to explain why 60% of SIRS patients were treated with antibiotics. CONCLUSIONS: Considerable uncertainty surrounds the differential clinical diagnosis of sepsis vs. SIRS, especially before organ damage has become highly evident, and for patients presenting with respiratory clinical signs. Our findings underscore the need to provide physicians with accurate, timely diagnostic information in evaluating possible sepsis.

An evaluation of amikacin nephrotoxicity in the hematology/oncology population.

Amikacin is an aminoglycoside commonly used to provide empirical double gram-negative treatment for febrile neutropenia and other suspected infections. Strategies of extended-interval and conventional dosing have been utilized extensively in the general medical population; however, data are lacking to support a dosing strategy in the hematology/oncology population. To evaluate amikacin-associated nephrotoxicity in an adult hematology/oncology population, a prospective, randomized, open-label trial was conducted at a university-affiliated medical center. Forty patients with a diagnosis consistent with a hematologic/oncologic disorder that required treatment with an aminoglycoside were randomized to either conventional or extended-interval amikacin. The occurrence of nephrotoxicity by means of an increase in serum creatinine and evaluation of efficacy via amikacin serum concentrations with respective pathogens were assessed. The occurrence of nephrotoxicity was similar between the conventional and extended-interval groups, at 10% and 5%, respectively (P = 1.00). Six patients in the conventional group had a positive culture, compared with none in the extended-interval group (P = 0.002). The occurrence of nephrotoxicity was similar between the two dosing regimens, but the distribution of risk factors was variable between the two groups. Efficacy could not be assessed.

Recognition and treatment of hyponatremia in acutely ill hospitalized patients.

OBJECTIVE: The objective of this paper was to discuss the diagnosis, pathophysiology, and management of hyponatremia among critically ill, hospitalized patients (eg, after surgery or in the intensive care unit). METHODS: English-language literature published between 1967 and 2006 was searched using several key words (AVP receptor antagonists, hyponatremia, SIADH, conivaptan, tolvaptan, and lixivaptan) and by accessing MEDLINE and ScienceDirect. Meeting abstracts from scientific sessions (American Society of Nephrology Renal Week 2004 and the Endocrine Society's 87th Annual Meeting [2005]) were reviewed. The package insert for conivaptan hydrochloride injection was referenced from . Clinical trials included in this review were randomized and placebo controlled. RESULTS: Based on the literature we researched, hyponatremia is the most common electrolyte disorder encountered in critical care and is associated with a variety of conditions, including congestive heart failure and the syndrome of inappropriate antidiuretic hormone secretion. Because hyponatremia can arise in hypervolemic, euvolemic, and hypovolemic states, clinicians may not recognize its presence and cause. Incorrect management can lead to significant morbidity and mortality. Physicians need to recognize risk factors and symptoms and use appropriate treatment guidelines for hyponatremia. Traditionally, therapy for hyponatremia has been limited by efficacy and safety concerns. Arginine vasopressin (AVP) receptor antagonists, therapeutic agents that promote aquaresis in patients with hyponatremia by targeting V(1a) receptors in the vascular smooth muscle, V(2) receptors in the kidney, or both, are under development. A dual-receptor antagonist targeting both V(1a) and V(2) receptors is now approved for the treatment of euvolemic hyponatremia in hospitalized patients. CONCLUSIONS: Hyponatremia, an electrolyte abnormality found in critically ill patients, can be associated with significant morbidity and mortality. AVP receptor antagonists show promise as effective and tolerable treatments for patients with hyponatremia.

Choice of vasopressor in septic shock: does it matter?

Septic shock is a medical emergency that is associated with mortality rates of 40-70%. Prompt recognition and institution of effective therapy is required for optimal outcome. When the shock state persists after adequate fluid resuscitation, vasopressor therapy is required to improve and maintain adequate tissue/organ perfusion in an attempt to improve survival and prevent the development of multiple organ dysfunction and failure. Controversy surrounding the optimum choice of vasopressor strategy to utilize in the management of patients with septic shock continues. A recent randomized study of epinephrine compared to norepinephrine (plus dobutamine when indicated) leads to more questions than answers.

Antibiotic therapy for pulmonary exacerbations in adults with cystic fibrosis.

Individuals with CF are living longer but often with chronic lung infections. Effective antibiotic therapy is necessary to treat life-threatening infectious exacerbations. Knowledge of the particular requirements of antibiotic therapy for the patient with CF allows the nurse to anticipate management plans, prepare for inpatient and outpatient care, and assess response to treatment.