BackgroundEarly diagnosis of sepsis enables timely resuscitation and antibiotics and prevents subsequent morbidity and mortality. Clinical approaches relying on point-in-time analysis of vital signs or lab values are often insensitive, non-specific and late diagnostic markers of sepsis. Exploring otherwise hidden information within intervals-in-time, heart rate variability (HRV) has been documented to be both altered in the presence of sepsis, and correlated with its severity. We hypothesized that by continuously tracking individual patient HRV over time in patients as they develop sepsis, we would demonstrate reduced HRV in association with the onset of sepsis.Methodology/Principal FindingsWe monitored heart rate continuously in adult bone marrow transplant (BMT) patients (n = 21) beginning a day before their BMT and continuing until recovery or withdrawal (12±4 days). We characterized HRV continuously over time with a panel of time, frequency, complexity, and scale-invariant domain techniques. We defined baseline HRV as mean variability for the first 24 h of monitoring and studied individual and population average percentage change (from baseline) over time in diverse HRV metrics, in comparison with the time of clinical diagnosis and treatment of sepsis (defined as systemic inflammatory response syndrome along with clinically suspected infection requiring treatment). Of the 21 patients enrolled, 4 patients withdrew, leaving 17 patients who completed the study. Fourteen patients developed sepsis requiring antibiotic therapy, whereas 3 did not. On average, for 12 out of 14 infected patients, a significant (25%) reduction prior to the clinical diagnosis and treatment of sepsis was observed in standard deviation, root mean square successive difference, sample and multiscale entropy, fast Fourier transform, detrended fluctuation analysis, and wavelet variability metrics. For infected patients (n = 14), wavelet HRV demonstrated a 25% drop from baseline 35 h prior to sepsis on average. For 3 out of 3 non-infected patients, all measures, except root mean square successive difference and entropy, showed no significant reduction. Significant correlation was present amongst these HRV metrics for the entire population.Conclusions/SignificanceContinuous HRV monitoring is feasible in ambulatory patients, demonstrates significant HRV alteration in individual patients in association with, and prior to clinical diagnosis and treatment of sepsis, and merits further investigation as a means of providing early warning of sepsis.

Targeting higher blood pressure targets may increase mortality in patients who have been treated with vasopressors for more than 6 h. Lower blood pressure targets were not associated with patient-important adverse events in any subgroup, including chronically hypertensive patients.

Medication errors are common and harm hospitalized patients. The authors designed and implemented an automated system to complement an existing computerized order entry system by detecting the administration of excessive doses of medication to adult in-patients with renal insufficiency. Its impact, in combination with feedback to prescribers, was evaluated in 3 participating nursing units and compared with the remainder of a tertiary care academic medical center. The baseline rate of excessive dosing was 23.2% of administered medications requiring adjustment for renal insufficiency given to patients with renal impairment on the participating units and 23.6% in the rest of the hospital. The rate fell to 17.3% with nurse feedback and 16.8% with pharmacist feedback in the participating units (P<.05 for each, relative to baseline). The rates of excessive dosing for the same time periods were 26.1% and 24.8% in the rest of the hospital. Automated detection and routine feedback can reduce the rate of excessive administration of medication in hospitalized adults with renal insufficiency.

IntroductionCardiac troponins are sensitive and specific biomarkers of myocardial necrosis. We evaluated troponin, CK, and ECG abnormalities in patients with septic shock and compared the effect of vasopressin (VP) versus norepinephrine (NE) on troponin, CK, and ECGs.MethodsThis was a prospective substudy of a randomized trial. Adults with septic shock randomly received, blinded, a low-dose infusion of VP (0.01 to 0.03 U/min) or NE (5 to 15 μg/min) in addition to open-label vasopressors, titrated to maintain a mean blood pressure of 65 to 75 mm Hg. Troponin I/T, CK, and CK-MB were measured, and 12-lead ECGs were recorded before study drug, and 6 hours, 2 days, and 4 days after study-drug initiation. Two physician readers, blinded to patient data and drug, independently interpreted ECGs.ResultsWe enrolled 121 patients (median age, 63.9 years (interquartile range (IQR), 51.1 to 75.3), mean APACHE II 28.6 (SD 7.7)): 65 in the VP group and 56 in the NE group. At the four time points, 26%, 36%, 32%, and 21% of patients had troponin elevations, respectively. Baseline characteristics and outcomes were similar between patients with positive versus negative troponin levels. Troponin and CK levels and rates of ischemic ECG changes were similar in the VP and the NE groups. In multivariable analysis, only APACHE II was associated with 28-day mortality (OR, 1.07; 95% CI, 1.01 to 1.14; P = 0.033).ConclusionsTroponin elevation is common in adults with septic shock. We observed no significant differences in troponin, CK, and ECGs in patients treated with vasopressin and norepinephrine. Troponin elevation was not an independent predictor of mortality.Trial registrationControlled-trials.com ISRCTN94845869

BackgroundHeart failure (HF) is an increasing problem for the aging population, specifically among women. The etiology of HF influences both the selection and outcome of the treatment. There are variations between genders in morbidity and mortality in different studies, possibly reflecting etiology. The objective of this study was to examine the strength of evidence available for gender differences in the etiology of chronic heart failure.MethodsComputer-assisted searches from 1980–2009 for gender differences in the etiology of heart failure were performed (Medline, EMBASE and PubMed). From 2347 abstracts reviewed based on inclusion criteria, 35 original articles were chosen for review. Data extraction was based on observational studies (prospective/retrospective cohort or cross sectional) with a mean follow up of 3 months. There was no interrater variability between the 2 reviewers on data-extraction.ResultsVentricular systolic dysfunction being more associated with male sex, but female sex was more reported to be associated with preserved left ventricular function. Ischemic etiology and associated coronary heart disease were strongly correlated with male sex. The risk for HF was dramatically more elevated for women with systolic hypertension but the association for diabetes mellitus as the etiology of HF was somewhat equal between males and females.ConclusionsOne of the limitations in reaching conclusions about gender differences in cardiovascular disease is that many major clinical trials do not include a gender analysis nor they are powered to do so as women are under-represented in most of the HF studies. The need remains for a well designed prospective study of sufficient numbers of male and female patients with and without heart failure and analyzing etiology and risk factors based on the sex differences.

BackgroundTreatment of end stage renal disease patients with short daily hemodialysis has been associated with an improvement in blood pressure. It is unclear from these studies if anti-hypertensive management had been optimized prior to starting short daily hemodialysis. Also, the potential mechanism(s) of blood pressure improvement remain to be fully elucidated.Study Design, Setting and ParticipantsWe undertook a randomized cross-over trial in adult hypertensive patients with ESRD treated with conventional hemodialysis to determine: 1) if short-daily hemodialysis is associated with a reduction in systolic blood pressure after a 3-month blood pressure optimization period and; 2) the potential mechanism(s) of blood pressure reduction. Blood pressure was measured using Canadian Hypertension Education Program guidelines. Extracellular fluid volume (ECFV) was assessed with bioimpedance. Serum catecholamines were used to assess the sympathetic nervous system. Interleukin-6 (IL-6) and thiobarbituric acid reactive substances (T-BARS) were used as markers of inflammation and oxidative stress respectively.ResultsAfter a 3-month run-in phase in which systolic blood pressure improved, there was no significant difference in pre-dialysis systolic pressure between short-daily and conventional hemodialysis (p = 0.39). However, similar blood pressures were achieved on fewer anti-hypertensive medications with short daily hemodialysis compared to conventional hemodialysis (p = 0.01). Short daily hemodialysis, compared to conventional hemodialysis, was not associated with a difference in dry weight or ECFV (p = 0.77). Sympathetic nervous system activity as assessed by plasma epinephrine (p = 1.0) and norepinephrine (p = 0.52) was also not different. Markers of inflammation (p = 0.42) and oxidative stress (p = 0.83) were also similar between the two treatment arms.ConclusionsPatients treated with short daily, compared to conventional hemodialysis, have similar blood pressure control on fewer anti-hypertensive medications. The mechanism(s) by which short daily hemodialysis allows for decreased anti-hypertensive medication use remains unclear but effects on sodium balance and changes in peripheral vascular resistance require further study.Trial RegistrationClinicalTrials.gov NCT00759967

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