Michelle Storms

Vasopressin versus Norepinephrine Infusion in Patients with Septic Shock

BACKGROUND Vasopressin is commonly used as an adjunct to catecholamines to support blood pressure in refractory septic shock, but its effect on mortality is unknown. We hypothesized that low-dose vasopressin as compared with norepinephrine would decrease mortality among patients with septic shock who were being treated with conventional (catecholamine) vasopressors. METHODS In this multicenter, randomized, double-blind trial, we assigned patients who had septic shock and were receiving a minimum of 5 microg of norepinephrine per minute to receive either low-dose vasopressin (0.01 to 0.03 U per minute) or norepinephrine (5 to 15 microg per minute) in addition to open-label vasopressors. All vasopressor infusions were titrated and tapered according to protocols to maintain a target blood pressure. The primary end point was the mortality rate 28 days after the start of infusions. RESULTS A total of 778 patients underwent randomization, were infused with the study drug (396 patients received vasopressin, and 382 norepinephrine), and were included in the analysis. There was no significant difference between the vasopressin and norepinephrine groups in the 28-day mortality rate (35.4% and 39.3%, respectively; P=0.26) or in 90-day mortality (43.9% and 49.6%, respectively; P=0.11). There were no significant differences in the overall rates of serious adverse events (10.3% and 10.5%, respectively; P=1.00). In the prospectively defined stratum of less severe septic shock, the mortality rate was lower in the vasopressin group than in the norepinephrine group at 28 days (26.5% vs. 35.7%, P=0.05); in the stratum of more severe septic shock, there was no significant difference in 28-day mortality (44.0% and 42.5%, respectively; P=0.76). A test for heterogeneity between these two study strata was not significant (P=0.10). CONCLUSIONS Low-dose vasopressin did not reduce mortality rates as compared with norepinephrine among patients with septic shock who were treated with catecholamine vasopressors. (Current Controlled Trials number, ISRCTN94845869 [controlled-trials.com].).

Interaction of vasopressin infusion, corticosteroid treatment, and mortality of septic shock

Objective:Vasopressin and corticosteroids are often added to support cardiovascular dysfunction in patients who have septic shock that is nonresponsive to fluid resuscitation and norepinephrine infusion. However, it is unknown whether vasopressin treatment interacts with corticosteroid treatment. Design:Post hoc substudy of a multicenter randomized blinded controlled trial of vasopressin vs. norepinephrine in septic shock. Setting:Twenty-seven Intensive Care Units in Canada, Australia, and the United States. Patients:Seven hundred and seventy-nine patients who had septic shock and were ongoing hypotension requiring at least 5 &mgr;g/min of norepinephrine infusion for 6 hours. Interventions:Patients were randomized to blinded vasopressin (0.01–0.03 units/min) or norepinephrine (5–15 &mgr;g/min) infusion added to open-label vasopressors. Corticosteroids were given according to clinical judgment at any time in the 28-day postrandomization period. Measurements:The primary end point was 28-day mortality. We tested for interaction between vasopressin treatment and corticosteroid treatment using logistic regression. Secondary end points were organ dysfunction, use of open-label vasopressors and vasopressin levels. Main Results:There was a statistically significant interaction between vasopressin infusion and corticosteroid treatment (p = 0.008). In patients who had septic shock and were also treated with corticosteroids, vasopressin, compared to norepinephrine, was associated with significantly decreased mortality (35.9% vs. 44.7%, respectively, p = 0.03). In contrast, in patients who did not receive corticosteroids, vasopressin was associated with increased mortality compared with norepinephrine (33.7% vs. 21.3%, respectively, p = 0.06). In patients who received vasopressin infusion, use of corticosteroids significantly increased plasma vasopressin levels by 33% at 6 hours (p = 0.006) to 67% at 24 hours (p = 0.025) compared with patients who did not receive corticosteroids. Conclusions:There is a statistically significant interaction between vasopressin and corticosteroids. The combination of low-dose vasopressin and corticosteroids was associated with decreased mortality and organ dysfunction compared with norepinephrine and corticosteroids.

Reinfection with hepatitis C virus following sustained virological response in injection drug users.

Background and Aim:  Despite that 60–90% of injection drug users (IDUs) are infected with hepatitis C virus (HCV) infection, IDUs are often denied therapy based on concerns of reinfection following treatment. However, there are little data in this regard. We evaluated HCV re‐infection following sustained virologic response (SVR) among HCV‐infected IDUs having received HCV treatment in a multidisciplinary program.

Cardiac ischemia in patients with septic shock randomized to vasopressin or norepinephrine.

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

Agreement in electrocardiogram interpretation in patients with septic shock.

Objective:The reliability of electrocardiogram interpretation to diagnose myocardial ischemia in critically ill patients is unclear. In adults with septic shock, we assessed intra- and inter-rater agreement of electrocardiogram interpretation, and the effect of knowledge of troponin values on these interpretations. Design:Prospective substudy of a randomized trial of vasopressin vs. norepinephrine in septic shock. Setting:Nine Canadian intensive care units. Patients:Adults with septic shock requiring at least 5 &mgr;g/min of norepinephrine for 6 hrs. Interventions:Twelve-lead electrocardiograms were recorded before study drug, and 6 hrs, 2 days, and 4 days after study drug initiation. Measurements:Two physician readers, blinded to patient data and group, independently interpreted electrocardiograms on three occasions (first two readings were blinded to patient data; third reading was unblinded to troponin). To calibrate and refine definitions, both readers initially reviewed 25 trial electrocardiograms representing normal to abnormal. Cohens Kappa and the &phgr; statistic were used to analyze intra- and inter-rater agreement. Results:One hundred twenty-one patients (62.2 ± 16.5 yrs, Acute Physiology and Chronic Health Evaluation II 28.6 ± 7.7) had 373 electrocardiograms. Blinded to troponin, readers 1 and 2 interpreted 46.4% and 30.0% of electrocardiograms as normal, and 15.3% and 12.3% as ischemic, respectively. Intrarater agreement was moderate for overall ischemia (&kgr; 0.54 and 0.58), moderate/good for “normal” (&kgr; 0.69 and 0.55), fair to good for specific signs of ischemia (ST elevation, T inversion, and Q waves, reader 1 &kgr; 0.40 to 0.69; reader 2 &kgr; 0.56 to 0.70); and good/very good for atrial arrhythmias (&kgr; 0.84 and 0.79) and bundle branch block (&kgr; 0.88 and 0.79). Inter-rater agreement was fair for ischemia (&kgr; 0.29), moderate for ST elevation (&kgr; 0.48), T inversion (&kgr; 0.52), and Q waves (&kgr; 0.44), good for bundle branch block (&kgr; 0.78), and very good for atrial arrhythmias (&kgr; 0.83). Inter-rater agreement for ischemia improved from fair to moderate (&kgr; 0.52, p = .028) when unblinded to troponin. Conclusions:In patients with septic shock, inter-rater agreement of electrocardiogram interpretation for myocardial ischemia was fair, and improved with troponin knowledge.

Erratum to: Cardiac ischemia in patients with septic shock randomized to vasopressin or norepinephrine

Unfortunately this article [1] published without its additional files (Additional files 1, 2, 3, 4, 5, 6 and 7). Please see these listed below and attached as additional files to this erratum.

Substitution of tenofovir for nucleoside analogues in virologically controlled HIV-infected patients co-infected with hepatitis C virus: TEN-SWITCH

Address: 1National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Darlinghurst, Australia, 2Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, Canada, 3Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada, 4Cool Aid Community Health Centre, Victoria, British Columbia, Canada, 5Department of Statistics and Actuarial Science, University of Waterloo, Waterloo, Ontario, Canada and 6Pender Community Health Centre, Vancouver Coastal Health, Vancouver, British Columbia, Canada * Corresponding author