Adverse cardiac events during catecholamine vasopressor therapy: a prospective observational study

Purpose: To determine the incidence of and risk factors for adverse cardiac events during catecholamine vasopressor therapy in surgical intensive care unit patients with cardiovascular failure. Methods: The occurrence of any of seven predefined adverse cardiac events (prolonged elevated heart rate, tachyarrhythmia, myocardial cell damage, acute cardiac arrest or death, pulmonary hypertension-induced right heart dysfunction, reduction of systemic blood flow) was prospectively recorded during catecholamine vasopressor therapy lasting at least 12h. Results: Fifty-four of 112 study patients developed a total of 114 adverse cardiac events, an incidence of 48.2% (95% CI, 38.8-57.6%). New-onset tachyarrhythmia (49.1%), prolonged elevated heart rate (23.7%), and myocardial cell damage (17.5%) occurred most frequently. Aside from chronic liver diseases, factors independently associated with the occurrence of adverse cardiac events included need for renal replacement therapy, disease severity (assessed by the Simplified Acute Physiology Score II), number of catecholamine vasopressors (OR, 1.73; 95% CI, 1.08-2.77; p=0.02) and duration of catecholamine vasopressor therapy (OR, 1.01; 95% CI, 1-1.01; p=0.002). Patients developing adverse cardiac events were on catecholamine vasopressors (p<0.001) and mechanical ventilation (p<0.001) for longer and had longer intensive care unit stays (p<0.001) and greater mortality (25.9 vs. 1.7%; p<0.001) than patients who did not. Conclusions: Adverse cardiac events occurred in 48.2% of surgical intensive care unit patients with cardiovascular failure and were related to morbidity and mortality. The extent and duration of catecholamine vasopressor therapy were independently associated with and may contribute to the pathogenesis of adverse cardiac event

Concomitant arginine-vasopressin and hydrocortisone therapy in severe septic shock: association with mortality

Purpose: To evaluate the association between concomitant arginine-vasopressin (AVP)/hydrocortisone therapy and mortality in severe septic shock patients. Methods: This retrospective study included severe septic shock patients treated with supplementary AVP. To test the association between concomitant AVP/hydrocortisone use and mortality, a multivariate regression and Cox model (adjusted for admission year, initial AVP dosage and the Sepsis-related Organ Failure Assessment score before AVP) as well as a propensity score-based analysis were used. In both models, intensive care unit (ICU) and 28-day mortality served as outcome variables. Results: One hundred fifty-nine patients were included. Hydrocortisone was administered to 76 (47.8%) at a median daily dosage of 300 (200-300)mg. In the multivariate logistic regression model, concomitant use of AVP and hydrocortisone was associated with a trend towards lower ICU (OR, 0.51; CI 95%, 0.24-1.08; p=0.08) and 28-day (HR, 0.69; CI 95%, 0.43-1.08; p=0.11) mortality. The probability of survival at day 28, as predicted by the regression model, was significantly higher in patients treated with concomitant AVP and hydrocortisone compared to those receiving AVP without hydrocortisone (p=0.001). In a propensity score-based analysis, ICU (45 vs. 65%; OR, 0.69; CI 95% 0.38-1.26; p=0.23) and 28-day mortality (35.5 vs. 55%; OR, 0.59; CI 95%, 0.27-1.29; p=0.18) was not different between patients treated with (n=40) or without concomitant hydrocortisone (n=40). Conclusion: Concomitant AVP and hydrocortisone therapy may be associated with a survival benefit in septic shock. An adequately powered, randomised controlled trial appears warranted to confirm these preliminary, hypothesis-generating result

Arterial blood pressure during early sepsis and outcome

Objective: To evaluate the association between arterial blood pressure (ABP) during the first 24h and mortality in sepsis. Design: Retrospective cohort study. Setting: Multidisciplinary intensive care unit (ICU). Patients and participants: A total of 274 septic patients. Interventions: None. Measurements and results: Hemodynamic, and laboratory parameters were extracted from a PDMS database. The hourly time integral of ABP drops below clinically relevant systolic arterial pressure (SAP), mean arterial pressure (MAP), and mean perfusion pressure (MPP=MAP−central venous pressure) levels was calculated for the first 24h after ICU admission and compared with 28-day-mortality. Binary and linear regression models (adjusted for SAPS II as a measure of disease severity), and a receiver operating characteristic (ROC) analysis were applied. The areas under the ROC curve were largest for the hourly time integrals of ABP drops below MAP60mmHg (0.779 vs. 0.764 for ABP drops below MAP55mmHg; P≤0.01) and MPP 45mmHg. No association between the hourly time integrals of ABP drops below certain SAP levels and mortality was detected. One or more episodes of MAP<60mmHg increased the risk of death by 2.96 (CI 95%, 1.06-10.36, P=0.04). The area under the ROC curve to predict the need for renal replacement therapy was highest for the hourly time integral of ABP drops below MAP75mmHg. Conclusions: A MAP level≥60mmHg may be as safe as higher MAP levels during the first 24h of ICU therapy in septic patients. A higher MAP may be required to maintain kidney functio

Comparing two different arginine vasopressin doses in advanced vasodilatory shock: a randomized, controlled, open-label trial

Purpose: To compare the effects of two arginine vasopressin (AVP) dose regimens on the hemodynamic response, catecholamine requirements, AVP plasma concentrations, organ function and adverse events in advanced vasodilatory shock. Methods: In this prospective, controlled, open-label trial, patients with vasodilatory shock due to sepsis, systemic inflammatory response syndrome or after cardiac surgery requiring norepinephrine >0.6μg/kg/min were randomized to receive a supplementary AVP infusion either at 0.033IU/min (n=25) or 0.067IU/min (n=25). The hemodynamic response, catecholamine doses, laboratory and organ function variables as well as adverse events (decrease in cardiac index or platelet count, increase in liver enzymes or bilirubin) were recorded before, 1, 12, 24 and 48h after randomization. A linear mixed effects model was used for statistical analysis in order to account for drop-outs during the observation period. Results: Heart rate and norepinephrine requirements decreased while MAP increased in both groups. Patients receiving AVP at 0.067IU/min required less norepinephrine (P=0.006) than those infused with AVP at 0.033IU/min. Arterial lactate and base deficit decreased while arterial pH increased in both groups. During the observation period, AVP plasma levels increased in both groups (both P<0.001), but were higher in the 0.067IU/min group (P<0.001) and in patients on concomitant hydrocortisone. The rate of adverse events and intensive care unit mortality was comparable between groups (0.033IU/min, 52%; 0.067IU/min, 52%; P=1). Conclusions: A supplementary AVP infusion of 0.067IU/min restores cardiovascular function in patients with advanced vasodilatory shock more effectively than AVP at 0.033IU/mi

Antifactor Xa activity in critically ill patients receiving antithrombotic prophylaxis with standard dosages of certoparin: a prospective, clinical study

INTRODUCTION: Deep venous thrombosis with subsequent pulmonary embolism or post-thrombotic syndrome is a feared complication in the intensive care unit. Therefore, routine prophylactic anticoagulation is widely recommended. Aside from unfractionated heparin, low molecular weight heparins, such as certoparin, have become increasingly used for prophylactic anticoagulation in critically ill patients. In this prospective study, we evaluated the potency of 3,000 IU certoparin administered once daily to reach antithrombotic antifactor Xa (aFXa) levels of 0.1 to 0.3 IU/ml in 62 critically ill patients. METHODS: AFXa levels were determined 4, 12 and 24 h after injection of certoparin. Prothrombin time, activated partial thromboplastin time, antithrombin, fibrinogen, hemoglobin, platelet count, serum urea and creatinine concentrations were documented before and 12 and 24 h after injection of certoparin. RESULTS: Four hours after certoparin injection (n = 32), 28% of patients were within the antithrombotic aFXa range. After 12 and 24 h, 6% achieved antithrombotic aFXa levels. Because of a severe pulmonary embolism in one study patient, an interim analysis was performed, and the dosage of certoparin was increased to 3,000 IU twice daily. This regime attained recommended antithrombotic aFXa levels in 47%, 27%, 40% and 30% of patients at 4, 12, 16 and 24 h, respectively, after twice daily certoparin injection (n = 30). Antithrombin and fibrinogen concentrations slightly increased during the observation period. Low antithrombin concentrations before certoparin were independently correlated with underdosing of certoparin. Patients with aFXa levels <0.1 IU/ml 4 h after certoparin injection required vasopressors more often and had lower serum concentrations of creatinine and urea than patients with antithrombotic aFXa levels. CONCLUSION: Standard dosages of certoparin of 3,000 IU given once or twice daily are ineffective for attaining the recommended aFXa levels of 0.1 to 0.3 IU/ml in critically ill patients. Low antithrombin levels before certoparin administration were independently associated with low aFXa levels. Renal function and vasopressor therapy may further influence the effectiveness of certoparin in ensuring adequate antithrombotic prophylaxis

Arterial blood pressure during early sepsis and outcome

OBJECTIVE: To evaluate the association between arterial blood pressure (ABP) during the first 24 h and mortality in sepsis. DESIGN: Retrospective cohort study. SETTING: Multidisciplinary intensive care unit (ICU). PATIENTS AND PARTICIPANTS: A total of 274 septic patients. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Hemodynamic, and laboratory parameters were extracted from a PDMS database. The hourly time integral of ABP drops below clinically relevant systolic arterial pressure (SAP), mean arterial pressure (MAP), and mean perfusion pressure (MPP = MAP - central venous pressure) levels was calculated for the first 24 h after ICU admission and compared with 28-day-mortality. Binary and linear regression models (adjusted for SAPS II as a measure of disease severity), and a receiver operating characteristic (ROC) analysis were applied. The areas under the ROC curve were largest for the hourly time integrals of ABP drops below MAP 60 mmHg (0.779 vs. 0.764 for ABP drops below MAP 55 mmHg; P or = 60 mmHg may be as safe as higher MAP levels during the first 24 h of ICU therapy in septic patients. A higher MAP may be required to maintain kidney function