Zur Wirkung von Vasopressin beim unkontrollierten hämorrhagischen Schock

Vasopressor Agents or Fluid Resuscitation for the Treatment of Uncontrolled Hemorrhagic Shock, an Experimental Approach in a Porcine Liver Trauma Model The standard approach to the traumatized victim in uncontrolled hemorrhagic shock is to infuse large amounts of crystalloid and colloid fluids as early, and as rapidly as possible. The aim of this strategy is to restore intravascular volume immediately and to maintain vital organ perfusion. The results of many laboratory studies and one clinical trial question the effectiveness of this treatment recommendation and suggest that in the case of uncontrolled hemorrhage aggressive fluid resuscitation may even be harmful. Hence, we evaluated the effects of fluid resuscitation vs. epinephrine vs. vasopressin vs. saline placebo on hemodynamic variables, regional organ blood flow, and short term survival in an animal model of uncontrolled hemorrhagic shock. Twenty-eight anesthetized pigs were subjected to a severe liver injury, which resulted in an average blood loss of 35 mL/kg within 30 minutes. When mean arterial pressure was < 20 mmHg, and heart rate declined progressively, the pigs were randomly assigned to receive either 1000 mL lactated Ringer´s solution and 1000 mL of gelatine solution (n=7), or an intravenous bolus dose and continuous infusion of 45 µg/kg epinephrine (n=7), or 0.4 IU/kg Vasopressin (n=7), or saline placebo (n=7). At 30 minutes after therapeutic intervention all surviving animals have been fluid resuscitated and further blood loss has been controlled surgically. Mean ± SEM arterial blood pressure at 5 minutes after therapeutic intervention was significantly (p< 0.0001 for vasopressin vs. epinephrine vs. placebo and p< 0.04 for vasopressin vs. fluid resuscitation) higher after vasopressin vs. fluid resuscitation vs. epinephrine vs. saline placebo (58 ± 9 vs. 32 ± 6 vs. 19 ± 5 vs. 7 ± 3 mmHg; respectively). Although vasopressin improved regional organ blood flow, this effect did not result in further blood loss stemming from the liver injury (vasopressin vs. fluid resuscitation vs. epinephrine vs. saline placebo 10 minutes after intervention, 1343 ± 60 vs. 2536 ± 93 vs. 1383 ± 117 vs. 1326 ± 46 mL; respectively; p<0.0001 for fluid resuscitation vs. all other groups). In the vasopressin group, seven of seven animals survived until bleeding was surgically controlled and lived throughout the following 60 minutes. In all the other groups all animals died within the first 20 minutes after therapeutic intervention. In conclusion, vasopressin but not fluid resuscitation, epinephrine or saline placebo improved short term survival in this porcine model of severe liver trauma and uncontrolled hemorrhagic shock.Bei der präklinischen Therapie des unkontrollierten hämorrhagischen Schocks wird eine aggressive Volumensubstitution seit Jahrzehnten als Mittel der Wahl angesehen. Ziel dieser Strategie ist v.a. die schnelle Wiederherstellung des intravaskulären Volumens. Eine Vielzahl tierexperimenteller Studien und die Ergebnisse einer klinischen Untersuchung stellen die Effektivität dieser Methode jedoch in Frage. Deshalb evaluierte man in der vorliegenden Studie vier verschiedene Therapieansätze zur Behandlung des Blutungsschocks beim Lebertrauma. Es wurde die Wirkung von aggressiver Volumensubstitution mit Adrenalin, Vasopressin und Kochsalz-Placebo-Applikation als Kontrollgruppe verglichen. Für die vorliegende Studie wurden 28 Schweine anästhesiert, beatmet und mit Kathetern zur Messung von Hämodynamik und Blutgasen instrumentiert. Nach medianer Laparotomie hat man Ultraschall-Flussmesssonden um die Leber- und Nierenarterie sowie die Pfortader gelegt, um die Organdurchblutung zu bestimmen. Im Anschluss setzte man alle Tiere in anästhesiertem Zustand einem Lebertrauma aus, welches innerhalb von 30 Minuten zu einem Blutverlust von ungefähr 35 ml/kg KG führte. Sobald der mittlere arterielle Blutdruck 20 mmHg unterschritten hatte und die Herzfrequenz abfiel, randomisierte man die Tiere und wies sie einer von vier Therapiegruppen zu. Diese erhielten entweder 2000 ml Infusionslösung (Ringer-Lactat plus Gelofusin(r)) als Druckinfusion (Gruppe-Vol, n=7), oder 45 µg/kg Adrenalin (Gruppe-Epi, n=7), 0,4 IU/kg Vasopressin (Gruppe-Vaso, n=7), oder eine Placebo- Kochsalzlösung (Gruppe-Null, n=7). Nach 30 Minuten wurde bei allen überlebenden Tieren die Blutung chirurgisch versorgt und eine Infusionstherapie mit je 1 Liter kristalloider und kolloidaler Infusionslösung begonnen. Angestrebt wurde eine anschließende Überlebensdauer von 60 Minuten. Aufgefallen ist, dass der mittlere arterielle Blutdruck in der Gruppe-Vaso bereits 5 Minuten nach Interventionsbeginn signifikant höher war, als in den Gruppen Vol, Epi oder Null (58 ± 9 vs. 32 ± 6 vs. 19 ± 5 vs. 7 ± 3 mmHg und p<0,0001 für Vaso vs. Epi und vs. Placebo sowie p<0,04 für Vaso vs. Vol). Außerdem konnte in der Gruppe-Vaso im Vergleich zur Gruppe- Vol kein weiterer Blutverlust verzeichnet werden (Vaso vs. Vol vs. Epi vs. Null, 10 min. nach Intervention, 1343 ± 60 vs. 2536 ± 93 vs. 1383 ± 117 vs. 1326 ± 46 ml, p<0,0001 für Vol vs. alle anderen Gruppen), obwohl Vasopressin die arterielle Leberdurchblutung deutlich verbesserte (p<0,01 für Vaso vs. alle anderen Gruppen). In der Gruppe-Vaso überlebten 7/7 Tiere bis zur chirurgischen Intervention und auch die 60 Minuten im Anschluss. Die Tiere aller anderen Gruppen starben bereits innerhalb der ersten 20 Minuten nach Interventionsbeginn. In der vorliegenden Studie verbesserte weder eine Flüssigkeitstherapie, noch Adrenalin oder Kochsalz-Placebo, sondern nur Vasopressin das Kurzzeitüberleben beim unkontrollierten hämorrhagischen Schock

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

Hemodynamic variables and mortality in cardiogenic shock: a retrospective cohort study

INTRODUCTION: Despite the key role of hemodynamic goals, there are few data addressing the question as to which hemodynamic variables are associated with outcome or should be targeted in cardiogenic shock patients. The aim of this study was to investigate the association between hemodynamic variables and cardiogenic shock mortality. METHODS: Medical records and the patient data management system of a multidisciplinary intensive care unit (ICU) were reviewed for patients admitted because of cardiogenic shock. In all patients, the hourly variable time integral of hemodynamic variables during the first 24 hours after ICU admission was calculated. If hemodynamic variables were associated with 28-day mortality, the hourly variable time integral of drops below clinically relevant threshold levels was computed. Regression models and receiver operator characteristic analyses were calculated. All statistical models were adjusted for age, admission year, mean catecholamine doses and the Simplified Acute Physiology Score II (excluding hemodynamic counts) in order to account for the influence of age, changes in therapies during the observation period, the severity of cardiovascular failure and the severity of the underlying disease on 28-day mortality. RESULTS: One-hundred and nineteen patients were included. Cardiac index (CI) (P = 0.01) and cardiac power index (CPI) (P = 0.03) were the only hemodynamic variables separately associated with mortality. The hourly time integral of CI drops 0.05). The hourly time integral of CPI drops 0.05). CONCLUSIONS: During the first 24 hours after intensive care unit admission, CI and CPI are the most important hemodynamic variables separately associated with 28-day mortality in patients with cardiogenic shock. A CI of 3 L/min/m2 and a CPI of 0.8 W/m2 were most predictive of 28-day mortality. Since our results must be considered hypothesis-generating, randomized controlled trials are required to evaluate whether targeting these levels as early resuscitation endpoints can improve mortality in cardiogenic shock

Association of arterial blood pressure and vasopressor load with septic shock mortality: a post hoc analysis of a multicenter trial

INTRODUCTION: It is unclear to which level mean arterial blood pressure (MAP) should be increased during septic shock in order to improve outcome. In this study we investigated the association between MAP values of 70 mmHg or higher, vasopressor load, 28-day mortality and disease-related events in septic shock. METHODS: This is a post hoc analysis of data of the control group of a multicenter trial and includes 290 septic shock patients in whom a mean MAP > or = 70 mmHg could be maintained during shock. Demographic and clinical data, MAP, vasopressor requirements during the shock period, disease-related events and 28-day mortality were documented. Logistic regression models adjusted for the geographic region of the study center, age, presence of chronic arterial hypertension, simplified acute physiology score (SAPS) II and the mean vasopressor load during the shock period was calculated to investigate the association between MAP or MAP quartiles > or = 70 mmHg and mortality or the frequency and occurrence of disease-related events. RESULTS: There was no association between MAP or MAP quartiles and mortality or the occurrence of disease-related events. These associations were not influenced by age or pre-existent arterial hypertension (all P > 0.05). The mean vasopressor load was associated with mortality (relative risk (RR), 1.83; confidence interval (CI) 95%, 1.4-2.38; P 70 mmHg by augmenting vasopressor dosages may increase mortality. Future trials are needed to identify the lowest acceptable MAP level to ensure tissue perfusion and avoid unnecessary high catecholamine infusions

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

The association between body-mass index and patient outcome in septic shock: a retrospective cohort study

Zusammenfassung: HINTERGRUND: Es bestehen keine Daten über die Assoziation zwischen dem Body Mass Index (BMI) bzw. BMI Kategorien und der Mortalität von septischen Schock-patienten. METHODEN: Die Datenbank einer interdisziplinären Intensivstation wurde retrospektiv nach erwachsenen Patienten mit septischem Schock durchsucht. Von allen Patienten wurde der BMI, demographische, klinische und laborchemische Parameter gemeinsam mit Outcomevariabeln dokumentiert. Die Studienpatienten wurden wie folgt anhand des BMI kategorisiert: BMI 30 kg/m2, Fettleibigkeit. Bivariate und multivariate logistische Regressionsmodelle wurden verwendet, um den Zusammenhang zwischen dem BMI und Outcome-variabeln zu untersuchen. RESULTATE: 301 septische Schockpatienten wurden identifiziert. Der BMI war bivariat mit der Mortalität auf der Intensivstation assoziiert (OR, 0,91; 95% CI, 0,86-0,98; p = 0,007). Es gab keine signifikante Assoziation zwischen dem BMI und der Mortalität auf der Intensivstation. Allerdings waren höhere BMI Werte trendmässig mit einer niedrigeren Intensivstations-mortalität assoziiert (OR, 0,93; 95% CI, 0,86-1,01; p = 0,09). Während übergewichtige (OR, 0,43; 95% CI, 0,19-0,98; p = 0,04) und fettleibige (OR, 0,28; 95% CI, 0,08-0,93; p = 0,04) Patienten ein unabhängig niedrigeres Risiko auf der Intensivstation zu versterben hatten als normalgewichtige Patienten, gab es keinen Unterschied im Sterberisiko zwischen normal- und untergewichtigen Patienten (p = 0,22). Ein hoher BMI war unabhängig mit einer geringen Häufigkeit eines akutem Deliriums (p = 0,04) und einer geringeren Intensivwieder-aufnahmerate (p = 0,001), aber mit mehr Harnwegsinfektionen (p = 0,02) assoziiert. SCHLUSSFOLGERUNG: Bis zu einem BMI von 50 kg/m2 scheint keine Assoziation zwischen BMI und schlechterem Überleben auf der Intensivstation oder im Krankenhaus bei septischen Schockpatienten zu bestehen. Im Gegenteil, hohe BMI Werte könnten sogar das Risiko am septischen Schock zu versterben reduziere