Andreas J. Mayr

Arginine Vasopressin in Advanced Vasodilatory Shock. A Prospective, Randomized, Controlled Study

Background—Vasodilatory shock is a potentially lethal complication of severe disease in critically ill patients. Currently, catecholamines are the most widely used vasopressor agents to support blood pressure, but loss of catecholamine pressor effects is a well-known clinical dilemma. Arginine vasopressin (AVP) has recently been shown to be a potent vasopressor agent to stabilize cardiocirculatory function even in patients with catecholamine-resistant vasodilatory shock. Methods and Results—Forty-eight patients with catecholamine-resistant vasodilatory shock were prospectively randomized to receive a combined infusion of AVP and norepinephrine (NE) or NE infusion alone. In AVP patients, AVP was infused at a constant rate of 4 U/h. Hemodynamic, acid/base, single-organ, and tonometrically derived gastric variables were reported before the study and 1, 12, 24, and 48 hours after study entry. For statistical analysis, a mixed-effects model was used. AVP patients had significantly lower heart rate, NE requirements, and incidence of new-onset tachyarrhythmias than NE patients. Mean arterial pressure, cardiac index, stroke volume index, and left ventricular stroke work index were significantly higher in AVP patients. NE patients developed significantly more new-onset tachyarrhythmias than AVP patients (54.3% versus 8.3%). Gastrointestinal perfusion as assessed by gastric tonometry was better preserved in AVP-treated patients. Total bilirubin concentrations were significantly higher in AVP patients. Conclusions—The combined infusion of AVP and NE proved to be superior to infusion of NE alone in the treatment of cardiocirculatory failure in catecholamine-resistant vasodilatory shock.

The effects of vasopressin on systemic hemodynamics in catecholamine-resistant septic and postcardiotomy shock: A retrospective analysis

We retrospectively investigated the effects of continuous arginine vasopressin (AVP) infusion on systemic hemodynamics, acid/base status, and laboratory variables in patients (mean age [mean ± sd]= 66.3 ± 10.1 yr) with catecholamine-resistant septic (n = 35) or postcardiotomy shock (n = 25). Hemodynamic and acid/base data were obtained before; 30 min after; and 1, 4, 12, 24, 48, and 72 h after the start of AVP infusion. Laboratory examinations were recorded before and 24, 48, and 72 h after the start of AVP infusion. For statistical analysis, a mixed-effects model was used. The overall intensive care unit mortality was 66.7%. AVP administration caused a significant increase in mean arterial pressure (+29%) and systemic vascular resistance (+56%), accompanied by a significant decrease in heart rate (−24%) and mean pulmonary arterial pressure (−11%) without any change in stroke volume index. Norepinephrine requirements could be reduced by 72% within 72 h. During AVP infusion, a significant increase in liver enzymes and total bilirubin concentration and a significant decrease in platelet count occurred. Arginine vasopressin was effective in reversing systemic hypotension. However, adverse effects on gastrointestinal perfusion and coagulation cannot be excluded.

Ischemic skin lesions as a complication of continuous vasopressin infusion in catecholamine-resistant vasodilatory shock: incidence and risk factors.

ObjectiveTo report on the incidence and risk factors associated with the development of ischemic skin lesions (ISL) in critically ill patients with catecholamine-resistant vasodilatory shock treated with a continuous infusion of arginine-vasopressin (AVP). DesignRetrospective analysis. SettingTwelve-bed general and surgical intensive care unit in a university hospital. PatientsA total of 63 critically ill patients with catecholamine-resistant vasodilatory shock. InterventionsContinuous AVP infusion. Measurements and Main ResultsDemographic, hemodynamic, laboratory data, and skin status were evaluated 24 hrs before and during AVP therapy (24 and 48 hrs). Patients were grouped according to development of new ISL during AVP therapy. A mixed-effects model was used to compare groups. A multiple logistic regression analysis was used to identify independent risk factors for the development of ISL. ISL developed in 19 of 63 patients (30.2%). Thirteen of 19 patients (68%) developed ISL in distal limbs, two patients (10.5%) developed ISL of the trunk, four patients (21%) developed ISL in distal limbs and in the trunk. Five patients (26%) had additional ischemia of the tongue. Body mass index, preexistent peripheral arterial occlusive disease, presence of septic shock, and norepinephrine requirements were significantly higher in patients developing ISL. ISL patients received significantly more units of fresh frozen plasma and thrombocyte concentrates than patients without ISL. Preexistent peripheral arterial occlusive disease and presence of septic shock were independently associated with the development of ISL during AVP therapy. ConclusionsISLs are a common complication during continuous AVP infusion in patients with catecholamine-resistant vasodilatory shock. The presence of septic shock and a history of peripheral arterial occlusive disease are independent risk factors for the development of ISL.

Blunted erythropoietic response to anemia in multiply traumatized patients.

ObjectivesTo assess the relations between anemia, serum erythropoietin (EPO), iron status, and inflammatory mediators in multiply traumatized patients. DesignProspective observational study. SettingIntensive care unit. PatientsTwenty-three patients suffering from severe trauma (injury severity score ≥30). InterventionsNone. Measurements and Main Results Blood samples were collected within 12 hrs after the accident (day 1) and in the morning on days 2, 4, 6, and 9 to determine blood cell status, serum EPO, tumor necrosis factor-&agr; (TNF-&agr;), soluble tumor necrosis factor-receptor I (sTNF-rI), interleukin-1 receptor antagonist (IL1-ra), interleukin-6 (IL-6), neopterin, and iron status, respectively. Hemoglobin concentration was low at admission (mean, 10.0 g/dL; range, 6.8–12.9 g/dL) and did not increase during the observation time. Serum EPO concentration was 49.8 U/L (mean value) on day 1 and did not show significant increases thereafter. No correlation was found between EPO and hemoglobin concentrations. TNF-&agr; remained within the normal range. sTNF-rI was high at admission and increased further. IL1-ra was above the normal range. IL-6 was very high at admission and did not decrease thereafter. The initial neopterin concentration was normal, but increased until day 9. Serum iron was significantly decreased on day 2 posttrauma and remained low during the study. Serum ferritin increased steadily from day 2, reaching its maximum on day 9. In contrast, concentrations of transferrin were low from admission onward. ConclusionsMultiply traumatized patients exhibit an inadequate EPO response to low hemoglobin concentrations. Thus, anemia in severe trauma is the result of a complex network of bleeding, blunted EPO response to low hemoglobin concentrations, inflammatory mediators, and a hypoferremic state.

Tachyarrhythmias in a surgical intensive care unit: a case-controlled epidemiologic study.

Objective: Incidence, types, and factors associated with new onset tachyarrhythmias (TA) in surgical intensive care patients.¶Design: Pairwise-matched case-controlled study. Setting: Surgical intensive care unit (ICU) with nine intensive care beds. Patients: During a 1-year period, all TA patients (n = 89) were included in the study. Control patients (n = 82) without TA were matched according to age, sex, and surgical region. Methods: TA workup included: 12-lead ECG, arterial blood gas, serum electrolyte (K+, Mg2+), and serum CK/CKMB isoenzyme analysis. Pre-existing cardiovascular and pulmonary disease, cardiovascular risk factors, preoperative regular medication, and admission SAPS were recorded in all patients. A multiple organ dysfunction syndrome (MODS) score, the presence or absence of SIRS or sepsis, and hemodynamics (MAP and CVP) before onset of TA were evaluated in TA patients, while in control patients highest MODSscore, the presence or absence of SIRS or sepsis, mean hemodynamic and laboratory values calculated from highest and lowest readings during ICU stay were used for statistical comparison. Logistic regression analysis was performed to identify variables multivariately associated with TA. Results: Eighty-nine (14.8 %) of 596 patients developed TA. Atrial fibrillation was most frequent (60.7 %). Presence of SIRS or sepsis (adj. OR = 36.45; 95 % CI: 11.5–115.5), high admission SAPS (adj. OR = 1.25/point; 95 % CI: 1.08–1.44), high CVP (adj. OR = 1.27/mmHg; 95 % CI: 1.09–1.48), and low arterial oxygen tension (adj. OR = 0.97/mmHg); 95 % CI: 0.95–0.99) were found to be significant predictors for development of TA. Conclusions: In surgical patients hypoxia, high cardiac filling pressures, a greater degree of physiologic derangement at admission, and the presence of SIRS and sepsis are independent risk factors for the development of TA.

Management of Vasodilatory Shock Defining the Role of Arginine Vasopressin

The rationale for an arginine vasopressin (argipressin) infusion was put forward after it was discovered that patients in shock states might have an endogenous arginine vasopressin deficiency. Subsequently, several investigations impressively demonstrated that arginine vasopressin can successfully stabilise haemodynamics even in advanced vasodilatory shock. We report on physiological and pharmacological aspects of arginine vasopressin, and summarise current clinical knowledge on employing a continuous arginine vasopressin infusion in critically ill patients with catecholamine-resistant vasodilatory shock of different aetiologies. In view of presented experimental evidence and current clinical experience, a continuous arginine vasopressin infusion of ∼2 to ∼6 IU/h can be considered as a supplemental strategy to vasopressor catecholamines in order to preserve cardiocirculatory homeostasis in patients with advanced vasodilatory shock. Because data on adverse effects are still limited, arginine vasopressin should be reserved for patients in whom adequate haemodynamic stabilisation cannot be achieved with conventional vasopressor therapy or who have obvious adverse effects of catecholamines that result in further significant haemodynamic deterioration. For the same reasons, arginine vasopressin should not be used as a single, alternative vasopressor agent instead of catecholamine vasopressors. Future prospective studies will be necessary to define the exact role of arginine vasopressin in the therapy of vasodilatory shock.

Antifactor Xa activity in intensive care patients receiving thromboembolic prophylaxis with standard doses of enoxaparin

BACKGROUND Low-molecular-weight heparins (LMWHs) have become increasingly used to prevent thromboembolic complications in intensive care patients. Unlike in medical and surgical patients, no data on the anticoagulant effectiveness of standard LMWH dosages exist in intensive care patients. Therefore, we prospectively investigated antifactor Xa (aFXa) levels after subcutaneous administration of 40 mg of enoxaparin in 89 intensive care patients over a 24-h period. METHODS AFXa levels were measured before, 4, 12 and 24 h after subcutaneous administration of enoxaparin. Laboratory parameters including prothrombin time, activated partial thromboplastin time, antithrombin III, fibrinogen as well as platelet count were collected at same intervals. Demographics included age, sex, height, weight, body mass index, admission diagnosis, a thromboembolic risk score and a modified Goris multiple organ dysfunction score. RESULTS At 4, 12 and 24 h, 56.5%, 39.3% and 12.6% of the study patients were within recommended antithrombotic aFXa levels (0.1-0.3 U ml(-1)). Presence of multiple organ dysfunction as well as high body weight were significantly correlated with low aFXa levels. CONCLUSION European standard dosages of 40 mg of enoxaparin once daily proved to be ineffective in achieving recommended antithrombotic aFXa levels in intensive care patients. This was most pronounced in patients with high body weight and presence of multiple organ dysfunction.

Serum vasopressin concentrations in critically ill patients.

Objective:To measure arginine vasopressin (AVP) serum concentrations in critically ill patients. Design:Prospective study. Setting:Twelve-bed general and surgical intensive care unit in a tertiary, university teaching hospital. Patients:Two-hundred-thirty-nine mixed critically ill patients and 70 healthy volunteers. Interventions:None. Measurements and Main Results:Demographic data, hemodynamic variables, vasopressor drug requirements, blood gases, AVP serum concentrations within 24 hrs after admission, multiple organ dysfunction score, and outcome were recorded. Twenty-four hours after admission, study patients had significantly higher AVP concentrations (11.9 ± 20.6 pg/mL) than healthy controls (0.92 ± 0.38 pg/mL; p < .001). Males had lower AVP concentrations than females (9.7 ± 19.5 vs. 15.1 ± 20.6 pg/mL; p = .014). Patients with hemodynamic dysfunction had higher AVP concentrations than patients without hemodynamic dysfunction (14.1 ± 27.1 vs. 8.7 ± 10.8 pg/mL; p = .042). Patients after cardiac surgery (n = 96) had significantly higher AVP concentrations when compared to patients admitted for other diagnoses (n = 143; p < .001). AVP concentrations were inversely correlated with length of stay in the intensive care unit (correlation coefficient, −0.222; p = .002). There was no correlation between serum AVP concentrations and the incidence of shock or specific hemodynamic parameters. Four (1.7%) of the 239 study patients met criteria for an absolute AVP deficiency (AVP, <0.83 pg/mL), and 32 (13.4%) met criteria for a relative AVP deficiency (AVP, <10 pg/mL, and mean arterial pressure, <70 mm Hg). In shock patients, relative AVP deficiency occurred in 22.2% (septic shock), 15.4% (postcardiotomy shock), and 10% (shock due to a severe systemic inflammatory response syndrome) (p = .316). Conclusions:AVP serum concentrations 24 hrs after intensive care unit admission were significantly increased in this mixed critically ill patient population. The lack of a correlation between AVP serum concentrations and hemodynamic parameters suggests complex dysfunction of the vasopressinergic system in critical illness. Relative and absolute AVP deficiency may be infrequent entities during acute surgical critical illness, mostly remaining without significant effects on cardiovascular function.

Effectiveness of direct-current cardioversion for treatment of supraventricular tachyarrhythmias, in particular atrial fibrillation, in surgical intensive care patients.

ObjectiveTo evaluate primary success rate and effectiveness of direct-current cardioversion in postoperative critically ill patients with new-onset supraventricular tachyarrhythmias. DesignProspective intervention study. SettingTwelve-bed surgical intensive care unit in a university teaching hospital. PatientsThirty-seven consecutive, adult surgical intensive care unit patients with new-onset supraventricular tachyarrhythmias without previous history of tachyarrhythmias. InterventionsDirect-current cardioversion using a monophasic, damped sinus-wave defibrillator. Energy levels used were 50, 100, 200, and 300 J for regular supraventricular tachyarrhythmias (n = 6) and 100, 200, and 360 J for irregular supraventricular tachyarrhythmias (n = 31). Measurements and Main ResultsNone of the patients was hypoxic, hypokalemic, or hypomagnesemic at onset of supraventricular tachyarrhythmia. Direct-current cardioversion restored sinus rhythm in 13 of 37 patients (35% primary responders). Most patients responded to the first or second direct-current cardioversion shock. Only one of 25 patients requiring more than two direct-current cardioversion shocks converted into sinus rhythm. Primary responders were significantly younger and demonstrated significant differences in arterial Po2 values at onset of supraventricular tachyarrhythmias compared with nonresponders. At 24 and 48 hrs, only six (16%) and five (13.5%) patients remained in sinus rhythm, respectively. ConclusionsIn contrast to recent literature, direct-current cardioversion proved to be an ineffective method for treatment of new-onset supraventricular tachyarrhythmias and, in particular, atrial fibrillation with a rapid ventricular response in surgical intensive care unit patients.

Risk factors associated with new onset tachyarrhythmias after cardiac surgery – a retrospective analysis

Background: Tachyarrhythmias (TA) represent a frequent and serious problem after cardiac surgery. We retrospectively analyzed 987 cardiac surgery patients admitted to a surgical intensive care unit between 1996 and 1999 to assess incidence and risk factors associated with development of postoperative TA in the intensive care unit.