The course of adrenomedullin and endothelin levels in patients with vasodilatory shock after cardiac surgery compared to patients after uncomplicated elective cardiac surgery.

PURPOSE: The aim of this study was to analyse the course of adrenomedullin (ADM) and endothelin-1 (ET-1) levels in patients with vasodilatory shock after cardiac surgery and to explore differences compared to patients after uncomplicated coronary artery bypass graft (CABG) surgery. ADM and ET-1 are involved in the vasomotor response during vasodilatory shock. MATERIALS AND METHODS: We included 32 patients with vasodilatory shock (study group) and 10 patients after uncomplicated CABG surgery (control group). Daily measurements of MR-proADM and CT-proET-1 (stable surrogate markers for ADM and ET-1) were collected during the first 7 postoperative days. RESULTS: MR-proADM and CT-proET-1 levels were significantly elevated in the study group when compared to the control group. In addition, the course of both biomarkers was significantly different in the study versus control group. Higher levels of both biomarkers were associated with organ dysfunction (higher maximum multiple organ dysfunction score, acute kidney injury). CONCLUSIONS: Significantly higher levels of MR-proADM and CT-proET-1 and a different course of both biomarkers were observed in patients with vasodilatory shock after cardiac surgery and seemed to be associated with organ dysfunction.

Cell-free expression of RNA encoded genes using MS2 replicase.

RNA replicases catalyse transcription and replication of viral RNA genomes. Of particular interest for in vitro studies are phage replicases due to their small number of host factors required for activity and their ability to initiate replication in the absence of any primers. However, the requirements for template recognition by most phage replicases are still only poorly understood. Here, we show that the active replicase of the archetypical RNA phage MS2 can be produced in a recombinant cell-free expression system. We find that the 3' terminal fusion of antisense RNAs with a domain derived from the reverse complement of the wild type MS2 genome generates efficient templates for transcription by the MS2 replicase. The new system enables DNA-independent gene expression both in batch reactions and in microcompartments. Finally, we demonstrate that MS2-based RNA-dependent transcription-translation reactions can be used to control DNA-dependent gene expression by encoding a viral DNA-dependent RNA polymerase on a MS2 RNA template. Our study sheds light on the template requirements of the MS2 replicase and paves the way for new in vitro applications including the design of genetic circuits combining both DNA- and RNA-encoded systems.

Compartmentalised RNA catalysis in membrane-free coacervate protocells.

Phase separation of mixtures of oppositely charged polymers provides a simple and direct route to compartmentalisation via complex coacervation, which may have been important for driving primitive reactions as part of the RNA world hypothesis. However, to date, RNA catalysis has not been reconciled with coacervation. Here we demonstrate that RNA catalysis is viable within coacervate microdroplets and further show that these membrane-free droplets can selectively retain longer length RNAs while permitting transfer of lower molecular weight oligonucleotides.

Autologous fibroblast transplantation at the vesico-ureteral junction as potential reconstructive cell replacement in an animal model.

PURPOSE: To evaluate the cellular survival of donor fibroblasts after transplantation at the vesico-ureteral junction (VUJ) and to analyse their potential for reconstructive cell replacement in an animal model as autologous fibroblasts have been used as soft tissue augmentation material for scared and damaged tissue. METHODS: Muscles biopsies were procured from the lower limb muscles of 4 pigs; cytoplasm of fibroblasts was labelled with nano-sized iron oxide particles. Six weeks after taking of the muscle biopsies, fibroblast transplantation was performed, 3 × 10(6) cells suspended in transplantation medium (in 1-ml syringes) were injected at the VUJ using the modified STING technique. Animals were killed 8 weeks later; seeded fibroblasts were identified using prussian blue staining protocol; histological evaluation and morphological analysis were performed by light microscopy (Mayer's haematoxylin-eosin staining); and bladders were scanned by MRI for visualization and localization of the iron-labelled donor cells. RESULTS: Donor fibroblast cell colonization and cellular viability at the VUJ was demonstrated by MRI and histochemically indicating cellular uptake of iron particles at the VUJ. It was also evident that transplanted fibroblasts integrate into the extracellular matrix of the distal ureter augmenting ureteral host tissue. CONCLUSIONS: Labelled implanted autologous fibroblasts were visualized by staining procedure as well as MRI scan demonstrating persistence at the VUJ, suggesting that in vitro expanded fibroblasts survived in vivo after transplantation.

A survey of the status of education and research in anaesthesia and intensive care medicine at the University Teaching Hospital in Lusaka, Zambia.

BACKGROUND: Current knowledge of the situation of anaesthesia in developing countries is limited. A survey of the status of education and research based on hospital records, records of the anaesthesia section, nursing records, personal observations as well as personal communication with staff, patients and hospital managers was carried out in a 1863-bed university teaching hospital located in the capital of a least developed Sub-Saharan African Country. METHODS: Classification and evaluation of the data was based on the three aspects of the role of university teaching hospitals in Western countries: (I) patient care, (II) university teaching and post-graduation training, as well as (III) research activities. The section "patient care" was sub-divided into anaesthesia, intensive care medicine, emergency medicine, and pain therapy. The Department of Anaesthesia at the University Teaching Hospital of Lusaka, Zambia, is organized as a subdivision of the surgical department and is not involved in emergency medicine or pain therapy. Thirteen out of seventeen operating theatres, one recovery room, and a ten bed intensive care unit are serviced by the Department of Anaesthesia. RESULTS: Anaesthetic equipment, medical supplies, drugs, and consumables are all in limited supply. There are limited statistics on perioperative complications and mortality. Anaesthesia at the university teaching hospital of a least developed Sub-Saharan African Country is severely short of both a workforce and resources. CONCLUSION: We have described strategies which may help to reverse this trend, the most important of which is to promote anaesthesia as an essential specialty within hospitals in developing countries.

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 >0.6 microg/kg/min were randomized to receive a supplementary AVP infusion either at 0.033 IU/min (n = 25) or 0.067 IU/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 48 h 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 0.067 IU/min required less norepinephrine (P = 0.006) than those infused with AVP at 0.033 IU/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 0.067 IU/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 (0.033 IU/min, 52%; 0.067 IU/min, 52%; P = 1). CONCLUSIONS: A supplementary AVP infusion of 0.067 IU/min restores cardiovascular function in patients with advanced vasodilatory shock more effectively than AVP at 0.033 IU/min.

A prediction model for out-of-hospital cardiopulmonary resuscitation.

BACKGROUND: We created a prediction model to be used in cardiopulmonary resuscitation (CPR) attempts as a decision tool to omit futile CPR attempts and to save resources. METHODS: In this post hoc analysis, we assessed predictive parameters for neurological recovery after successful CPR. The original study was designed as a blinded, randomized, prospective, controlled, multicenter clinical trial. RESULTS: We identified 1166 prehospital cardiac arrest patients being treated with advanced cardiac life support. Seven hundred eighty-six of 1166 patients (67.4%) died at the scene and 380 of 1166 (32.6%) were brought to the hospital. Two hundred sixty-five of 1166 patients (22.7%) died in the hospital. One hundred fifteen of 1166 (9.8%) were discharged from the hospital and 92 of the 115 patients (80%) could be followed-up. Good cerebral performance was regained by 54% of discharged patients (50 of 92 patients). In 46% of patients (42/92), unconsciousness or severe disability remained. Ventricular fibrillation was more likely to have occurred in patients with good neurological recovery (42/50 = 84.0%), whereas asystole was more likely in patients with poor neurological recovery (9/42 = 21.4%). A score was developed to predict the probability of death using logistic regression analysis. Predicting death in the hospital revealed a sensitivity of 99.8% (953/955), but only a specificity of 2.9% (3/104; threshold 0.5). Predicting survival until discharge from the hospital revealed a sensitivity of 99% (103/104), but only a specificity of 8% (72/955; threshold 0.99). A receiver operating characteristic curve yielded an area under the curve of 0.795 (0.751-0.839) at a confidence interval of 95%. CONCLUSION: For out-of-hospital patients with cardiac arrest, parameters documented in the field did not allow accurate prediction of hospital survival.

Macroscopic postmortem findings in 235 surgical intensive care patients with sepsis.

BACKGROUND: Although detailed analyses of the postmortem findings of various critically ill patient groups have been published, no such study has been performed in patients with sepsis. In this retrospective cohort study, we reviewed macroscopic postmortem examinations of surgical intensive care unit (ICU) patients who died from sepsis or septic shock. METHODS: Between 1997 and 2006, the ICU database and autopsy register were reviewed for patients who were admitted to the ICU because of sepsis/septic shock, or who developed sepsis/septic shock at a later stage during their ICU stay and subsequently died from of sepsis/septic shock. Clinical data and postmortem findings were documented in all patients. RESULTS: Postmortem results of 235 patients (84.8%) were available for statistical analysis. The main causes of death as reported in the patient history were refractory multiple organ dysfunction syndrome (51.5%) and uncontrollable cardiovascular failure (35.3%). Pathologies were detected in the lungs (89.8%), kidneys/urinary tract (60%), gastrointestinal tract (54%), cardiovascular system (53.6%), liver (47.7%), spleen (33.2%), central nervous system (18.7%), and pancreas (8.5%). In 180 patients (76.6%), the autopsy revealed a continuous septic focus. The most common continuous foci were pneumonia (41.3%), tracheobronchitis (28.9%), peritonitis (23.4%), uterine/ovarial necrosis (9.8% of female patients), intraabdominal abscesses (9.1%), and pyelonephritis (6%). A continuous septic focus was observed in 63 of the 71 patients (88.7%) who were admitted to the ICU because of sepsis/septic shock and treated for longer than 7 days. CONCLUSIONS: Relevant postmortem findings explaining death in surgical ICU patients who died because of sepsis/septic shock were a continuous septic focus in approximately 80% and cardiac pathologies in 50%. The most frequently affected organs were the lungs, abdomen, and urogenital tract. More diagnostic, therapeutic and scientific efforts should be launched to identify and control the infectious focus in patients with sepsis and septic shock.

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 = 0.01) and MPP 45 mmHg. No association between the hourly time integrals of ABP drops below certain SAP levels and mortality was detected. One or more episodes of MAP < 60 mmHg 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 MAP 75 mmHg. CONCLUSIONS: A MAP level > 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.

The vasopressin and copeptin response to infection, severe sepsis, and septic shock.

OBJECTIVE: To compare the course of arginine vasopressin (AVP) and copeptin plasma concentrations between patients with infection, severe sepsis, and septic shock. DESIGN: Prospective, closed-cohort study. SETTING: Twelve-bed general and surgical intensive care unit and 33-bed internal medicine ward in a university hospital. PATIENTS: Ten patients with infection, 22 with severe sepsis, and 28 with septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Hemodynamic, laboratory and clinical data were recorded daily during the first 7 days after intensive care unit or hospital admission. Parallel thereto, blood was withdrawn to determine plasma AVP (radioimmunoassay) and copeptin (immunoluminometric assay) concentrations. Standard tests, a mixed effects model, and a linear regression analysis were used for statistical analysis. The AVP response was different between the three study groups (p < 0.001) but did not change over time (p = 0.12). Although patients with severe sepsis and septic shock had higher AVP levels than did patients with infection (both p < 0.001), no difference in AVP concentrations was seen between severe sepsis and septic shock patients (p = 0.98). No difference in AVP was observed between survivors and nonsurvivors at day 28 (p = 0.87). In patients with severe sepsis, serum osmolarity (p < 0.001), arterial pH (p = 0.001), lactate (p < 0.001), and Pao2 (p = 0.04) were associated with the course of AVP plasma levels, whereas it was serum osmolarity alone in patients with septic shock (p = 0.03). Plasma AVP concentrations correlated with copeptin (r = .614, p < 0.001), but this correlation was influenced by continuous veno-venous hemofiltration (p = 0.002). CONCLUSIONS: Severe sepsis induced a stronger AVP response than infection without systemic inflammation. However, the lack of a difference in AVP plasma concentrations between patients with and without shock indicates that the AVP system does not function normally in severe sepsis. Our data support the hypothesis that impaired AVP response is at least partially responsible for the failure to restore vascular tone in septic shock.

Postoperative vasopressin and copeptin levels in noncardiac surgery patients: a prospective controlled trial.

Further information on the endogenous arginine vasopressin (AVP) response in patients with postoperative systemic inflammatory response syndrome (SIRS) and vasodilatory shock would provide more insight into the pathophysiology of SIRS-associated cardiovascular failure and help indicate AVP therapy. Patients after uncomplicated abdominal surgery without SIRS (n = 10), critically ill patients after noncardiac surgery with SIRS (n = 9), and patients with SIRS plus vasodilatory shock (n = 22) were included in this prospective trial. Plasma AVP (radioimmunoassay) and copeptin (immunoluminometric assay) concentrations together with clinical parameters were documented daily during the first 7 days postoperative. The AVP response significantly differed between the three groups. Patients without SIRS had lower AVP concentrations than SIRS patients with (P = 0.001) or without shock (P = 0.003). Patients with SIRS and shock had higher AVP levels than patients with SIRS alone (P < 0.001). Arginine vasopressin decreased over time (P = 0.007) in all groups. At day 28, nonsurvivors had higher AVP levels than did survivors (P < 0.001). In SIRS patients without shock, serum osmolarity was indirectly associated with AVP levels, whereas mean arterial blood pressure and serum osmolarity were associated with AVP in SIRS patients with shock. Arginine vasopressin and copeptin correlated significantly with each other (P < 0.001; r = 0.76). In patients without hemofiltration, copeptin levels predicted 28-day mortality with high sensitivity and specificity. The postoperative AVP response in noncardiac surgery patients seems well maintained. The possibility that AVP plays a contributory role in the failure to restore vascular tone in patients with vasodilatory shock cannot be excluded but seems less important than in septic or postcardiotomy shock.

The vasopressin and copeptin response in patients with vasodilatory shock after cardiac surgery: a prospective, controlled study.

OBJECTIVE: To evaluate arginine vasopressin (AVP) and copeptin plasma concentrations in patients with vasodilatory shock after cardiac surgery. DESIGN: Prospective, controlled, clinical study. SETTING: Surgical intensive care unit and cardiac surgery ward in a tertiary university teaching hospital. PATIENTS AND PARTICIPANTS: Thirty-three critically ill patients with vasodilatory shock after cardiac surgery and ten control patients undergoing uncomplicated aorto-coronary bypass surgery. MEASUREMENTS AND RESULTS: Hemodynamic, laboratory and clinical data were recorded daily in all patients during the first 7 days after cardiac surgery. At the same time, points blood was withdrawn to determine plasma concentrations of AVP (radioimmunoassay) and copeptin (immunoluminometric assy). Standard tests, a mixed effects model and regression analyses were used for statistical analysis. The course of AVP was significantly different between groups (P < 0.001). While AVP concentrations were lower in the study group on the first postoperative day, they were higher than that in the control group from postoperative day 3 on. There was no difference in the postoperative AVP response between study patients with or without chronic angiotensin-converting enzyme inhibitor therapy. Except during continuous veno-venous hemofiltration, AVP and copeptin correlated significantly with each other (P < 0.001; r = 0.749). CONCLUSIONS: The AVP response to cardiac surgery is significantly different between patients with vasodilatory shock and patients undergoing uncomplicated aorto-coronary bypass surgery. Although no causative relationship between AVP concentrations and cardiovascular instability can be drawn from these results, our data support the hypothesis that inadequately low AVP plasma levels contribute to the failure to restore vascular tone in vasodilatory shock after cardiac surgery.

A comparison of the combination of epinephrine and vasopressin with lipid emulsion in a porcine model of asphyxial cardiac arrest after intravenous injection of bupivacaine.

BACKGROUND: In a porcine model, we compared the effect of the combination of vasopressin/epinephrine with that of a lipid emulsion on survival after bupivacaine-induced cardiac arrest. METHODS: After administration of 5 mg/kg of a 0.5% bupivacaine solution i.v., ventilation was interrupted for 2 +/- 0.5 (mean +/- SD) min until asystole occurred. Cardiopulmonary resuscitation (CPR) was initiated after 1 min of untreated cardiac arrest. After 2 min of CPR, 10 animals received, every 5 min, either vasopressin combined with epinephrine or 4 mL/kg of a 20% lipid emulsion. Three minutes after each drug administration, up to three countershocks (4, 4, and 6 J/kg) were administered; all subsequent shocks with 6 J/kg. Blood for determination of the plasma bupivacaine concentration was drawn throughout the experiment. RESULTS: In the vasopressor group, all five pigs survived, whereas none of five pigs in the lipid group had restoration of spontaneous circulation (P < 0.01). There was no significant difference between groups in the plasma concentration of total bupivacaine. CONCLUSION: In this model of a bupivacaine-induced cardiac arrest, the vasopressor combination of vasopressin and epinephrine compared with lipid emulsion resulted in higher coronary perfusion pressure during CPR and survival rates.

Anesthesia and its allied disciplines in the developing world: a nationwide survey of the Republic of Zambia.

BACKGROUND: Many surgical interventions worldwide are performed in developing countries. To improve survival of acutely and critically ill patients in these countries, basic problems and demands of anesthesia care need to be identified. Using this survey, we evaluated the current status of anesthesia and its allied disciplines (intensive care medicine, emergency medicine, and pain therapy) in the Republic of Zambia. METHODS: Questionnaires were sent to 87 hospitals registered at the Zambian Ministry of Health as performing minor or major surgery. The questionnaire consisted of 111 questions grouped into five sections: general hospital information, anesthesia, intensive care, emergency medicine, and pain therapy. RESULTS: Sixty-eight questionnaires could be statistically evaluated (78%). The most common operations were obstetric/gynecological and abdominal surgical procedures. Dissociative ketamine anesthesia was the technique most often used for general anesthesia (50%). Endotracheal intubation was performed in 10% of patients undergoing general anesthesia. In most hospitals (78%), anesthesia was administered by nonphysicians. Only 5 of 68 hospitals (7%) reported having an intensive care unit, with 29 beds to serve the entire country. Anesthesiologists play almost no role in emergency medicine and pain therapy. CONCLUSIONS: Anesthesia in the Republic of Zambia is a highly under-developed and under-resourced medical specialty.

Endogenous vasopressin and copeptin response in multiple trauma patients.

Endogenous arginine vasopressin (AVP) levels in multiple trauma patients are unknown. Arginine vasopressin is considered to play an important role in severe hemorrhage. In this prospective study, 87 multiple trauma patients (Injury Severity Score >15) and 50 healthy volunteers were enrolled. On admission to the emergency department (ED), demographic, clinical, and laboratory data were documented, and blood was sampled for determination of AVP (radioimmunosassay) and copeptin, a stable fragment of the AVP precursor (immunoluminometric assay). In patients requiring intensive care unit (ICU) therapy, blood and data sampling were repeated at 4, 6, and 24 h after ED admission. Linear logistic and mixed-effects regression analyses were used for statistical analysis. On ED admission, AVP plasma concentrations (43.2 +/- 84.9 pM) were significantly increased when compared with controls (0.92 +/- 0.44 pM, P < 0.001). Plethysmographic oxygen saturation was the only parameter independently associated with AVP (regression coefficient, -0.126; 95% confidence interval, -0.237 to -0.014; P = 0.03). No correlation was observed between AVP and survival (P = 0.62), hemodynamic variables (systolic arterial pressure, P = 0.24; MAP, P = 0.59; diastolic arterial pressure, P = 0.74; central venous pressure, P = 0.36), or brain trauma (P = 0.46). In ICU patients, AVP decreased during the first 24 h (P < 0.001) and was independently associated with heart rate (P = 0.02) and blood glucose (P = 0.009). Copeptin concentrations were correlated with AVP (r2 = 0.718, P < 0.001). In conclusion, AVP was significantly increased in multiple trauma patients and seems to be an integral part of the neuroendocrine response to severe injury. In ICU patients, AVP decreased to moderately elevated levels within 24 h after ED admission.

Comparison of two dose regimens of arginine vasopressin in advanced vasodilatory shock.

OBJECTIVE: To evaluate the effects of two arginine vasopressin (AVP) dose regimens (0.033 vs. 0.067 IU/min) on treatment efficacy, hemodynamic response, prevalence of adverse events, and changes in laboratory variables. DESIGN: Retrospective, controlled study. PATIENTS: A total of 78 patients with vasodilatory shock (mean norepinephrine dosage, 1.07 microg.kg-1.min-1; 95% confidence interval, 0.82-1.56 microg.kg-1.min-1). INTERVENTIONS: Supplementary infusion of AVP at 0.033 (n = 39) and 0.067 IU/min (n = 39). MEASUREMENTS AND MAIN RESULTS: Cardiocirculatory, laboratory, and clinical variables were evaluated and compared between groups before and at 0.5, 1, 4, 12, 24, 48, and 72 hrs after initiation of AVP. Treatment efficacy was assessed by the increase in mean arterial blood pressure and the extent of norepinephrine reduction during the first 24 hrs of AVP therapy. Standard tests and a mixed-effects model were used for statistical analysis. Although the relative increase in mean arterial pressure was comparable between groups (0.033 vs. 0.067 IU/min: 16.8 +/- 18.4 vs. 21.4 +/- 14.9 mm Hg, p = .24), norepinephrine could be reduced significantly more often in patients receiving 0.067 IU/min. AVP at 0.067 IU/min resulted in a higher mean arterial pressure (p < .001), lower central venous pressure (p = .001), lower mean pulmonary arterial pressure (p = .04), and lower norepinephrine requirements (p < .001) during the 72-hr observation period. Increases in liver enzymes occurred more often in patients treated with 0.033 IU/min (71.8% vs. 28.2%, p < .001). The prevalence of a decrease in cardiac index (69.2% vs. 53.8%, p = .24), decrease in platelet count (94.8% vs. 84.6%, p = .26), and increase in total bilirubin (48.7% vs. 71.8%, p = .06) was not significantly different between groups. Bilirubin levels (3.1 +/- 3.4 vs. 5.2 +/- 5.5 mg/dL, p = .04) and base deficit (-7.2 +/- 4.3 vs. -3.9 +/- 5.9 mmol/L, p = .005) were lower and arterial lactate concentrations higher (76 +/- 67 vs. 46 +/- 38 mg/dL, p < .001) in patients receiving 0.033 IU/min. CONCLUSIONS: AVP dosages of 0.067 IU/min seem to be more effective to reverse cardiovascular failure in vasodilatory shock requiring high norepinephrine dosages than 0.033 IU/min.

Arginine vasopressin during sinus rhythm: effects on haemodynamic variables, left anterior descending coronary artery cross sectional area and cardiac index, before and after inhibition of NO-synthase, in pigs.

UNLABELLED: We have shown previously that arginine vasopressin (AVP) given during sinus rhythm increases mean arterial blood pressure (MAP) and left anterior descending (LAD) coronary artery cross sectional area. AVP was assumed to result in vasodilatation via activation of the endothelial nitric oxide system. The purpose of the present study was to assess the effects of AVP before and after NO-inhibition. Nine domestic pigs were instrumented for measurement of haemodynamic variables using micromanometer-tipped catheters, and measurement of LAD coronary artery cross sectional area employing intravascular ultrasound (IVUS). Haemodynamic variables, LAD coronary artery cross sectional area and cardiac output were measured at baseline, 90 s and 5, 15, and 30 min after AVP (0.4 U kg (-1) IV) before and after blockade of nitric oxide synthase with N(G)-nitro L-arginine methyl ester (L-NAME). Compared with baseline, AVP significantly increased MAP after 90 s (89+/-4 versus 160+/-5 mm Hg), increased LAD coronary artery cross sectional area (11.3+/-1 versus 11.8+/-1 mm(2)) and decreased cardiac index (138+/-6 versus 53+/-6 mL/min kg(-1)). After blockade of nitric oxide synthase, AVP significantly increased MAP after 90 s (135+/-4 versus 151+/-3 mm Hg), increased LAD coronary artery cross sectional area (8.7+/-1 versus 8.9+/-1 mm(2)), and significantly decreased cardiac index (95+/-6 versus 29+/-4 mL/min kg (-1)). IMPLICATIONS: During sinus rhythm, AVP increased MAP and LAD coronary artery cross sectional area, but decreased cardiac index.

Arginine vasopressin in advanced cardiovascular failure during the post-resuscitation phase after cardiac arrest.

Arginine vasopressin (AVP) has been employed successfully during cardiopulmonary resuscitation, but there exist only few data about the effects of AVP infusion for cardiovascular failure during the post-cardiac arrest period. Cardiovascular failure is one of the main causes of death after successful resuscitation from cardiac arrest. Although the "post-resuscitation syndrome" has been described as a "sepsis-like" syndrome, there is little information about the haemodynamic response to AVP in advanced cardiovascular failure after cardiac arrest. In this retrospective study, haemodynamic and laboratory variables in 23 patients with cardiovascular failure unresponsive to standard haemodynamic therapy during the post-cardiac arrest period were obtained before, and 30 min, 1, 4, 12, 24, 48, and 72 h after initiation of a supplementary AVP infusion (4 IU/h). During the observation period, AVP significantly increased mean arterial blood pressure (58+/-14 to 75+/-19 mmHg, p < 0.001), and decreased noradrenaline (norepinephrine) (1.31+/-2.14 to 0.23+/-0.3 microg/kg/min, p = 0.03), adrenaline (epinephrine) (0.58+/-0.23 to 0.04+/-0.03 microg/kg/min, p = 0.001), and milrinone requirements (0.46+/-0.15 to 0.33+/-0.22 microg/kg/min, p < 0.001). Pulmonary capillary wedge pressure changed significantly (p < 0.001); an initial increase being followed by a decrease below baseline values. While arterial lactate concentrations (95+/-64 to 21+/-18 mg/dL, p < 0.001) and pH (7.27+/-0.14 to 7.4+/-0.14, p < 0.001) improved significantly, total bilirubin concentrations (1.12+/-0.95 to 3.04+/-3.79 mg/dL, p = 0.001) increased after AVP. There were no differences in the haemodynamic or laboratory response to AVP between survivors and non-survivors. In this study, advanced cardiovascular failure that was unresponsive to standard therapy could be reversed successfully with supplementary AVP infusion in >90% of patients surviving cardiac arrest.

Causes of death and determinants of outcome in critically ill patients.

INTRODUCTION: Whereas most studies focus on laboratory and clinical research, little is known about the causes of death and risk factors for death in critically ill patients. METHODS: Three thousand seven hundred patients admitted to an adult intensive care unit (ICU) were prospectively evaluated. Study endpoints were to evaluate causes of death and risk factors for death in the ICU, in the hospital after discharge from ICU, and within one year after ICU admission. Causes of death in the ICU were defined according to standard ICU practice, whereas deaths in the hospital and at one year were defined and grouped according to the ICD-10 (International Statistical Classification of Diseases and Related Health Problems) score. Stepwise logistic regression analyses were separately calculated to identify independent risk factors for death during the given time periods. RESULTS: Acute, refractory multiple organ dysfunction syndrome was the most frequent cause of death in the ICU (47%), and central nervous system failure (relative risk [RR] 16.07, 95% confidence interval [CI] 8.3 to 31.4, p < 0.001) and cardiovascular failure (RR 11.83, 95% CI 5.2 to 27.1, p < 0.001) were the two most important risk factors for death in the ICU. Malignant tumour disease and exacerbation of chronic cardiovascular disease were the most frequent causes of death in the hospital (31.3% and 19.4%, respectively) and at one year (33.2% and 16.1%, respectively). CONCLUSION: In this primarily surgical critically ill patient population, acute or chronic multiple organ dysfunction syndrome prevailed over single-organ failure or unexpected cardiac arrest as a cause of death in the ICU. Malignant tumour disease and chronic cardiovascular disease were the most important causes of death after ICU discharge.

Copeptin and arginine vasopressin concentrations in critically ill patients.

CONTEXT: Determination of arginine vasopressin (AVP) concentrations may be helpful to guide therapy in critically ill patients. A new assay analyzing copeptin, a stable peptide derived from the AVP precursor, has been introduced. OBJECTIVE: Our objective was to determine plasma copeptin concentrations. DESIGN: We conducted a post hoc analysis of plasma samples and data from a prospective study. SETTING: The setting was a 12-bed general and surgical intensive care unit (ICU) in a tertiary university teaching hospital. PATIENTS: Our subjects were 70 healthy volunteers and 157 ICU patients with sepsis, with systemic inflammatory response syndrome (SIRS), and after cardiac surgery. INTERVENTIONS: There were no interventions. MAIN OUTCOME MEASURES: Copeptin plasma concentrations, demographic data, AVP plasma concentrations, and a multiple organ dysfunction syndrome score were documented 24 h after ICU admission. RESULTS: AVP (P < 0.001) and copeptin (P < 0.001) concentrations were significantly higher in ICU patients than in controls. Patients after cardiac surgery had higher AVP (P = 0.003) and copeptin (P = 0.003) concentrations than patients with sepsis or SIRS. Independent of critical illness, copeptin and AVP correlated highly significantly with each other. Critically ill patients with sepsis and SIRS exhibited a significantly higher ratio of copeptin/AVP plasma concentrations than patients after cardiac surgery (P = 0.012). The American Society of Anesthesiologists' classification (P = 0.046) and C-reactive protein concentrations (P = 0.006) were significantly correlated with the copeptin/AVP ratio. CONCLUSIONS: Plasma concentrations of copeptin and AVP in healthy volunteers and critically ill patients correlate significantly with each other. The ratio of copeptin/AVP plasma concentrations is increased in patients with sepsis and SIRS, suggesting that copeptin may overestimate AVP plasma concentrations in these patients.