Early non-invasive cardiac output monitoring in hemodynamically unstable intensive care patients: A multi-center randomized controlled trial

Introduction Acute hemodynamic instability increases morbidity and mortality. We investigated whether early non-invasive cardiac output monitoring enhances hemodynamic stabilization and improves outcome. Methods A multicenter, randomized controlled trial was conducted in three European university hospital intensive care units in 2006 and 2007. A total of 388 hemodynamically unstable patients identified during their first six hours in the intensive care unit (ICU) were randomized to receive either non-invasive cardiac output monitoring for 24 hrs (minimally invasive cardiac output/MICO group; n = 201) or usual care (control group; n = 187). The main outcome measure was the proportion of patients achieving hemodynamic stability within six hours of starting the study. Results The number of hemodynamic instability criteria at baseline (MICO group mean 2.0 (SD 1.0), control group 1.8 (1.0); P = .06) and severity of illness (SAPS II score; MICO group 48 (18), control group 48 (15); P = .86)) were similar. At 6 hrs, 45 patients (22%) in the MICO group and 52 patients (28%) in the control group were hemodynamically stable (mean difference 5%; 95% confidence interval of the difference -3 to 14%; P = .24). Hemodynamic support with fluids and vasoactive drugs, and pulmonary artery catheter use (MICO group: 19%, control group: 26%; P = .11) were similar in the two groups. The median length of ICU stay was 2.0 (interquartile range 1.2 to 4.6) days in the MICO group and 2.5 (1.1 to 5.0) days in the control group (P = .38). The hospital mortality was 26% in the MICO group and 21% in the control group (P = .34). Conclusions Minimally-invasive cardiac output monitoring added to usual care does not facilitate early hemodynamic stabilization in the ICU, nor does it alter the hemodynamic support or outcome. Our results emphasize the need to evaluate technologies used to measure stroke volume and cardiac output--especially their impact on the process of care--before any large-scale outcome studies are attempted.

Comparison of calibrated and uncalibrated arterial pressure-based cardiac output monitors during orthotopic liver transplantation

Arterial pressure-based cardiac output monitors (APCOs) are increasingly used as alternatives to thermodilution. Validation of these evolving technologies in high-risk surgery is still ongoing. In liver transplantation, FloTrac-Vigileo (Edwards Lifesciences) has limited correlation with thermodilution, whereas LiDCO Plus (LiDCO Ltd.) has not been tested intraoperatively. Our goal was to directly compare the 2 proprietary APCO algorithms as alternatives to pulmonary artery catheter thermodilution in orthotopic liver transplantation (OLT). The cardiac index (CI) was measured simultaneously in 20 OLT patients at prospectively defined surgical landmarks with the LiDCO Plus monitor (CI(L)) and the FloTrac-Vigileo monitor (CI(V)). LiDCO Plus was calibrated according to the manufacturer's instructions. FloTrac-Vigileo did not require calibration. The reference CI was derived from pulmonary artery catheter intermittent thermodilution (CI(TD)). CI(V)-CI(TD) bias ranged from -1.38 (95% confidence interval = -2.02 to -0.75 L/minute/m(2), P = 0.02) to -2.51 L/minute/m(2) (95% confidence interval = -3.36 to -1.65 L/minute/m(2), P < 0.001), and CI(L)-CI(TD) bias ranged from -0.65 (95% confidence interval = -1.29 to -0.01 L/minute/m(2), P = 0.047) to -1.48 L/minute/m(2) (95% confidence interval = -2.37 to -0.60 L/minute/m(2), P < 0.01). For both APCOs, bias to CI(TD) was correlated with the systemic vascular resistance index, with a stronger dependence for FloTrac-Vigileo. The capability of the APCOs for tracking changes in CI(TD) was assessed with a 4-quadrant plot for directional changes and with receiver operating characteristic curves for specificity and sensitivity. The performance of both APCOs was poor in detecting increases and fair in detecting decreases in CI(TD). In conclusion, the calibrated and uncalibrated APCOs perform differently during OLT. Although the calibrated APCO is less influenced by changes in the systemic vascular resistance, neither device can be used interchangeably with thermodilution to monitor cardiac output during liver transplantation.

Influence of water immersion, water gymnastics and swimming on cardiac output in patients with heart failure

Background Whole-body water immersion leads to a significant shift of blood from the periphery into the intra-thoracic circulation, followed by an increase in central venous pressure and heart volume. In patients with severely reduced left ventricular function, this hydrostatically in-duced volume shift might overstrain the cardiovascular adaptive mechanisms and lead to cardiac decompensation. The aim of this study is to assess the hemodynamic response to water immer-sion, gymnastics and swimming in patients with heart failure (CHF). Methods We examined 10 patients with compensated CHF (62.9 +/- 6.3 years, EF 31.5 +/- 4.1%, peak VO2 19.4 +/- 2.8 ml/kg/min.), 10 patients with coronary artery disease (CAD) but preserved left ventricular function (57.2 +/- 5.6 years, EF 63.9 +/- 5.5%, peak VO2 28.0 +/- 6.3 ml/kg/min.) and 10 healthy subjects (32.8 +/- 7.2 years, peak VO2 45.6 +/- 6.0 ml/kg/min.). Hemodynamic response to thermo-neutral (32 degrees C) water immersion and exercise was measured using a non-invasive foreign gas rebreathing method during stepwise water immersion, water gymnastics and swimming. Results Water immersion up to the chest increased cardiac index by 19% in healthy subjects, by 21% in CAD patients and 16% in CHF patients. While some CHF patients showed a decrease of stroke volume during immersion, all subjects were able to increase cardiac index (by 87% in healthy subjects, 77% in CAD patients and 53% in CHF patients). Oxygen uptake during swim-ming was 9.7 +/- 3.3 ml/kg/min. in CHF patients, 12.4 +/- 3.5 ml/kg/min. in CAD patients and 13.9 +/- 4.0 ml/kg/min. in healthy subjects. Conclusions Patients with severely reduced left ventricular function but stable clinical conditions and a minimal peak VO2 of at least 15 ml/kg/min. during a symptom-limited exercise stress test tolerate water immersion and swimming in thermo-neutral water well. Although cardiac in-dex and oxygen uptake are lower compared with CAD patients with preserved left ventricular function and healthy controls, these patients are able to increase cardiac index adequately during water immersion and swimming.

Arterio-venous gradients of free energy change for assessment of systemic and splanchnic perfusion in cardiac surgery patients

OBJECTIVE: Adequacy of organ perfusion depends on sufficient oxygen supply in relation to the metabolic needs. The aim of this study was to evaluate the relationship between gradients of free energy change, and the more commonly used parameter for the evaluation of the adequacy of organ perfusion, such as oxygen-extraction in patients undergoing valve replacement surgery using normothermic cardiopulmonary bypass (CPB). METHODS: In 43 cardiac patients, arterial, mixed venous, and hepato-venous blood samples were taken synchronously after induction of anaesthesia (preCPB), during CPB, and 2 and 7 h after admission to the intensive care unit (ICU+2, ICU+7). Blood gas analysis, cardiac output, and hepato-splanchnic blood flow were measured. Free energy change gradients between mixed venous and arterial (-deltadeltaG(v - a)) and hepato-venous and arterial (-deltadeltaG(hv - a)) compartments were calculated. MEASUREMENTS AND RESULTS: Cardiac index (CI) increased from 1.9 (0.7) to 2.8 (1.3) L/min/m (median, inter-quartile range) (p = 0.001), and hepato-splanchnic blood flow index (HBFI) from 0.6 (0.22) to 0.8 (0.53) L/min/m (p = 0.001). Despite increasing flow, systemic oxygen extraction increased after CPB from 24 (10)% to 35 (10)% at ICU+2 (p = 0.002), and splanchnic oxygen extraction increased during CPB from 37 (19)% to 52 (14)% (p = 0.001), and remained high thereafter. After CPB, high splanchnic and systemic gradients of free energy change gradients were associated with high splanchnic and systemic oxygen extraction, respectively (p = 0.001, 0.033, respectively). CONCLUSION: Gradients of free energy change may be helpful in characterising adequacy of perfusion in cardiac surgery patients independently from measurements or calculations of data from oxygen transport.

ECG-triggered muscular counterpulsation for treatment of low cardiac output

BACKGROUND: Skeletal muscular counterpulsation (MCP) has been used as a new noninvasive technique for treatment of low cardiac output. The MCP method is based on ECG-triggered skeletal muscle stimulation. The purpose of the present study was to evaluate acute hemodynamic changes induced by MCP in the experimental animal. METHODS: Eight anaesthetized pigs (43+/-4 kg) were studied at rest and after IV â-blockade (10 mg propranolol) before and after MCP. Muscular counterpulsation was performed on both thighs using trains (75 ms duration) of multiple biphasic electrical impulses with a width of 1 ms and a frequency of 200 Hz at low (10 V) and high (30 V) amplitude. ECG-triggering was used to synchronize stimulation to a given time point. LV pressure-volume relations were determined using the conductance catheter. After baseline measurements, MCP was carried out for 10 minutes at low and high stimulation amplitude. The optimal time point for MCP was determined from LV pressure-volume loops using different stimulation time points during systole and diastole. Best results were observed during end-systole and, therefore, this time point was used for stimulation. RESULTS: Under control conditions, MCP was associated with a significant decrease in pulmonary vascular resistance (-18%), a decrease in systemic vascular resistance (-11%) and stroke work index (-4%), whereas cardiac index (+2%) and ejection fraction (+6%) increased slightly. Pressure-volume loops showed a leftward shift with a decrease in end-systolic volume. After â-blockade, cardiac function decreased (HR, MAP, EF, dP/dt max), but it improved with skeletal muscle stimulation (HR +10% and CI +17%, EF +5%). There was a significant decrease in pulmonary (-19%) and systemic vascular resistance (-29%). CONCLUSIONS: In the animal model, ECG-triggered skeletal muscular counterpulsation is associated with a significant improvement in cardiac function at baseline and after IV â-blockade. Thus, MCP represents a new, non-invasive technique which improves cardiac function by diastolic compression of the peripheral arteries and veins, with a decrease in systemic vascular resistance and increase in cardiac output.

Evaluation of the Hepa Wash® treatment in pigs with acute liver failure

BACKGROUND Mortality of patients with acute liver failure (ALF) is still unacceptably high. Available liver support systems are still of limited success at improving survival. A new type of albumin dialysis, the Hepa Wash® system, was newly introduced. We evaluated the new liver support system as well as the Molecular Adsorbent Recycling System (MARS) in an ischemic porcine model of ALF. METHODS In the first study animals were randomly allocated to control (n=5) and Hepa Wash (n=6) groups. In a further pilot study, two animals were treated with the MARS-system. All animals received the same medical and surgical procedures. An intraparenchymal intracranial pressure was inserted. Hemodynamic monitoring and goal-directed fluid therapy using the PiCCO system was done. Animals underwent functional end-to-side portacaval shunt and ligation of hepatic arteries. Treatment with albumin dialysis was started after fall of cerebral perfusion pressure to 45 mmHg and continued for 8 h. RESULTS All animals in the Hepa Wash group survived the 13-hour observation period, except for one that died after stopping treatment. Four of the control animals died within this period (p=0.03). Hepa Wash significantly reduced impairment of cerebral perfusion pressure (23±2 vs. 10±3 mmHg, p=0.006) and mean arterial pressure (37±1 vs. 24±2 mmHg, p=0.006) but had no effect on intracranial pressure (14±1 vs. 15±1 mmHg, p=0.72). Hepa Wash also enhanced cardiac index (4.94±0.32 vs. 3.36±0.25 l/min/m2, p=0.006) and renal function (urine production, 1850 ± 570 vs. 420 ± 180 ml, p=0.045) and eliminated water soluble (creatinine, 1.3±0.2 vs. 3.2±0.3 mg/dl, p=0.01; ammonia 562±124 vs. 1382±92 μg/dl, p=0.006) and protein-bound toxins (nitrate/nitrite 5.54±1.57 vs. 49.82±13.27 μmol/l, p=0.01). No adverse events that could be attributed to the Hepa Wash treatment were observed. CONCLUSIONS Hepa Wash was a safe procedure and improved multiorgan system failure in pigs with ALF. The survival benefit could be the result of ameliorating different organ functions in association with the detoxification capacity of water soluble and protein-bound toxins.

Non-invasive hemodynamic monitoring in trauma patients.

BACKGROUND The assessment of hemodynamic status is a crucial task in the initial evaluation of trauma patients. However, blood pressure and heart rate are often misleading, as multiple variables may impact these conventional parameters. More reliable methods such as pulmonary artery thermodilution for cardiac output measuring would be necessary, but its applicability in the Emergency Department is questionable due to their invasive nature. Non-invasive cardiac output monitoring devices may be a feasible alternative. METHODS A systematic literature review was conducted. Only studies that explicitly investigated non-invasive hemodynamic monitoring devices in trauma patients were considered. RESULTS A total of 7 studies were identified as suitable and were included into this review. These studies evaluated in a total of 1,197 trauma patients the accuracy of non-invasive hemodynamic monitoring devices by comparing measurements to pulmonary artery thermodilution, which is the gold standard for cardiac output measuring. The correlation coefficients r between the two methods ranged from 0.79 to 0.92. Bias and precision analysis ranged from -0.02 +/- 0.78 l/min/m(2) to -0.14 +/- 0.73 l/min/m(2). Additionally, data on practicality, limitations and clinical impact of the devices were collected. CONCLUSION The accuracy of non-invasive cardiac output monitoring devices in trauma patients is broadly satisfactory. As the devices can be applied very early in the shock room or even preclinically, hemodynamic shock may be recognized much earlier and therapeutic interventions could be applied more rapidly and more adequately. The devices can be used in the daily routine of a busy ED, as they are non-invasive and easy to master.

Role of selective V2-receptor-antagonism in septic shock: a randomized, controlled, experimental study

ABSTRACT : INTRODUCTION : V2-receptor (V2R) stimulation potentially aggravates sepsis-induced vasodilation, fluid accumulation and microvascular thrombosis. Therefore, the present study was performed to determine the effects of a first-line therapy with the selective V2R-antagonist (Propionyl1-D-Tyr(Et)2-Val4-Abu6-Arg8,9)-Vasopressin on cardiopulmonary hemodynamics and organ function vs. the mixed V1aR/V2R-agonist arginine vasopressin (AVP) or placebo in an established ovine model of septic shock. METHODS : After the onset of septic shock, chronically instrumented sheep were randomly assigned to receive first-line treatment with the selective V2R-antagonist (1 g/kg per hour), AVP (0.05 g/kg per hour), or normal saline (placebo, each n = 7). In all groups, open-label norepinephrine was additionally titrated up to 1 g/kg per minute to maintain mean arterial pressure at 70 ± 5 mmHg, if necessary. RESULTS : Compared to AVP- and placebo-treated animals, the selective V2R-antagonist stabilized cardiopulmonary hemodynamics (mean arterial and pulmonary artery pressure, cardiac index) as effectively and increased intravascular volume as suggested by higher cardiac filling pressures. Furthermore, left ventricular stroke work index was higher in the V2R-antagonist group than in the AVP group. Notably, metabolic (pH, base excess, lactate concentrations), liver (transaminases, bilirubin) and renal (creatinine and blood urea nitrogen plasma levels, urinary output, creatinine clearance) dysfunctions were attenuated by the V2R-antagonist when compared with AVP and placebo. The onset of septic shock was associated with an increase in AVP plasma levels as compared to baseline in all groups. Whereas AVP plasma levels remained constant in the placebo group, infusion of AVP increased AVP plasma levels up to 149 ± 21 pg/mL. Notably, treatment with the selective V2R-antagonist led to a significant decrease of AVP plasma levels as compared to shock time (P < 0.001) and to both other groups (P < 0.05 vs. placebo; P < 0.001 vs. AVP). Immunohistochemical analyses of lung tissue revealed higher hemeoxygenase-1 (vs. placebo) and lower 3-nitrotyrosine concentrations (vs. AVP) in the V2R-antagonist group. In addition, the selective V2R-antagonist slightly prolonged survival (14 ± 1 hour) when compared to AVP (11 ± 1 hour, P = 0.007) and placebo (11 ± 1 hour, P = 0.025). CONCLUSIONS : Selective V2R-antagonism may represent an innovative therapeutic approach to attenuate multiple organ dysfunction in early septic shock.

Effects of epinephrine, norepinephrine, and phenylephrine on microcirculatory blood flow in the gastrointestinal tract in sepsis

OBJECTIVE: The use of vasopressors for treatment of hypotension in sepsis may have adverse effects on microcirculatory blood flow in the gastrointestinal tract. The aim of this study was to measure the effects of three vasopressors, commonly used in clinical practice, on microcirculatory blood flow in multiple abdominal organs in sepsis. DESIGN: Random order, cross-over design. SETTING: University laboratory. SUBJECTS: Eight sedated and mechanically ventilated pigs. INTERVENTIONS: Pigs were exposed to fecal peritonitis-induced septic shock. Mesenteric artery flow was measured using ultrasound transit time flowmetry. Microcirculatory flow was measured in gastric, jejunal, and colon mucosa; jejunal muscularis; and pancreas, liver, and kidney using multiple-channel laser Doppler flowmetry. Each animal received a continuous intravenous infusion of epinephrine, norepinephrine, and phenylephrine in a dose increasing mean arterial pressure by 20%. The animals were allowed to recover for 60 mins after each drug before the next was started. MEASUREMENTS AND MAIN RESULTS: During infusion of epinephrine (0.8 +/- 0.2 mug/kg/hr), mean arterial pressure increased from 66 +/- 5 to 83 +/- 5 mm Hg and cardiac index increased by 43 +/- 9%. Norepinephrine (0.7 +/- 0.3 mug/kg/hr) increased mean arterial pressure from 70 +/- 4 to 87 +/- 5 mm Hg and cardiac index by 41 +/- 8%. Both agents caused a significant reduction in superior mesenteric artery flow (11 +/- 4%, p < .05, and 26 +/- 6%, p < .01, respectively) and in microcirculatory blood flow in the jejunal mucosa (21 +/- 5%, p < .01, and 23 +/- 3%, p < .01, respectively) and in the pancreas (16 +/- 3%, p < .05, and 8 +/- 3%, not significant, respectively). Infusion of phenylephrine (3.1 +/- 1.0 mug/kg/min) increased mean arterial pressure from 69 +/- 5 to 85 +/- 6 mm Hg but had no effects on systemic, regional, or microcirculatory flow except for a 30% increase in jejunal muscularis flow (p < .01). CONCLUSIONS: Administration of the vasopressors phenylephrine, epinephrine, and norepinephrine failed to increase microcirculatory blood flow in most abdominal organs despite increased perfusion pressure and-in the case of epinephrine and norepinephrine-increased systemic blood flow. In fact, norepinephrine and epinephrine appeared to divert blood flow away from the mesenteric circulation and decrease microcirculatory blood flow in the jejunal mucosa and pancreas. Phenylephrine, on the other hand, appeared to increase blood pressure without affecting quantitative blood flow or distribution of blood flow.

Effects of thoracic epidural anesthesia on hemodynamics and global oxygen transport in ovine endotoxemia

Besides providing effective analgesia, thoracic epidural anesthesia (TEA) has been shown to decrease perioperative morbidity and mortality. Because of its vasodilatory properties in association with the sympathetic blockade, however, TEA may potentially aggravate cardiovascular dysfunctions resulting from sepsis and systemic inflammatory response syndrome. The objective of the present study was to assess the effects of TEA on hemodynamics, global oxygen transport, and renal function in ovine endotoxemia. After a baseline measurement in healthy sheep (n = 18), Salmonella typhosa endotoxin was centrally infused at incremental doses to induce and maintain a hypotensive-hypodynamic circulation using an established protocol. The animals were then randomly assigned to one of two groups. In the treatment group, continuous TEA was initiated with 0.1 mL.kg of 0.125% bupivacaine at the onset of endotoxemia and maintained with 0.1 mL.kg.h. In the control group, the same amount of isotonic sodium chloride solution was injected through the epidural catheter. In the animals surviving the entire experiment (n = 7 per group), cardiac index and mean arterial pressure decreased in a dose-dependent manner during endotoxin infusion. In the TEA group, neither systemic hemodynamics nor global oxygen transport were impaired beyond the changes caused by endotoxemia itself. Urinary output was increased in the TEA group as compared with the control group (P < 0.05). In this model of endotoxic shock, TEA improved renal perfusion without affecting cardiopulmonary hemodynamics and global oxygen transport.

[Arginine-vasopressin in septic and vasodilatorial shock]

Current therapy of septic/vasodilatory cardiovascular failure includes volume resuscitation and infusion of inotropic and vasopressor agents. Norepinephrine is the first-line vasoconstrictor, and can stabilize hemodynamic variables in most patients. Nonetheless, irreversible cardiovascular failure which is resistant to conventional hemodynamic therapies still is the main cause of death in patients with severe sepsis and septic shock. In such advanced, catecholamine-resistant shock states, arginine-vasopressin (AVP) has repeatedly caused an increase in mean arterial blood pressure, a decrease in toxic norepinephrine-dosages, as well as further beneficial hemodynamic, endocrinologic and renal effects. Although AVP exerted negative inotropic effects in previous clinical trials and in selected animal experiments, a continuous low-dose AVP infusion during advanced septic/vasodilatory shock caused a decrease in cardiac index only in patients with a hyperdynamic circulation. Adverse effects on gastrointestinal circulation and the systemic microcirculation can not be excluded, but have not yet been confirmed in clinical prospective trials. Negative side effects of a supplementary AVP therapy are an increase in total bilirubin concentrations, and a decrease in platelet count. A transient increase in hepatic transaminases during AVP infusion is most likely related to preceding hypotensive episodes. Important points which must be considered when using AVP as a "rescue vasopressor" in septic/vasodilatory shock states are: 1) AVP infusion only in advanced shock states that can not be adequately reversed by conventional hemodynamic therapy (e.g. norepinephrine >0,5-0,6 mug/kg/min), 2) presence of normovolemia, 3) AVP infusion only in combination with norepinephrine, 4) strict avoidance of bolus injections and dosages >4 IU/h. Effects of a supplementary AVP infusion in advanced vasodilatory shock on survival are currently examined in a large, prospective multicenter trial in North America and Australia.

Vasopressin in vasodilatory shock: ensure organ blood flow, but take care of the heart!

Supplementary arginine vasopressin infusion in advanced vasodilatory shock may be accompanied by a decrease in cardiac index and systemic oxygen transport capacity in approximately 40% of patients. While a reduction of cardiac output most frequently occurs in patients with hyperdynamic circulation, it is less often observed in patients with low cardiac index. Infusion of inotropes, such as dobutamine, may be an effective strategy to restore systemic blood flow. However, when administering inotropic drugs, systemic blood flow should be increased to adequately meet systemic demands (assessed by central or mixed venous oxygen saturation) without putting an excessive beta-adrenergic stress on the heart. Overcorrection of cardiac index to hyperdynamic values with inotropes places myocardial oxygen supply at significant risk.

Rapid restoration of microcirculatory blood flow with hyperviscous and hyperoncotic solutions lowers the transfusion trigger in resuscitation from hemorrhagic shock

Resuscitation from hemorrhagic shock relies on fluid retransfusion. However, the optimal properties of the fluid have not been established. The aim of the present study was to test the influence of the concentration of hydroxyethyl starch (HES) solution on plasma viscosity and colloid osmotic pressure (COP), systemic and microcirculatory recovery, and oxygen delivery and consumption after resuscitation, which were assessed in the hamster chamber window preparation by intravital microscopy. Awake hamsters were subjected to 50% hemorrhage and were resuscitated with 25% of the estimated blood volume with 5%, 10%, or 20% HES solution. The increase in concentration led to an increase in COP (from 20 to 70 and 194 mmHg) and viscosity (from 1.7 to 3.8 and 14.4 cP). Cardiac index and microcirculatory and metabolic recovery were improved with HES 10% and 20% when compared with 5% HES. Oxygen delivery and consumption in the dorsal skinfold chamber was more than doubled with HES 10% and 20% when compared with HES 5%. This was attributed to the beneficial effect of restored or increased plasma COP and plasma viscosity as obtained with HES 10% and 20%, leading to improved microcirculatory blood flow values early in the resuscitation period. The increase in COP led to an increase in blood volume as shown by a reduction in hematocrit. Mean arterial pressure was significantly improved in animals receiving 10% and 20% solutions. In conclusion, the present results show that the increase in the concentration of HES, leading to hyperoncotic and hyperviscous solutions, is beneficial for resuscitation from hemorrhagic shock because normalization of COP and viscosity led to a rapid recovery of microcirculatory parameters.

Effects of vasopressin on microcirculatory blood flow in the gastrointestinal tract in anesthetized pigs in septic shock

BACKGROUND: Vasopressin increases arterial pressure in septic shock even when alpha-adrenergic agonists fail. The authors studied the effects of vasopressin on microcirculatory blood flow in the entire gastrointestinal tract in anesthetized pigs during early septic shock. METHODS: Thirty-two pigs were intravenously anesthetized, mechanically ventilated, and randomly assigned to one of four groups (n=8 in each; full factorial design). Group S (sepsis) and group SV (sepsis-vasopressin) were made septic by fecal peritonitis. Group C and group V were nonseptic control groups. After 300 min, group V and group SV received intravenous infusion of 0.06 U.kg.h vasopressin. In all groups, cardiac index and superior mesenteric artery flow were measured. Microcirculatory blood flow was recorded with laser Doppler flowmetry in both mucosa and muscularis of the stomach, jejunum, and colon. RESULTS: While vasopressin significantly increased arterial pressure in group SV (P<0.05), superior mesenteric artery flow decreased by 51+/-16% (P<0.05). Systemic and mesenteric oxygen delivery and consumption decreased and oxygen extraction increased in the SV group. Effects on the microcirculation were very heterogeneous; flow decreased in the stomach mucosa (by 23+/-10%; P<0.05), in the stomach muscularis (by 48+/-16%; P<0.05), and in the jejunal mucosa (by 27+/-9%; P<0.05), whereas no significant changes were seen in the colon. CONCLUSION: Vasopressin decreased regional flow in the superior mesenteric artery and microcirculatory blood flow in the upper gastrointestinal tract. This reduction in flow and a concomitant increase in the jejunal mucosa-to-arterial carbon dioxide gap suggest compromised mucosal blood flow in the upper gastrointestinal tract in septic pigs receiving low-dose vasopressin.

Methylprednisolone Fails to Preserve Pulmonary Surfactant and Blood-Air Barrier Integrity in a Porcine Cardiopulmonary Bypass Model

BACKGROUND: Pulmonary inflammation after cardiac surgery with cardiopulmonary bypass (CPB) has been linked to respiratory dysfunction and ultrastructural injury. Whether pretreatment with methylprednisolone (MP) can preserve pulmonary surfactant and blood-air barrier, thereby improving pulmonary function, was tested in a porcine CPB-model. MATERIALS AND METHODS: After randomizing pigs to placebo (PLA; n = 5) or MP (30 mg/kg, MP; n = 5), animals were subjected to 3 h of CPB with 1 h of cardioplegic cardiac arrest. Hemodynamic data, plasma tumor necrosis factor-alpha (TNF-alpha, ELISA), and pulmonary function parameters were assessed before, 15 min after CPB, and 8 h after CPB. Lung biopsies were analyzed for TNF-alpha (Western blot) or blood-air barrier and surfactant morphology (electron microscopy, stereology). RESULTS: Systemic TNF-alpha increased and cardiac index decreased at 8 h after CPB in PLA (P < 0.05 versus pre-CPB), but not in MP (P < 0.05 versus PLA). In both groups, at 8 h after CPB, PaO(2) and PaO(2)/FiO(2) were decreased and arterio-alveolar oxygen difference and pulmonary vascular resistance were increased (P < 0.05 versus baseline). Postoperative pulmonary TNF-alpha remained unchanged in both groups, but tended to be higher in PLA (P = 0.06 versus MP). The volume fraction of inactivated intra-alveolar surfactant was increased in PLA (58 +/- 17% versus 83 +/- 6%) and MP (55 +/- 18% versus 80 +/- 17%) after CPB (P < 0.05 versus baseline for both groups). Profound blood-air barrier injury was present in both groups at 8 h as indicated by an increased blood-air barrier integrity score (PLA: 1.28 +/- 0.03 versus 1.70 +/- 0.1; MP: 1.27 +/- 0.08 versus 1.81 +/- 0.1; P < 0.05). CONCLUSION: Despite reduction of the systemic inflammatory response and pulmonary TNF-alpha generation, methylprednisolone fails to decrease pulmonary TNF-alpha and to preserve pulmonary surfactant morphology, blood-air barrier integrity, and pulmonary function after CPB.