Autologous red blood cell transfusion does not result in a more profound increase in pulmonary capillary wedge pressure compared to saline in critically ill patients: A randomized crossover trial.

BACKGROUND AND OBJECTIVES: Transfusion-associated circulatory overload (TACO) is a major cause of severe transfusion-related morbidity. Transfusion of red blood cells (RBCs) has been shown to induce hydrostatic pressure overload. It is unclear which product-specific factors contribute. We set out to determine the effect of autologous RBC transfusion versus saline on pulmonary capillary wedge pressure (PCWP) change. MATERIALS AND METHODS: In a randomized crossover trial, patients who had undergone coronary bypass surgery were allocated to treatment post-operatively in the intensive care unit with either an initial 300 ml autologous RBC transfusion (salvaged during surgery) or 300 ml saline infusion first, followed by the other. Primary outcome was the difference in PCWP change. Secondary outcome measures were the difference in extra-vascular lung water index (EVLWI) and pulmonary vascular permeability index (PVPI). RESULTS: Change in PCWP was not higher after autologous RBC transfusion compared to saline (ΔPCWP 0.3 ± 0.4 vs. 0.1 ± 0.4 mmHg). ΔEVLWI and ΔPVPI were significantly decreased after autologous RBC transfusion compared to saline (ΔEVLWI -1.6 ± 0.6 vs. 0.2 ± 0.4, p = 0.02; ΔPVPI -0.3 ± 0.1 vs. 0.0 ± 0.1, p = 0.01). Haemodynamic variables and colloid osmotic pressure were not different for autologous RBC transfusion versus saline. CONCLUSION: Transfusion of autologous RBCs did not result in a more profound increase in PCWP compared to saline. RBC transfusion resulted in a decrease of EVLWI and PVPI compared to saline. Our data suggest that transfusing autologous RBCs may lead to less pulmonary oedema compared to saline. Future studies with allogeneic RBCs are needed to investigate other factors that may mediate the increase of PCWP, resulting in TACO.

Effects of Oral Supplementation With Nitrate-Rich Beetroot Juice in Patients With Pulmonary Arterial Hypertension-Results From BEET-PAH, an Exploratory Randomized, Double-Blind, Placebo-Controlled, Crossover Study.

BACKGROUND: The nitrate-nitrite-nitric oxide (NO) pathway may represent a potential therapeutic target in patients with pulmonary arterial hypertension (PAH). We explored the effects of dietary nitrate supplementation, with the use of nitrate-rich beetroot juice (BRJ), in patients with PAH. METHODS AND RESULTS: We prospectively studied 15 patients with PAH in an exploratory randomized, double-blind, placebo-controlled, crossover trial. The patients received nitrate-rich beetroot juice (∼16 mmol nitrate per day) and placebo in 2 treatment periods of 7 days each. The assessments included; exhaled NO and NO flow-independent parameters (alveolar NO and bronchial NO flux), plasma and salivary nitrate and nitrite, biomarkers and metabolites of the NO-system, N-terminal pro-B-type natriuretic peptide, echocardiography, ergospirometry, diffusing capacity of the lung for carbon monoxide, and the 6-minute walk test. Compared with placebo ingestion of BRJ resulted in increases in; fractional exhaled NO at all flow-rates, alveolar NO concentrations and bronchial NO flux, and plasma and salivary levels of nitrate and nitrite. Plasma ornithine levels decreased and indices of relative arginine availability increased after BRJ compared to placebo. A decrease in breathing frequency was observed during ergospirometry after BRJ. A tendency for an improvement in right ventricular function was observed after ingestion of BRJ. In addition a tendency for an increase in the peak power output to peak oxygen consumption ratio (W peak/VO2 peak) was observed, which became significant in patients reaching an increase of plasma nitrite >30% (responders). CONCLUSIONS: BRJ administered for 1 week increases pulmonary NO production and the relative arginine bioavailability in patients with PAH, compared with placebo. An increase in the W peak/VO2 peak ratio was observed after BRJ ingestion in plasma nitrite responders. These findings indicate that supplementation with inorganic nitrate increase NO synthase-independent NO production from the nitrate-nitrite-NO pathway.

Acute hemodynamic changes by breathing hypoxic and hyperoxic gas mixtures in pulmonary arterial and chronic thromboembolic pulmonary hypertension.

BACKGROUND: There is insufficient evidence to counsel patients with pulmonary hypertension undergoing altitude or air travel. We thus aimed to study hemodynamic response of patients with pulmonary arterial or chronic thromboembolic pulmonary hypertension (PAH/CTEPH) during changes in inspiratory oxygen partial pressure. METHODS AND RESULTS: Consecutive patients undergoing right heart catheterization had hemodynamic assessments whilst breathing ambient air (normoxia, FiO2 0.21, at altitude 490 m), nitrogen-enriched air (hypoxia, FiO2 0.16, simulated altitude 2600 m) and oxygen (hyperoxia, FiO2 1.0), each for 10 min. Data from patients with PAH/CTEPH with mean pulmonary artery pressure (mPAP) ≥25 mmHg, pulmonary artery wedge pressure ≤15 mmHg, were compared to data from controls, mPAP <20 mmHg. 28 PAH/CTEPH-patients, 15 women, median age (quartiles) 62y (49;73), mPAP 35 mmHg (31;44), PaO2 7.1 kPa (6.8;9.3) and 16 controls, 12 women, 60y (52;69), mPAP 18 mmHg (16;18), PaO2 9.5 kPa (8.5;10.6) were included. Hypoxia reduced the PaO2 in PAH/CTEPH-patients by median of 2.3 kPa, in controls by 3.3 kPa, difference (95%CI) in change 1.0 (0.02 to 1.9), p < 0.05. Corresponding changes in pulmonary vascular resistance, mPAP and cardiac output were nonsignificant in both groups. Hyperoxia decreased mPAP in PAH/CTEPH-patients by 4 mmHg (2 to 6), in controls by 2 mmHg (0 to 3), difference in change 3 mmHg (0 to 5), p < 0.05. CONCLUSIONS: In patients with PAH/CTEPH, very short-term exposure to moderate hypoxia similar to 2600 m altitude or during commercial air travel did not deteriorate hemodynamics. These results encourage studying the response of PAH/CTEPH during daytrips to the mountain or air travel.

Shoshin beriberi-thiamine responsive pulmonary hypertension in exclusively breastfed infants: A study from northern India.

OBJECTIVE: To study the effect of thiamine administration on the resolution of pulmonary hypertension in exclusively breastfed infants. DESIGN: Prospective cohort study. SETTING: Hospital based study of a tertiary care hospital. PATIENTS: A total of 29 infants with 17 males (58.6%) and 12 females (41.4%) were included in the study. INTERVENTION: In addition to the management of shock, right heart failure and renal failure, patients received intravenous thiamine 100mg/kg IV followed by 10mg/day till introduction of supplementary feeds. MAIN OUTCOMES MEASURES: Resolution of shock, metabolic complications and pulmonary hypertension. RESULTS: Mean age at presentation was 78.45±30.7 days. All infants were exclusively breastfed. 86.2% of mothers were on customary dietary restrictions. Biventricular failure and tachycardia was commonly present. There were four deaths in our series. Acute metabolic acidosis was a universal feature with a mean pH of 7.21±0.15. Pulmonary hypertension was present in all patients on admission. Intravenous thiamine 100mg/kg IV stat was given immediately after documenting pulmonary hypertension. Repeat echocardiography showed complete resolution of pulmonary hypertension. CONCLUSION: Many infants present to us with Shoshin beriberi with unusually high pulmonary pressures. These patients respond to thiamine challenge with prompt resolution of metabolic complications and reversal of pulmonary hypertension. We believe this is first of its kind from the region, which is reported.

Chronic thromboembolic pulmonary hypertension (CTEPH) - potential role of multidetector-row CT (MD-CT) and MR imaging in the diagnosis and differential diagnosis of the disease.

Chronic thromboembolic pulmonary hypertension (CTEPH) can be defined as pulmonary hypertension (resting mean pulmonary arterial pressure of 25 mm Hg or more determined at right heart catheterization) with persistent pulmonary perfusion defects. It is a rare, but underdiagnosed disease with estimated incidences ranging from 0.5% to 3.8% of patients after an acute pulmonary embolism (PE), and in up to 10% of those with a history of recurrent PE. CTEPH is the only form of pulmonary hypertension that can be surgically treated leading to normalization of pulmonary hemodynamics and exercise capacity in the vast majority of patients. The challenges for imaging in patients with suspected CTEPH are fourfold: the imaging modality should have a high diagnostic accuracy with regard to the presence of CTEPH and allow for differential diagnosis. It should enable detection of patients suitable for PEA with great certainty, and allow for quantification of PH by measuring pulmonary hemodynamics (mPAP and PVR), and finally, it can be used for therapy monitoring. This overview tries to elucidate the potential role of ECG-gated multidetector CT pulmonary angiography (MD-CTPA) and MR imaging, and summarizes the most important results that have been achieved so far. Generally speaking, ECG-gated MD-CTPA is superior to MR in the assessment of parenchymal and vascular pathologies of the lung, and allows for the assessment of cardiac structures. The implementation of iodine maps as a surrogate for lung perfusion enables functional assessment of lung perfusion by CT. MR imaging is the reference standard for the assessment of right heart function and lung perfusion, the latter delineating typical wedge-shaped perfusion defects in patients with CTEPH. New developments show that with MR techniques, an estimation of hemodynamic parameters like mean pulmonary arterial pressure and pulmonary vascular resistance will be possible. CT and MR imaging should be considered as complementary investigations providing comprehensive information in patients with CTEPH.

Leg heating using far infra-red radiation in patients with chronic heart failure acutely improves the hemodynamics, vascular endothelial function, and oxidative stress.

BACKGROUND: Systemic thermal therapy (STT) has been associated with beneficial effects in patients with chronic heart failure (CHF). The fact, however, that it requires a dedicated as well as spacious facility and trained personnel makes it difficult to practice in the daily care of patients with CHF. OBJECTIVE: The aim of this study was to determine whether the leg thermal therapy (LTT) has a positive impact similar to that of STT in patients with CHF. Methods and Results Twenty patients with CHF (57 ± 17 years old, left ventricular ejection fraction=30 ± 10%) received LTT (45°C) for 20 minutes. Immediately after the treatment, the core temperature had increased (+0.3 ± 0.3°C) (p<0.01). While the LTT had no significant effects on the heart rate, systolic arterial pressure, and diastolic blood pressure, it increased the cardiac output (mixed venous oxygen saturation; +2 ± 3%) and decrease the pulmonary capillary wedge pressure (-2 ± 2 mmHg). The LTT significantly improved the flow-mediated vasodilatation (FMD) from 4.8 ± 2.6 to 7.1 ± 3.6%, the antioxidative markers, thiol from 4.0 ± 0.7 to 4.5 ± 0.9 µmoL/g, and the marker of oxidative deoxyribonucleic acid (DNA) damage, urine 8-hydroxy-2'deoxyguanosine (8OHdG) from 100 to 82 ± 3%, respectively (p<0.05). No patient had any adverse effects associated with LTT. Conclusion LTT acutely improved FMD, and oxidative stress in patients with CHF. Although the long-term effect of LTT remains to be investigated, its practicality which is comparable to that of STT would make it an attractive therapeutic strategy for patients with CHF.

The effects of stimulation at acupoint ST36 points against hemorrhagic shock in dogs.

The aim of this study is to investigate the effects of electroacupuncturing (EA) zusanli points on levels of basic hemodynamics, lactate, and cytokines in dogs with hemorrhagic shock. Thirty healthy dogs were randomly divided into 5 groups: sham hemorrhagic shocked group, hemorrhagic shocked group, EA group, nonacupuncturing group, and EA after vagotomy group. Zusanli points were electroacupunctured with constant voltage (10-15 V, 30 Hz) for 30 minutes immediately after the shock models were established. Before the stimulation, a blood pressure transducer was implanted into the right femoral artery for continuous recording of mean arterial pressure (MAP), and a 5F Swan-Ganz pediatric catheter was implanted into the pulmonary artery. The levels of serum tumor necrosis factor α (TNF-α) in the femoral artery were detected at 0, 120, and 180 minutes after hemorrhage. The levels of serum lactate in the femoral artery were detected before hemorrhage (-45 minutes), at 0 minute, and at 180 minutes. In the hemorrhagic shocked group, the levels of MAP, cardiac output, cardiac index, central venous pressure, and pulmonary arterial wedge pressure decreased significantly; at the same time, the levels of serum TNF-α and serum lactate increased significantly. There were no differences between these groups and the hemorrhagic group, but they were different from the sham hemorrhagic shocked group. In the EA group, the levels of MAP, cardiac output, cardiac index, central venous pressure, and pulmonary arterial wedge pressure gradually increased, but the content of serum TNF-α and lactate obviously decreased. The results suggested that EA zusanli points produce a protective effect on hemorrhagic shock in dogs.

Effects of a selective iNOS inhibitor versus norepinephrine in the treatment of septic shock.

Inhibition of NOS is not beneficial in septic shock; selective inhibition of the inducible form (iNOS) may represent a better option. We compared the effects of the selective iNOS inhibitor BYK191023 with those of norepinephrine (NE) in a sheep model of septic shock. Twenty-four anesthetized, mechanically ventilated ewes received 1.5 g/kg body weight of feces into the abdominal cavity to induce sepsis. Animals were randomized into three groups (each n = 8): NE-only, BYK-only, and NE + BYK. The sublingual microcirculation was evaluated with sidestream dark-field videomicroscopy. MAP was higher in the NE + BYK group than in the other groups, but there were no significant differences in cardiac index or systemic vascular resistance. Mean pulmonary arterial pressure was lower in BYK-treated animals than in the NE-only group. PaO2/FiO2 was higher and lactate concentration lower in the BYK groups than in the NE-only group. Mesenteric blood flow was higher in BYK groups than in the NE-only group. Renal blood flow was higher in the NE + BYK group than in the other groups. Functional capillary density and proportion of perfused vessels were higher in the BYK groups than in the NE-only group 18 h after induction of peritonitis. Survival times were similar in the three groups. In this model of peritonitis, selective iNOS inhibition had more beneficial effects than NE on pulmonary artery pressures, gas exchange, mesenteric blood flow, microcirculation, and lactate concentration. Combination of this selective iNOS inhibitor with NE allowed a higher arterial pressure and renal blood flow to be maintained.

Cinaciguat (BAY 58-2667) improves cardiopulmonary hemodynamics in patients with acute decompensated heart failure.

BACKGROUND: Cinaciguat (BAY 58-2667) is the first of a new class of soluble guanylate cyclase activators in clinical development for acute decompensated heart failure. We aimed to assess the hemodynamic effects, safety, and tolerability of intravenous cinaciguat in patients with acute decompensated heart failure (pulmonary capillary wedge pressure > or =18 mm Hg). METHODS AND RESULTS: After initial dose finding (part A; n=27), cinaciguat was evaluated in the nonrandomized, uncontrolled proof-of-concept part of the study (part B; n=33) using a starting dose of 100 microg/h, which could be titrated depending on hemodynamic response. Patients were categorized as responders if their pulmonary capillary wedge pressure decreased by > or =4 mm Hg compared with baseline. Final doses of cinaciguat after 6 hours of infusion in part B were 50 microg/h (n=2), 200 microg/h (n=12), and 400 microg/h (n=16). Compared with baseline, a 6-hour infusion of cinaciguat led to significant reductions in pulmonary capillary wedge pressure (-7.9 mm Hg), mean right atrial pressure (-2.9 mm Hg), mean pulmonary artery pressure (-6.5 mm Hg), pulmonary vascular resistance (-43.4 dynes . s . cm(-5)), and systemic vascular resistance (-597 dynes . s . cm(-5)), while increasing heart rate by 4.4 bpm and cardiac output by 1.68 L/min. The responder rate was 53% after 2 hours, 83% after 4 hours, and 90% after 6 hours. Cinaciguat was well tolerated, with 13 of 60 patients reporting 14 drug-related treatment-emergent adverse events of mild to moderate intensity, most commonly hypotension. CONCLUSIONS: Cinaciguat has potent preload- and afterload-reducing effects, increasing cardiac output. Further investigation of cinaciguat for acute decompensated heart failure is warranted.

[Clinical efficiency of ivabradine in patients with cardiorespiratory pathology].

Clinical efficiency of If-inhibitor ivabradin (Coraxan, Servier) in 40 patients with cardiorespiratory pathology (CRP) was studied. It was shown, that use of ivabradin in dose of 5 mg two times a day leaded to significant decrease in number of angina attacks in a week, and also in time of painless myocardial ischemia, decrease in heart rate at a day and during physical exercises, increase in 6 minutes walking distance and circadian index, oxygen saturation and partial tension, decrease in average pressure in pulmonary artery, increase in ejection fraction of left ventricle. Thus, ivabradin (Coraxan, Servier) is an effective antianginal drug for CRP patients, it improves life quality and do not has an influence on external respiration function. Ivabradin in dose of 5 mg two times a day can be used for CRP patients and as alternative to beta-adrenoblockers.

Hypothalamic injury as a cause of refractory hypotension after sellar region tumor surgery.

INTRODUCTION: Fluid-resistant arterial hypotension can result in hypoperfusion of the brain and other organs. Well-known causes of arterial hypotension in neurosurgical practice include cardiac failure, septic shock, adrenal insufficiency, brainstem, and cervical spinal cord damage. Fluid-resistant arterial hypotension can occur in patients with brain edema without damage to brainstem when hypothalamic nuclei suffer. This phenomenon is not a well-documented cause of hypotension. METHODS: We prospectively investigated 15 cases with clinical syndrome of arterial hypotension in patients following surgery for sellar region tumors. These cases were taken from 1005 patients operated between May 2003 and December 2005. Pulmonary artery catheter was used to investigate hemodynamic profile. RESULTS: The mechanism of arterial hypotension consisted of decrease of vascular tone (SVRI was 1503 +/- 624 dyn x s x cm(5) x m(2)) and relative hypovolemia (CVP: 4.5 +/- 2.6 torr, PAWP: 7.4 +/- 3.5 torr). In all cases arterial hypotension was corrected with phenylephrine after failure to respond to fluid resuscitation alone. Fluid balance was positive over the next 72 h. Twenty-seven percent of patients had transitory thyroid insufficiency. In these situations dopamine was administrated as symptomatic therapy and dose of thyroid hormone was increased. Mortality was 53%. CONCLUSION: Hypothalamic damage can result in life-threatening vasodilatory arterial hypotension after sellar region tumor surgery. beta-Sympatomimetics are indicated in cases with thyroid insufficiency.

The effect of electrical neurostimulation on collateral perfusion during acute coronary occlusion.

BACKGROUND: Electrical neurostimulation can be used to treat patients with refractory angina, it reduces angina and ischemia. Previous data have suggested that electrical neurostimulation may alleviate myocardial ischaemia through increased collateral perfusion. We investigated the effect of electrical neurostimulation on functional collateral perfusion, assessed by distal coronary pressure measurement during acute coronary occlusion. We sought to study the effect of electrical neurostimulation on collateral perfusion. METHODS: Sixty patients with stable angina and significant coronary artery disease planned for elective percutaneous coronary intervention were split in two groups. In all patients two balloon inflations of 60 seconds were performed, the first for balloon dilatation of the lesion (first episode), the second for stent delivery (second episode). The Pw/Pa ratio (wedge pressure/aortic pressure) was measured during both ischaemic episodes. Group 1 received 5 minutes of active neurostimulation before plus 1 minute during the first episode, group 2 received 5 minutes of active neurostimulation before plus 1 minute during the second episode. RESULTS: In group 1 the Pw/Pa ratio decreased by 10 +/- 22% from 0.20 +/- 0.09 to 0.19 +/- 0.09 (p = 0.004) when electrical neurostimulation was deactivated. In group 2 the Pw/Pa ratio increased by 9 +/- 15% from 0.22 +/- 0.09 to 0.24 +/- 0.10 (p = 0.001) when electrical neurostimulation was activated. CONCLUSION: Electrical neurostimulation induces a significant improvement in the Pw/Pa ratio during acute coronary occlusion.

Acute amlodipine overdose treated by high dose intravenous calcium in a patient with severe renal insufficiency.

Calcium salts are frequently used in the treatment of calcium antagonist poisoning. Different dosing regimens have been employed. The major risk of high dose calcium therapy is iatrogenic hypercalcemia, especially in patients with diminished renal function. Repeated doses of calcium are therefore often avoided; however, inadequate use of intravenous calcium may cause treatment failure in severe calcium antagonist overdose. We report our experience of using high dose intravenous calcium chloride effectively and safely to treat severe amlodipine overdose in a patient with severe renal insufficiency.

Nitric oxide up-regulates the glucocorticoid receptor and blunts the inflammatory reaction in porcine endotoxin sepsis.

OBJECTIVES: Nitric oxide inhibits the expression of many genes involved in inflammatory diseases. Glucocorticoids inhibit similar transcription factors. We hypothesized that there may be an interaction between nitric oxide and glucocorticoids, with the potential to enhance the anti-inflammatory effect when administered simultaneously. DESIGN: Prospective, randomized, controlled study. SETTING: Animal research laboratory. SUBJECTS: A total of 45 anesthetized and mechanically ventilated pigs. INTERVENTIONS: Lung and systemic injury was induced by intravenous infusion of endotoxin (lipopolysaccharide) for 6 hrs. After 2.5 hrs, one group received 3.5 mg/kg hydrocortisone, another group inhaled nitric oxide (30 ppm), and still another group received both steroid and nitric oxide. Control groups of healthy and endotoxin-exposed piglets were also studied. MEASUREMENTS AND MAIN RESULTS: Central hemodynamics and gas exchange were measured. Detection of the glucocorticoid receptor and inflammatory markers in lung, liver, and kidney tissue were made by immunohistochemistry, and morphology was studied with light microscopy. Endotoxin infusion markedly reduced glucocorticoid receptor expression in lung, liver, and kidney and up-regulated activator protein-1 and the inflammatory markers nuclear factor-kappaB and tumor necrosis factor-alpha. When administered separately, steroids and nitric oxide had modest effect on the inflammatory response. However, nitric oxide up-regulated the glucocorticoid receptor expression. Simultaneous administration of steroids and nitric oxide attenuated the inflammatory response and almost preserved or restored normal histology of both lung and systemic organs. When the glucocorticoid receptor was blocked by a receptor antagonist (mifepristone, 600 mg) and inhaled nitric oxide was subsequently administered, no increase in the expression of the glucocorticoid receptor was seen. CONCLUSION: We suggest that up-regulation of glucocorticoid receptor expression by nitric oxide made steroid therapy more effective.

Protective effects of atorvastatin in rat models of acute pulmonary embolism: involvement of matrix metalloproteinase-9.

OBJECTIVE: Matrix metalloproteinases (MMPs) have been implicated in the pathophysiology of acute pulmonary embolism (APE)-induced pulmonary hypertension. Here, we evaluate the effects of atorvastatin pretreatment on APE-induced pulmonary hypertension, 24-hr mortality rate, and changes in plasma and lung MMP-2 and MMP-9 activities. DESIGN: Controlled animal study. SETTING: University research laboratory. SUBJECTS: Male Wistar rats. INTERVENTIONS: Rats received atorvastatin (30 mg/kg/day orally) or tap water for 2 wks. In study 1, we examined whether atorvastatin affected APE-induced pulmonary hypertension by using a rat isolated lung perfusion model of APE. In study 2, we examined whether atorvastatin affects the survival rate after APE, which was induced by rapid intravenous injection of 14 mg/kg of a suspension of microspheres (or saline) into the tail vein. MEASUREMENTS AND MAIN RESULTS: Plasma nitrite/nitrate concentrations were measured by chemiluminescence. Pretreatment with atorvastatin was associated with 49% higher nitrite/nitrate levels compared with controls (p < .05). In study 1, whereas APE increased mean pulmonary artery pressure (MPAP) by 13.0 +/- 1.6 mm Hg in perfused lungs isolated from rats pretreated with water, pretreatment with atorvastatin attenuated by 27% the increases in MPAP after APE. In study 2, pretreatment with atorvastatin was associated with a significant increase in 24-hr survival rate after APE, which was 48% in embolized rats pretreated with water and 64% in rats pretreated with atorvastatin (p < .05). Gelatin zymography of lung and plasma MMP-2 and MMP-9 was performed. Lungs and plasma from embolized rats showed higher levels of both pro- and activated forms of MMP-9 compared with those from nonembolized animals (all p < .05). However, pretreatment with atorvastatin attenuated by 32% the increases in lung-activated MMP-9 levels after APE (p < .05). CONCLUSIONS: These results suggest that pretreatment with atorvastatin attenuates APE-induced pulmonary hypertension and increases 24-hr survival rate by mechanisms that result in attenuated increases in lung activated MMP-9 after APE.

Vitamin E attenuates acute lung injury in sheep with burn and smoke inhalation injury.

INTRODUCTION: A decrease in alpha-tocopherol (vitamin E) plasma levels in burn patients is typically associated with increased mortality. We hypothesized that vitamin E supplementation (alpha-tocopherol) would attenuate acute lung injury induced by burn and smoke inhalation injury. MATERIALS AND METHODS: Under deep anesthesia, sheep (33 +/- 5 kg) were subjected to a flame burn (40% total body surface area, third degree) and inhalation injury (48 breaths of cotton smoke, < 40 degrees C). Half of the injured group received alpha-tocopherol (1000 IU vitamin E) orally, 24 h prior to injury. The sham group was neither injured nor given vitamin E. All three groups (n = 5 per group) were resuscitated with Ringer's lactate solution (4 ml/kg/%burn/24 h), and placed on a ventilator (PEEP = 5 cmH2O; tidal volume = 15 ml/kg) for 48 h. RESULTS: Plasma alpha-tocopherol per lipids doubled in the vitamin E treated sheep. Vitamin E treatment prior to injury largely prevented the increase in pulmonary permeability index and moderated the increase in lung lymph flow (52.6 +/- 6.2 ml/min, compared with 27.3 +/- 6.0 ml/min, respectively), increased the PaO2/FiO2 ratio, ameliorated both peak and pause airway pressure increases, and decreased plasma conjugated dienes and nitrotyrosine. CONCLUSIONS: Pretreatment with vitamin E ameliorated the acute lung injury caused by burn and smoke inhalation exposure.

Goal-directed therapy of cardiac preload in induced whole-body hyperthermia.

OBJECTIVES: To optimize volume therapy during induced whole-body hyperthermia (WBH) < or = 42.2 degrees C, pulmonary capillary wedge pressure (PCWP) and intrathoracic blood volume index (ITBVI) were compared as goal parameters. DESIGN: Prospective clinical study. SETTING: ICU at university hospital. PATIENTS: Twenty-three patients with metastatic cancers. INTERVENTIONS: Radiant WBH in combination with induced hyperglycemia, hyperoxemia, and chemotherapy was applied. Volume therapy was directed to the PCWP (group A, 8 to 12 mm Hg [20 treatments]), or to ITBVI (group B, 800 to 1,100 mL/m2 [19 treatments]) following a standardized protocol. Goals other than PCWP and ITBVI were cardiac index of > 3.5 L/min/m2 and mean arterial pressure of > 55 mm Hg. MEASUREMENTS AND RESULTS: In addition to the primary goals PCWP and ITBVI, at defined temperatures, central venous pressure (CVP), extravascular lung water index, the number of infusions, and packed RBCs, as well as serum lactate level, norepinephrine dosage, and levels of liver enzymes, bilirubin, creatinine, and urea were measured. Patients in group A received a significantly greater mean (+/- SD) amount of crystalloids compared to those in group B (6,175 +/- 656 vs 3,947 +/- 375 mL, respectively) and required significantly lower dosages of vasoconstrictors compared with patients in group B. Except for the lower values of CVP in patients in group A during hyperthermia, all of the other hemodynamic and laboratory parameters showed no significant differences between the groups or stayed in a normal range. CONCLUSION: PCWP and ITBVI are useful parameters to assess preload in induced WBH. Differences in crystalloids and vasopressor dosages may suggest an appropriate ITBVI of > 1,100 mL/m2 for patients with good cardiopulmonary health under such extremely hypercirculatory conditions.

Cerebral perfusion pressure elevation with oxygen-carrying pressor after traumatic brain injury and hypotension in Swine.

BACKGROUND: Previously, we had shown that elevation of cerebral perfusion pressure, using pressors, improved short-term outcomes after traumatic brain injury and hemorrhagic shock in swine. The current study evaluates outcomes after resuscitation with diaspirin cross-linked hemoglobin (DCLHb)--a hemoglobin-based oxygen carrier with pressor activity--in the same swine model of traumatic brain injury and hemorrhagic shock. METHODS: Anesthetized and ventilated swine received traumatic brain injury via cortical fluid percussion (6-8 atm) followed by 45% blood volume hemorrhage. One hour later, animals were randomized to either a control group (SAL) resuscitated with normal saline equal to three times shed blood volume or to one of two experimental groups resuscitated with DCLHb. The two experimental groups consisted of a low-dose group, resuscitated with 250 mL of DCLHb (Hb1), and a high-dose group, resuscitated with 500 mL of DCLHb (Hb2). Animals were observed for 210 minutes postresuscitation. Outcomes evaluated were cerebral oxygenation by measuring partial pressure and saturation of oxygen in cerebrovenous blood; cerebral function by evaluating the preservation and magnitude of cerebrovascular carbon dioxide reactivity; and brain structural damage by semiquantitatively assessing beta amyloid precursor protein positive axons. RESULTS: Postresuscitation, cerebral perfusion pressure was higher in the DCLHb groups (p < 0.05, Hb1 and Hb2 vs. SAL), and intracranial pressure was lower in the Hb2 group (p < 0.05 vs. SAL). Cerebrovenous oxygen level was similar in all groups (p > 0.05). At baseline, 5% carbon dioxide evoked a 16 +/- 1% increase in cerebrovenous oxygen saturation, indicating vasodilatation. At 210 minutes, this response was nearly absent in SAL (4 +/- 4%) (p < 0.05 vs. baseline) and Hb1 (1 +/- 5%), but was partially preserved in Hb2 (9 +/- 5%). There was no intergroup difference in beta amyloid precursor protein positive axons. Five of 20 SAL and 0 of 13 DCLHb animals developed brain death (flat electroencephalogram) (p = 0.05, SAL vs. DCLHb). Postresuscitation, DCLHb animals maintained higher mean pulmonary arterial pressure (28 +/- 1 mm Hg, SAL; 42 +/- 1 mm Hg, Hb1; 45 +/- 1 mm Hg, Hb2) (p < 0.05, Hb1 and Hb2 vs. SAL) and lower cardiac output (3.9 +/- 1.6 L/min, SAL; 2.6 +/- 0.1 L/min, Hb1; 2.7 +/- 0.1 L/min, Hb2) (p < 0.05, Hb1 and Hb2 vs. SAL). Three Hb2 animals died as a result of cardiac failure, and one SAL animal died as a result of irreversible shock. CONCLUSION: In this swine model of traumatic brain injury and hemorrhagic shock, resuscitation with DCLHb maintained a higher cerebral perfusion pressure. Low-dose DCLHb (minimal increase in oxygen carriage) failed to significantly improve short-term outcome. With high-dose DCLHb (significant improvement in oxygen carriage), intracranial pressure was lower and cerebrovascular carbon dioxide reactivity was partially preserved; however, this was at the cost of poorer cardiac performance secondary to high afterload.

Comparison of aerosol therapy with different perfluorocarbons in surfactant-depleted animals.

OBJECTIVE: The study investigates the effectiveness of aerosol treatment on gas exchange and pulmonary inflammatory reaction using perfluorocarbons with different molecular structure and vapor pressure. DESIGN: Experimental, prospective, randomized, controlled study. SETTING: Experimental laboratory at a university hospital. SUBJECTS: Twenty anesthetized neonatal piglets assigned to four groups. INTERVENTIONS: After establishment of lung injury by bronchoalveolar lavage, piglets either received aerosolized FC77 (n = 5), perfluorooctylbromide (n = 5), or FC43 (n = 5, 10 mL x kg(-1) x hr(-1) for 2 hrs) or intermittent mandatory ventilation (control, n = 5). Thereafter, animals were supported for another 6 hrs. MEASUREMENTS AND MAIN RESULTS: Pao2 significantly improved in the perfluorocarbon groups compared with control (p < .01). Final Pao2 (mean +/- SEM) was FC77, 406 +/- 27 mm Hg; perfluorooctylbromide, 332 +/- 32 mm Hg; FC43, 406 +/- 19 mm Hg; control, 68 +/- 8 mm Hg. Paco2 and mean pulmonary arterial pressure were lower in all perfluorocarbon groups compared with control. The ratio of terminal dynamic compliance to total compliance was significantly higher in the FC77 than in the FC43, perfluorooctylbromide, and control groups. Relative gene expression of interleukin-1beta, interleukin-8, P-selectin, E-selectin, and intercellular adhesion molecule-1 in lung tissue was determined by TaqMan real time polymerase chain reaction normalized to hypoxanthineguanine-phosphoribosyl-transferase and was shown to be reduced by all perfluorocarbons. CONCLUSIONS: Aerosol treatment with all the perfluorocarbons investigated improved gas exchange and reduced pulmonary inflammatory reaction independently from molecular structure and vapor pressure of the perfluorocarbons. Although differences in vapor pressure and molecular structure may account for varying optimal dosing strategies, several different perfluorocarbons were shown to be principally suitable for aerosol treatment.

Occurrence and management of atrial arrhythmia after long-term Fontan circulation.

OBJECTIVES: In patients after the Fontan operation, we determined risk factors for late failure and for intra-atrial re-entrant tachycardia at 15 to 20 years' follow-up. Midterm results after electrophysiologic ablation therapy for these tachycardias were also evaluated. METHODS: Current follow-up was available in 162 patients (2005 patient-years) with a wide range of underlying diagnoses operated on between February 1978 and May 1995. Risk factor analysis included patient-related and procedure-related variables, with late failure and the incidence of re-entrant tachycardia as outcome parameters. RESULTS: Forty late failures were observed (2.0 per 100 patient-years). At 15 years, Kaplan-Meier estimated survival was significantly (P =.007) better for patients with tricuspid atresia (93%) compared with that for patients with complex congenital malformation (71%). The sole multivariable risk factor for Fontan failure was the type of underlying diagnosis. At 20 years' follow-up, overall freedom from tachycardia was estimated to be 46% +/- 12%. Acute success of electrophysiologic ablation was seen in 25 (83%) of 30 patients, and Kaplan-Meier estimated freedom from recurrent tachycardia was 81% +/- 10% at 3 years. Multivariate analysis identified duration of Fontan circulation as the sole risk factor for re-entrant tachycardias. CONCLUSION: After the modified Fontan operation, long-term survival in patients with tricuspid atresia was significantly better compared with that in patients with complex congenital malformations. As first-choice therapy for atrial re-entrant tachycardias, we recommend electrophysiologic ablation therapy.