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R Bellomo

Publications and source records attributed to R Bellomo.

At least 127 records · Page 7Linked to original sources

Role of pump prime in the etiology and pathogenesis of cardiopulmonary bypass-associated acidosis.

BACKGROUND: The development of metabolic acidosis during cardiopulmonary bypass (CPB) is well recognized but poorly understood. The authors hypothesized that the delivery of pump prime fluids is primarily responsible for its development. Accordingly, acid-base changes induced by the establishment of CPB were studied using two types of priming fluid (Haemaccel, a polygeline solution, and Ringer's Injection vs. Plasmalyte 148) using quantitative biophysical methods. METHODS: A prospective, double-blind, randomized trial was conducted at a tertiary institution with 22 patients undergoing CPB for coronary artery bypass surgery. Sampling of arterial blood was performed at three time intervals: before CPB (t1), 2 min after initiation of CPB at full flows (t2), and at the end of the case (t3). Measurements of Na+, K+, Mg2+, Cl-, HCO3-, phosphate, Ca2+, albumin, lactate, and arterial blood gases at each collection point were performed. Results were analyzed in a quantitative manner. RESULTS: Immediately on delivery of pump prime fluids, all patients developed a metabolic acidosis (base excess: 0. 95 mEq/l (t1) to -3.65 mEq/l (t2) (P < 0.001) for Haemaccel-Ringer's and 1.17 mEq/l (t1) to -3.20 mEq/l (t2). The decrease in base excess was the same for both primes (-4.60 vs. -4.37; not significant). However, the mechanism of metabolic acidosis was different. With the Haemaccel-Ringer's prime, the metabolic acidosis was hyperchloremic (Delta Cl-, +9.50 mEq/l; confidence interval, 7.00-11.50). With Plasmalyte 148, the acidosis was induced by an increase in unmeasured anions, most probably acetate and gluconate. The resolution of these two processes was different because the excretion of chloride was slower than that of the unmeasured anions (Delta base excess from t1 to t3 = -1.60 for Haemaccel-Ringer's vs. +1.15 for Plasmalyte 148; P = 0.0062). CONCLUSIONS: Cardiopulmonary bypass-induced metabolic acidosis appears to be iatrogenic in nature and derived from the effect of pump prime fluid on acid-base balance. The extent of such acidosis and its duration varies according to the type of pump prime.

Acid-Base Equilibrium↗

The effect of intensive plasma water exchange by hemofiltration on hemodynamics and soluble mediators in canine endotoxemia.

High volume hemofiltration (HVHF) (200 ml/kg/h) improves hemodynamics in experimental septic shock but is difficult to apply clinically. Accordingly, we studied whether less intensive HVHF (80 ml/kg/h) can still improve hemodynamics in experimental septic shock. We also investigated its effect on the serum concentrations of several inflammatory mediators, including endothelin (ET-1), endotoxin (LPS), tumor necrosis factor-alpha (TNF-alpha), and 6-keto prostaglandin F(1alpha) (6-kepto PGF(1alpha)). Sixteen anesthetized dogs were connected to a continuous veno-venous hemofiltration (CVVH) (filtration: 80 ml/kg/h) or sham circuit and endotoxin (0.5 mg/kg) was infused intravenously over 5 min. Hemodynamic variables were measured at baseline and at 15, 45, 90, and 180 min. The major hemodynamic finding was that endotoxin-induced hypotension was significantly attenuated by intensive CVVH (p < 0.04). Changes in cardiac output and right ventricular ejection fraction were equal in both groups. ET-1 levels, but not LPS, TNF-alpha, or 6-keto PGF(1alpha), were lower during CVVH (p = 0.042). Endotoxin or TNF-alpha were not found in the ultrafiltrate. Median clearances of ET-1 and 6-keto PGF(1alpha) during intensive CVVH were 8.8 and 25.9 ml/m, respectively. We conclude that intensive CVVH attenuates the early component of endotoxin-induced hypotension and reduces serum concentrations of endothelin-1. The effect of CVVH on blood pressure is not explained by convective clearance of the mediators in question.

6-Ketoprostaglandin F1 alpha↗

A prospective, multicenter study of the epidemiology, management, and outcome of severe acute renal failure in a "closed" ICU system.

The safety and effectiveness of "closed" intensive care units (ICUs) are highly controversial. The epidemiology and outcome of acute renal failure (ARF) requiring replacement therapy (severe ARF) within a "closed" ICU system are unknown. Accordingly, we performed a prospective 3-mo multicenter observational study of all Nephrology Units and ICUs in the State of Victoria (all "closed" ICUs), Australia, and focused on the epidemiology, treatment, and outcome of patients with severe ARF. We collected demographic, clinical, and outcome data using standardized case report forms. Nineteen ward patients and 116 adult ICU patients had severe ARF (13.4 cases/100, 000 adults/yr). Among the ICU patients with severe ARF, 37 had impaired baseline renal function, 91 needed ventilation, and 95 needed vasoactive drugs. Intensivists controlled patient care in all cases. Continuous renal replacement therapy (CRRT) was used in 111 of the ICU patients. Nephrological opinion was sought in only 30 cases. Predicted mortality was 59.6%. Actual mortality was 49.2%. Only 11 ICU survivors were dialysis dependent at hospital discharge. In the state of Victoria, Australia, intensivists manage severe ARF within a "closed" ICU system. Renal replacement is typically continuous and outcomes compare favorably with those predicted by illness severity scores. Our findings support the safety and efficacy of a "closed" ICU model of care.

Acute Kidney Injury↗

Postoperative fibrinolysis diagnosed by thrombelastography.

Thrombelastography is a useful method for the monitoring of bedside coagulation, especially for fibrinolysis. We report a case where thrombelastography facilitated early detection of fibrinolysis with significant clinical bleeding in a patient immediately following hip replacement surgery. The early diagnosis enabled institution of antifibrinolytic therapy and monitoring of the patient's response. It is likely to have led to less blood product transfusion and may possibly have prevented unnecessary surgical re-exploration.

Aged↗

The effect of PVC packaging on the acidity of 0.9% saline.

Intravenous fluids in polyvinyl chloride (PVC) packaging are known to be acidic. We proposed to determine the effect of PVC packaging on the pH of 0.9% saline solutions by comparing the predicted and measured pH of 0.9% saline equilibrated with atmospheric carbon dioxide and the measured pH of commercial solutions of 0.9% saline in PVC and polypropylene packaging. Calculation of pH was made from available physical chemistry constants and data. Measurement was made of the pH of 12 samples of prepared 0.9% saline equilibrated with atmospheric carbon dioxide. Comparison with the pH of seven commercial samples of saline in PVC packaging for intravenous use was undertaken. Further comparison was made between commercial samples of 0.9% saline in PVC or polypropylene packaging. The calculated pH of 0.9% saline was 5.61 at 20 degrees C. The median pH of the prepared samples was statistically significantly less acidic than the median pH of the PVC packaged samples for intravenous use: 5.47 vs 4.60, P < 0.05. The median pH of the PVC packaged saline was also statistically significantly more acidic than the pH of the polypropylene packaged saline: 4.62 vs 5.71, P < 0.05. The acidity of the intravenous solutions of 0.9% saline packaged in PVC was much greater than expected and is only partially explained by dissolved carbon dioxide. This acidity could be a result of packaging in PVC.

Acids↗

Prediction of the mediastinal drainage after coronary artery bypass surgery.

Using multiple correlation and linear regression approaches, we investigated the association between the amount of mediastinal drainage for the first 24 postoperative hours and clinical variables as well as multiple haematological tests performed at three time points: before anaesthesia induction, 10 minutes after protamine administration and just after skin closure, on 46 patients undergoing primary coronary artery bypass grafting. Three models from the three times were then developed to predict mediastinal drainage. The number of internal mammary grafts, the total number of grafts and plasma fibrinogen concentration were useful predictors of mediastinal drainage at all three times. The platelet count taken only after skin closure was found to provide additional predictive information. Each regression model explained approximately 60% of the variation in postoperative mediastinal drainage. The information obtained from these predictive models is useful in defining high-risk populations.

Aged↗

The epidemiology of major early adverse physiological events after surgery.

OBJECTIVE: To study the incidence of major post-operative adverse physiological events in a tertiary hospital. METHODS: Non-cardiac, surgical in-patients were studied for the first three post-operative days. Daily assessment was by patient visit, chart review and laboratory result analysis. Pre-determined diagnostic criteria for the identification of adverse physiological events were used. RESULTS: One hundred and seven patients were studied. The mean age was 61 +/- 20 years. Forty-four were female and 63 were male. Pre-operatively, 48 patients had one or more of 34 different co-morbidities. Forty three (40%) of the 107 patients had one or more major adverse physiological events. These events included hypotension 24 (22%), altered mental state 16 (15%), oliguria 9 (8.4%), abnormal heart rate 8 (7.5%) and abnormal respiratory rate 5 (4.7%). Morbidity associated with these events included respiratory failure 5 (4.7%), prolonged altered mental state 5, (4.7%), and septic shock 3 (2.8%). There were two deaths. Adverse physiological events were common in thoracic 5/9 (56%), neurosurgical 4/10 (40%) and vascular 8/13 (62%) patients. Prolonged altered mental state was most common among orthopaedic patients 5/22 (23%). Adverse physiological events were more frequent in the elderly than the young: 14/52 (27%) in those who were less than 65 years of age versus 29/55 (53%) in those who were 65 years and older (p < 0.025). There was a non-significant increase (p < 0.1) in adverse physiological events in patients having emergency surgery 16/28 (57%) compared with those having elective surgery 27/79 (34%). CONCLUSIONS: This study reveals a high incidence of post-operative adverse physiological events in surgical patients in a university teaching hospital and identifies several high-risk groups. Further studies are needed to define the clinical significance of these events, appropriate management and prognosis.

Journal Article↗

Oxygen consumption and lactate release by the lung after cardiopulmonary bypass and during septic shock.

OBJECTIVE: We sought to determine whether a correlation exists between lung lactate release and lung oxygen consumption by studying adult intensive care patients, either after cardiopulmonary bypass (CPB) or with septic shock. METHODS: A prospective observational study of six post cardiopulmonary bypass patients and seven patients with septic shock was performed in an intensive care unit of a major teaching hospital. Pulmonary oxygen consumption was estimated by subtracting oxygen consumption calculated using the reverse Fick equation (V O2Fick) from that measured by indirect calorimetry (V O2meas). Pulmonary lactate release was derived from the difference between arterial and mixed-venous lactate, multiplied by cardiac output. RESULTS: Pulmonary oxygen consumption comprised a substantial component of total oxygen consumption (CPB-median: 20.6%; interquartile range (IQR): 15.4 - 27.3%; septic shock-median: 32.3%; IQR: -4.0 - 35.4%). Lung lactate release occurred both after CPB (median: 27.5 mmol/hr; IQR: 24.8-64.1 mmol/hr) and with septic shock (median: 55.4 mmol/hr; IQR: 24.3 - 217.6 mmol/hr). Although no correlation was found between lung lactate release and pulmonary oxygen consumption, lactate release correlated with V O2meas and V O2Fick in septic patients (p < 0.005). CONCLUSIONS: We conclude that lung oxygen consumption and lactate release are substantial in conditions associated with lung inflammation. Lactate release and lung oxygen consumption may not share a common pathogenesis, however there is an association between lung lactate release and systemic oxygen consumption in sepsis.

Journal Article↗

Transforming growth factor-beta-induced expression of CD94/NKG2A inhibitory receptors in human T lymphocytes.

Different HLA class I-specific killer inhibitory receptors (KIR) are expressed in vivo by a fraction of activated T cells, predominantly CD8+, in which they may inhibit TCR-mediated cell functions. In an attempt to identify mechanisms leading to KIR expression in T cells, we analyzed the effect of transforming growth factor-beta (TGF-beta) in T cells responding to bacterial superantigens in vitro. We show that TGF-beta induces the expression of CD94/NKG2A in cells responding to toxic shock syndrome toxin 1 or to other staphylococcal superantigens. Remarkably, maximal CD94 expression occurred at (low) TGF-beta concentrations which have no substantial effect on lymphocyte proliferation. Maximal CD94 expression occurred when TGF-beta was added shortly after the cells were placed in culture. No expression could be induced in CD94/NKG2A-negative T cell clones. Although both CD4+ and CD8+ expressed CD94, the simultaneous expression of NKG2A was mostly confined to CD8+ cells. Monoclonal antibody-mediated cross-linking of CD94/NKG2A led to an impairment of T cell triggering via CD3, as determined in a redirected killing assay using the Fcgamma receptor-positive P815 murine target cells.

Animals↗

The aetiology and pathogenesis of cardiopulmonary bypass-associated metabolic acidosis using polygeline pump prime.

OBJECTIVE: The pathogenesis of the metabolic acidosis of cardiopulmonary bypass (CPB) is not fully understood. New quantitative methods of acid-base balance now make it possible to describe it more clearly. Accordingly, we studied acid-base changes during CPB with polygeline pump prime and defined and quantified the factors which contribute to metabolic acidosis. DESIGN: Prospective cohort study. SETTING: Tertiary institution. PARTICIPANTS: 10 cardiac bypass graft surgery patients. INTERVENTIONS: Sampling of arterial blood at four time intervals: post-induction, on CPB during cooling and rewarming, and at skin closure. Measurement of serum Na+, K+, Mg++, Ca++, Cl-, bicarbonate, and phosphate concentrations, arterial blood gases, and serum albumin, lactate, and pyruvate concentrations at each collection point. Analysis of findings according to quantitative physicochemical principles, including calculation of the strong ion difference apparent, the strong ion difference effective, and the strong ion gap (SIG). MEASUREMENTS AND MAIN RESULTS: All patients developed a mild metabolic acidosis. The median serum standard bicarbonate concentration decreased from 25.0 mEq/l post-induction to 22.3 mEq/l at cooling and 22.2 mEq/l at rewarming (p < 0.05). The standard base excess decreased from a median of 1.55 mEq/l prior to CPB, to -2.50 mEq/l at cooling, -1.65 mEq/l at rewarming and, -0.85 mEq/l at skin closure (p < 0.001). This mild metabolic acidosis occurred despite a decrease in the median serum lactate concentration from 3.20 mEq/l post-induction to 1.83, 1.80, and 1.58 mEq/l at the three other time points. The increase in the median serum chloride concentration from 104.9 mEq/l post induction to 111.0, 111.1, and 110.0 mEq/l at the subsequent time points (p < 0.0001) was the main cause of the acidosis. There was also a significant increase in the SIG of 3.8 mEq/l at cooling and rewarming (p < 0.0001), suggesting a role for other unmeasured anions (polygeline) in the genesis of this acidosis. CONCLUSIONS: Using quantitative biophysical methods, it can be demonstrated that, in patients receiving a pump prime rich in chloride and polygeline, the metabolic acidosis of CPB is mostly due to iatrogenic increases in serum chloride concentration and unmeasured strong anions (SIG). Its development is partially attenuated by iatrogenic hypoalbuminaemia. Changes in lactate concentrations did not play a role in the development of metabolic acidosis in our patients.

Acid-Base Equilibrium↗

Nitric oxide metabolism in canine sepsis: relation to regional blood flow.

PURPOSE: To investigate the role of nitric oxide (NO) in early endotoxemia on the systemic and regional blood flow by measuring the plasma nitrite/nitrate (NOx) and blood nitrosyl-hemoglobin (NO-Hb) levels. MATERIALS AND METHODS: This was a prospective, controlled, experimental study conducted in an animal research laboratory on 15 male mongrel dogs. Escherichia coli endotoxin (1 mg/kg) was injected intravenously. RESULTS: Hepatic, renal, and iliac blood flow and cardiac output (CO) were measured before and 15, 30, 45, 90 and 180 minutes after injection of Escherichia coli endotoxin (1 mg/kg) (n = 6). NOx efflux from the organs was calculated by measuring plasma NOx levels. The arterial blood levels of NO-Hb were also measured (n = 4). As control studies, blood samples from dogs (n = 5) without exposure to endotoxin were assayed at 180 minutes for NOx and NO-Hb. Following endotoxin injection, mean arterial pressure decreased and reached its lowest value at 90 minutes (baseline vs. 90 minutes: 119.1+/-5.8 vs. 82.5+/-16.7 mm Hg, P<.0001). Hepatic artery blood flow increased significantly (baseline vs. 180 minutes: 23.6+/-12.0 vs. 170.0+/-68.4 mL/ min, P<.0001). There were no significant changes in plasma levels of NOx, uptake or release of NOx across the measured vascular beds, NO-Hb levels at any time point. In the portal system, the portal vein flow correlated with NOx release (R = 0.69, P<.0001). CONCLUSION: In the early phase of endotoxemia in the dog, the significant reduction in systemic vascular resistance and hepatic arterial resistance are not associated with any measurable NOx release in the systemic circulation or the liver.

Animals↗

Trace element and vitamin concentrations and losses in critically ill patients treated with continuous venovenous hemofiltration.

OBJECTIVES: To measure the blood concentrations of a number of trace elements and vitamins in critically ill patients and examine their elimination by continuous venovenous hemofiltration (CVVH). SETTING: Intensive care unit of a tertiary institution. DESIGN: Prospective, controlled, clinical study. PATIENTS: Eight critically ill patients requiring renal replacement therapy, nine patients requiring intensive care treatment but not requiring renal replacement therapy, and nine healthy controls. INTERVENTIONS: Measurement of trace element and vitamin concentrations in blood and ultrafiltrate. MEASUREMENTS AND MAIN RESULTS: Compared with normal volunteers, critically ill patients requiring CVVH had significantly lower median blood concentrations of vitamin C, vitamin E, selenium, and zinc. During the first 24 hrs of CVVH, there were no changes in the trace element and vitamin concentrations in blood, nor were there differences between pre- and postfilter samples. Micronutrient losses in the ultrafiltrate were small or undetectable except for Vitamin C, chromium, and copper. Compared with normal volunteers, critically ill patients not requiring CVVH also had significantly lower median blood concentrations of vitamin C, vitamin E, selenium, and zinc. There were no differences between the two critically ill groups. CONCLUSIONS: The clinical significance of the reductions in blood concentrations of selenium, zinc, vitamin C, and vitamin E in critically ill patients and the ultrafiltrate losses of Vitamin C, copper, and chromium remains unclear.

Ascorbic Acid Deficiency↗

Myocardial cell injury in septic shock.

OBJECTIVE: To determine the presence of otherwise undetected myocardial cell injury in patients with septic shock using daily measurements of cardiac troponin I (cTN I). DESIGN: Prospective observational study. SETTING: Intensive care unit of a tertiary institution. PATIENTS: Fifteen consecutive patients with septic shock and six mechanically ventilated patients without septic shock. INTERVENTIONS: Daily collection of blood for the measurement of cTN I serum levels. Regular biochemical and hemodynamic assessment. Illness severity assessment and collection of demographic data. MEASUREMENTS AND MAIN RESULTS: Fifteen patients were studied for a median period of 3 days (range, 1 to 9 days). Serum cTN I concentrations were elevated to values otherwise considered diagnostic of acute myocardial infarction in 12 patients and were significantly higher than in critically ill controls (p = .01). All three patients who died in the intensive care unit and all four patients who did not survive beyond 28 days had elevated levels of cTN I. Survivors tended to lower levels of cTN I while in septic shock than nonsurvivors, and all three patients without increased cTN I survived. There was a significant positive correlation between vasoactive drug requirements and cTN I level (p = .04) and a significant negative correlation between cTN I concentration and left ventricular stroke work index (p = .01). CONCLUSION: Myocardial cell injury appears to be common in patients with septic shock and correlates with cardiac dysfunction.

APACHE↗

Role of the splanchnic circulation in acid-base balance during cardiopulmonary bypass.

OBJECTIVE: The role of the splanchnic circulation in the development of the metabolic acidosis of cardiopulmonary bypass (CPB) is not fully understood. New quantitative methods of acid-base balance now offer the ability to define this phenomenon more accurately. Accordingly, we studied acid-base changes across the splanchnic circulation during CPB and defined and quantified the factors that contributed to acid-base balance. DESIGN: Prospective cohort study. SETTING: Tertiary institution. PATIENTS: Ten patients undergoing CPB for coronary artery bypass surgery. INTERVENTIONS: Sampling of arterial and hepatic venous blood at four time intervals: postinduction, on CPB during cooling and rewarming, and at skin closure. MEASUREMENTS: Measurement of serum Na+, K+, Mg++, Ca++, Cl-, HCO3-, and phosphate concentrations, arterial and hepatic venous blood gases and serum albumin, and lactate and pyruvate concentrations at each collection point. Analysis of findings according to quantitative physicochemical principles. MAIN RESULTS: All patients developed a mild metabolic acidosis with a decrease in median serum bicarbonate concentration from 24.97 mEq/L after induction to 22.29 mEq/L at cooling and 22.23 mEq/L at rewarming (p < .05). Before CPB, the pH decreased by 0.0275 (p < .05) across the splanchnic circulation, representing an increase of 2.26 nmol/L of hydrogen ions. Nevertheless, the splanchnic circulation induced a metabolic alkalosis, with a median transsplanchnic increase in the base excess of 1.50 mEq/L (p < .05). This change was largely due to a decrease in serum chloride and lactate concentration across the splanchnic circulation (p < .05). The acidifying effect of the splanchnic circulation was therefore the result of cell respiration with a median increase in carbon dioxide tension of 5.75 mm Hg (p < .05), causing the strong ion difference effective to increase by 1.94 mEq/L (p < .05). There were no other anions or acids added to the circulation by splanchnic organs (no change in strong ion gap). During and after CPB the splanchnic metabolic alkalinizing effect continued and the respiratory acidifying effect was reduced. This caused the splanchnic circulation to be pH neutral at these times. CONCLUSIONS: Using quantitative biophysical methods it can be demonstrated that the splanchnic circulation does not contribute to the metabolic acidosis of CPB, and that it continues to have a metabolic alkalinizing effect involving significant lactate extraction. However, its respiratory acidifying effect continues, although at a reduced rate.

Acid-Base Equilibrium↗

Metabolic changes in neuronal migration disorders: evaluation by combined MRI and proton MR spectroscopy.

PURPOSE: To assess the role of 1H-magnetic resonance spectroscopy (MRS) in detecting biochemical abnormalities in neuronal migration disorders (NMDs). METHODS: We performed 1H-MRS studies on 17 brain NMD areas [five polymicrogyria, eight subcortical heterotopia, and four cortical dysplasia on magnetic resonance imaging (MRI)]. The study group consisted of 15 patients, all but one affected by partial epileptic seizures. Spectra were acquired from volumes of interest localized on NMDs and contralateral sides and compared with those obtained on gray and white matter of 18 neurologic controls. RESULTS: NMD lesions were characterized by lower N-acetylaspartate to creatine (NAA/Cr) and choline to Cr (Cho/Cr) ratios than those of the white (p = 0.002 and p = 0.004) and gray matter (p = 0.03 and p = 0.06) of neurologic controls. In addition, the normal-appearing contralateral sides to the NMD lesions showed a significant decrease of Cho/Cr ratio when compared with those of white (p = 0.003) and gray matter (p = 0.05) of neurologic controls. No relation was found between NAA/Cr decrease, EEG abnormalities, and NMD sides, or between NAA/Cr ratios, duration of epilepsy, and frequency of seizures. Lactate signal was detected in the spectra of four patients who had an epileptic seizure a short time before MR examination. CONCLUSIONS: NAA/Cr decrease may be related more to structural and functional alteration of the NMD sides than to epileptic activity in these lesions. Low Cho/Cr may be related to a more extensive diffuse hypomyelination than suggested by the MRI findings. An activation of anerobic glycolysis during and after seizures could account for the presence of lactate. These data confirm that H-MRS is an advanced technique that may provide useful biochemical information in vivo on neurobiologic processes underlying NMDs.

Brain↗