Effects of cardiac preload reduction and dobutamine on hepatosplanchnic blood flow regulation in porcine endotoxemia.

Insufficient cardiac preload and impaired contractility are frequent in early sepsis. We explored the effects of acute cardiac preload reduction and dobutamine on hepatic arterial (Qha) and portal venous (Qpv) blood flows during endotoxin infusion. We hypothesized that the hepatic arterial buffer response (HABR) is absent during preload reduction and reduced by dobutamine. In anesthetized pigs, endotoxin or vehicle (n = 12, each) was randomly infused for 18 h. HABR was tested sequentially by constricting superior mesenteric artery (SMA) or inferior vena cava (IVC). Afterward, dobutamine at 2.5, 5.0, and 10.0 µg/kg per minute or another vehicle (n = 6, each) was randomly administered in endotoxemic and control animals, and SMA was constricted during each dose. Systemic (cardiac output, thermodilution) and carotid, splanchnic, and renal blood flows (ultrasound Doppler) and blood pressures were measured before and during administration of each dobutamine dose. HABR was expressed as hepatic arterial pressure/flow ratio. Compared with controls, 18 h of endotoxin infusion was associated with decreased mean arterial blood pressure [49 ± 11 mmHg vs. 58 ± 8 mmHg (mean ± SD); P = 0.034], decreased renal blood flow, metabolic acidosis, and impaired HABR during SMA constriction [0.32 (0.18-1.32) mmHg/ml vs. 0.22 (0.08-0.60) mmHg/ml; P = 0.043]. IVC constriction resulted in decreased Qpv in both groups; whereas Qha remained unchanged in controls, it decreased after 18 h of endotoxemia (P = 0.031; constriction-time-group interaction). One control and four endotoxemic animals died during the subsequent 6 h. The maximal increase of cardiac output during dobutamine infusion was 47% (22-134%) in controls vs. 53% (37-85%) in endotoxemic animals. The maximal Qpv increase was significant only in controls [24% (12-47%) of baseline (P = 0.043) vs. 17% (-7-32%) in endotoxemia (P = 0.109)]. Dobutamine influenced neither Qha nor HABR. Our data suggest that acute cardiac preload reduction is associated with preferential hepatic arterial perfusion initially but not after established endotoxemia. Dobutamine had no effect on the HABR.

Sedation and weaning from mechanical ventilation: effects of process optimization outside a clinical trial.

PURPOSE: We studied the effects of reorganization and changes in the care process, including use of protocols for sedation and weaning from mechanical ventilation, on the use of sedative and analgesic drugs and on length of respiratory support and stay in the intensive care unit (ICU). MATERIALS AND METHODS: Three cohorts of 100 mechanically ventilated ICU patients, admitted in 1999 (baseline), 2000 (implementation I, after a change in ICU organization and in diagnostic and therapeutic approaches), and 2001 (implementation II, after introduction of protocols for weaning from mechanical ventilation and sedation), were studied retrospectively. RESULTS: Simplified Acute Physiology Score II (SAPS II), diagnostic groups, and number of organ failures were similar in all groups. Data are reported as median (interquartile range). Time on mechanical ventilation decreased from 18 (7-41) (baseline) to 12 (7-27) hours (implementation II) (P = .046), an effect which was entirely attributable to noninvasive ventilation, and length of ICU stay decreased in survivors from 37 (21-71) to 25 (19-63) hours (P = .049). The amount of morphine (P = .001) and midazolam (P = .050) decreased, whereas the amount of propofol (P = .052) and fentanyl increased (P = .001). Total Therapeutic Intervention Scoring System-28 (TISS-28) per patient decreased from 137 (99-272) to 113 (87-256) points (P = .009). Intensive care unit mortality was 19% (baseline), 8% (implementation I), and 7% (implementation II) (P = .020). CONCLUSIONS: Changes in organizational and care processes were associated with an altered pattern of sedative and analgesic drug prescription, a decrease in length of (noninvasive) respiratory support and length of stay in survivors, and decreases in resource use as measured by TISS-28 and mortality.

Effects of prolonged endotoxemia on liver, skeletal muscle and kidney mitochondrial function.

INTRODUCTION: Sepsis may impair mitochondrial utilization of oxygen. Since hepatic dysfunction is a hallmark of sepsis, we hypothesized that the liver is more susceptible to mitochondrial dysfunction than the peripheral tissues, such as the skeletal muscle. We studied the effect of prolonged endotoxin infusion on liver, muscle and kidney mitochondrial respiration and on hepatosplanchnic oxygen transport and microcirculation in pigs. METHODS: 20 anesthetized pigs were randomized to receive endotoxin or saline infusion for 24 hours. Muscle, liver and kidney mitochondrial respiration was assessed. Cardiac output (thermodilution), carotid, superior mesenteric and kidney arterial, portal venous (ultrasound Doppler) and microcirculatory blood flow (laser Doppler) were measured, and systemic and regional oxygen transport and lactate exchange were calculated. RESULTS: Endotoxin infusion induced hyperdynamic shock and impaired the glutamate- and succinate-dependent mitochondrial respiratory control ratio (RCR) in the liver (glutamate: endotoxemia: median [range] 2.8 [2.3-3.8] vs. controls: 5.3 [3.8-7.0]; p<0.001; succinate: endotoxemia: 2.9 [1.9-4.3] vs. controls: 3.9 [2.6-6.3] p=0.003). While the ADP:O ratio was reduced with both substrates, maximal ATP production was impaired only in the succinate-dependent respiration. Hepatic oxygen consumption and extraction, and liver surface laser Doppler blood flow remained unchanged. Glutamate-dependent respiration in the muscle and kidney was unaffected. CONCLUSIONS: Endotoxemia reduces the efficiency of hepatic but neither skeletal muscle nor kidney mitochondrial respiration, independent of regional and microcirculatory blood flow changes.

Reproducibility of cerebral oxygenation measurement in neonates and infants in the clinical setting using the NIRO 300 oximeter.

OBJECTIVE: To study reproducibility of cerebral tissue oxygenation index (cTOI) values in neonates and infants in a clinical setting using the NIRO 300 oximeter (Hamamatsu Photonics, Hamamatsu City, Japan). DESIGN: Clinical, observational study. SETTING: University hospital, pediatric intensive care unit. PATIENTS: Twenty neonatal and pediatric intensive care patients (age 0-190 days; median 4.5 days). INTERVENTIONS: Reproducibility of cTOI was measured at the lateral forehead of the patients. MEASUREMENTS AND MAIN RESULTS: Sensor exchange experiments were performed by removing the sensor and reapplying another sensor (sensor 1 vs. sensor 2) at the same position. Simultaneous measurements, comparing cTOI values from the right and left forehead, were performed using both sensors. Corresponding sensor exchange experiments were performed within 10 mins. All tests were done under stable, steady-state cardiorespiratory conditions. Data were compared using Bland-Altman bias analysis and paired, two-sided Student's t-test (p < .05). Sensor exchange experiments and simultaneous left-to-right forehead measurements revealed only small mean differences (<5%) and no significant differences between corresponding values (p = .953/.164). However, Bland-Altman bias analysis revealed poor agreement with large 95% limits of agreement in particular for sensor exchange experiments (-17.8% to 17.6%) and less for simultaneous left and right measurements (-14.4% to 10.4%). CONCLUSIONS: The present study shows that cTOI measurements using the NIRO 300 oximeter at the lateral forehead of neonates and infants are not well reproducible under clinical conditions. This raises the question whether generally valid normal values can be defined with the used approach and makes it difficult to determine a normal range of cerebral oxygenation.

Near-infrared spectroscopic cerebral oxygenation reading in neonates and infants is associated with central venous oxygen saturation.

BACKGROUND: The aim of the study was to elucidate easily determinable laboratory and vital parameters in clinical practice to explain variability of near-infrared spectroscopic cerebral oxygenation readings in critically ill newborns and infants using the NIRO 300 spectrometer. METHODS: Near-infrared spectroscopy (NIRS) cerebral tissue oxygenation index (cTOI) was measured on the forehead of critically ill neonates and infants with existing arterial and/or central venous access. We recorded patient characteristics and simultaneously determined sedation state, hemodynamic, respiratory and laboratory data, such as arterial blood gas analysis, electrolytes, hemoglobin and arterial lactate concentration, blood glucose and central venous oxygen saturation. Data were compared using linear, multiple and forward stepwise regression analysis (P < 0.05). RESULTS: A total of 155 neonates and infants aged from 0 to 365 days (median 12 days) were studied. cerebral tissue oxygenation index (cTOI) values ranged from 32.1 to 91.0% (60.5 +/- 11.5%). Simple linear regression analysis revealed significant associations between cTOI and arterial oxygen saturation (r = 0.254, P = 0.001), transcutaneously measured arterial oxygen saturation (r = 0.320, P < or = 0.0001), central venous oxygen saturation (r = 0.489, P < 0.0001), arteriovenous oxygen extraction (r = 0.445, P < 0.0001) and presence of a cardiac shunt (r = 0.250, P = 0.024). Multiple regression analysis and forward stepwise regression revealed two independent, significant predictors for cTOI, namely SvO2 (P < 0.0001) and presence or absence of a cardiac shunt (P = 0.003). SvO2 alone explained 23.9% of the variability of cTOI. The addition of the variable 'cardiac shunt' improved the model to 33%. CONCLUSIONS: Based on our study results cerebral tissue oxygenation readings by the NIRO 300 near-infrared spectrometer is influenced by central venous oxygen saturation, which partially explains intersubject variability of NIRS cerebral oxygenation readings.

Tissue oxygenation monitoring during major pediatric surgery using transcutaneous liver near infrared spectroscopy.

BACKGROUND: The aim of the study was to compare liver tissue oxygenation determined by near infrared spectroscopy (NIRS) with central venous oxygen saturation (SvO(2)) and intestinal perfusion as measured by gastric intramucosal pH (pHi) in pediatric surgical patients. METHODS: Twenty children undergoing craniofacial surgery with expected major intraoperative blood loss were studied. NIRS tissue oxygenation index (TOI(Liver)) and pHi values were recorded. Arterial blood gas analysis and SvO(2) were assessed from periodically taken blood samples. Data are presented as ranges (median) and were compared using linear regression analysis. Sensitivity and specificity of the intra-individual changes in TOI(Liver) to predict falling SvO(2) or pHi values were calculated. RESULTS: Patients age ranged from 0.79 to 8.27 years (1.92 years). TOI(Liver) ranged from 41.5 to 77.4% (61.5%), gastric pHi from 7.13 to 7.60 (7.37) and SvO(2) from 51 to 86% (74%). Among patients only moderate correlation was found between TOI(Liver) and SvO(2) (r = 0.594, P < 0.0001) and gastric pH(i) (r = 0.502, P < 0.0001). Intra-individual measured TOI(Liver) values, however, demonstrated close correlation with SvO(2) values (r = 0.680 to 0.976) but a varying correlation with gastric pHi values (r = 0.055 to 0.972). Sensitivity/specificity of TOI(Liver) to predict decreasing SvO(2) or gastric pHi values were 76.4/73.4% and 67.4/62.7% respectively. CONCLUSIONS: TOI(Liver) provided a better trend monitor of central venous oxygen saturation than gastric intramucosal pH. Because of its limited sensitivity and specificity to indicate deterioration of SvO(2), liver tissue oxygenation measured by transcutaneous NIRS does not provide additional practical information for clinical management.

Blockade of NMDA receptor subtype NR2B prevents seizures but not apoptosis of dentate gyrus neurons in bacterial meningitis in infant rats.

BACKGROUND: Excitotoxic neuronal injury by action of the glutamate receptors of the N-methyl-d-aspartate (NMDA) subtype have been implicated in the pathogenesis of brain damage as a consequence of bacterial meningitis. The most potent and selective blocker of NMDA receptors containing the NR2B subunit is (R,S)-alpha-(4-hydroxyphenyl)-beta-methyl-4-(phenylmethyl)-1-piperid inepropanol (RO 25-6981). Here we evaluated the effect of RO 25-6981 on hippocampal neuronal apoptosis in an infant rat model of meningitis due to Streptococcus pneumoniae. Animals were randomized for treatment with RO 25-6981 at a dosage of either 0.375 mg (15 mg/kg; n = 28) or 3.75 mg (150 mg/kg; n = 15) every 3 h or an equal volume of sterile saline (250 microl; n = 40) starting at 12 h after infection. Eighteen hours after infection, animals were assessed clinically and seizures were observed for a period of 2 h. At 24 h after infection animals were sacrificed and brains were examined for apoptotic injury to the dentate granule cell layer of the hippocampus. RESULTS: Treatment with RO 25-6981 had no effect on clinical scores, but the incidence of seizures was reduced (P < 0.05 for all RO 25-6981 treated animals combined). The extent of apoptosis was not affected by low or high doses of RO 25-6981. Number of apoptotic cells (median [range]) was 12.76 [3.16-25.3] in animals treated with low dose RO 25-6981 (control animals 13.8 [2.60-31.8]; (P = NS) and 9.8 [1.7-27.3] (controls: 10.5 [2.4-21.75]) in animals treated with high dose RO 25-6981 (P = NS). CONCLUSIONS: Treatment with a highly selective blocker of NMDA receptors containing the NR2B subunit failed to protect hippocampal neurons from injury in this model of pneumococcal meningitis, while it had some beneficial effect on the incidence of seizures.