Measurement of cerebral blood volume using near-infrared spectroscopy and indocyanine green elimination.

Methods for measuring cerebral blood volume (CBV) have traditionally used radioisotopes. More recently, near-infrared spectroscopy (NIRS) has been used to measure CBV by using a technique involving O(2) desaturation of cerebral tissue, where the observed change in the concentration of oxygenated hemoglobin is a marker of the volume of blood contained within the brain. A new integration method employing NIRS is described by using indocyanine green (ICG) as the intravascular marker. After bolus injection, concentration-time integrals of cerebral tissue ICG concentration ([ICG](tissue)) measured by NIRS are compared with corresponding integrals of the cerebral blood ICG concentrations ([ICG](blood)) estimated by high-performance liquid chromatography of peripheral blood samples with allowance for cerebral-to-large-vessel hematocrit ratio. It is shown that CBV = integral [ICG]tissue/[ICG]blood. Measurements in 10 adult volunteers gave a mean value of 1.1 +/- 0.39 (SD) ml/100 g illuminated tissue. This result, although lower than previous NIRS estimations, is consistent with the long extracerebral path of light in the adult head. Scaling of results is required to take into account this component of the optical pathlength.

A comparison between the Fick method and indirect calorimetry for determining oxygen consumption in patients with fulminant hepatic failure.

OBJECTIVE: To compare the Fick method of determining oxygen consumption (VO2) with a gas exchange method in a group of patients in whom the cardiac output and mixed venous oxygen saturation values were consistently high. DESIGN: A prospective, observational study. SETTING: A ten-bed intensive therapy unit at a university teaching hospital. PATIENTS: Seventeen patients suffering from fulminant hepatic failure who required ventilatory support and invasive hemodynamic monitoring. All patients were sedated and paralyzed throughout the study period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: VO2 was determined simultaneously by indirect calorimetry and by the Fick method five or six times in each patient over a 5-hr period after resuscitation with fluids and, if clinically indicated, norepinephrine infusion. The agreement between the methods was poor (limits of agreement +19 to -101 mL/min/m2) and the Fick method consistently underestimated gas exchange measurements (mean bias 41 mL/min/m2). The bias varied widely, both between and within individual patients. The reproducibility of the Fick-derived VO2 was worse than the indirect calorimetry measurements, indicating that the dispersion of data attributable to measurement error was greater with the Fick method. CONCLUSIONS: Under clinical conditions, the agreement between Fick calculations and indirect calorimetry measurements of VO2 in hyperdynamic patients with fulminant hepatic failure was extremely poor. The reproducibility of Fick calculations was less than the reproducibility derived by gas exchange measurements because of the large measurement errors that may occur with the Fick method when the cardiac output is large and the arterial-venous oxygen content difference is small. Fick calculations systematically underestimate gas exchange measurements. The Fick method is inaccurate and unreliable when an estimation of VO2 is required in patients with this hemodynamic pattern.

Energy expenditure in acetaminophen-induced fulminant hepatic failure.

OBJECTIVE: To determine energy expenditure in critically ill patients suffering from acetaminophen-induced fulminant hepatic failure and compare it with values obtained in matched, healthy control subjects and in patients studied during the anhepatic period of elective liver transplantation. DESIGN: Prospective, controlled, observational study. SETTING: A ten-bed intensive therapy unit and a liver transplant unit at a University teaching hospital. PATIENTS AND SUBJECTS: Sixteen patients suffering from acetaminophen-induced fulminant hepatic failure who were sedated, paralyzed, and mechanically ventilated; 16 age-, gender-, and weight-matched, awake, healthy control subjects; and 16 patients with chronic liver disease, undergoing elective liver transplantation, who were studied during the anhepatic period of surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The mean energy expenditure was calculated in each case for a 30-min period, using indirect calorimetry. In the patients undergoing liver transplantation, measurements were performed after clamping the hepatic veins and recipient hepatectomy. Energy expenditure was markedly increased in the fulminant hepatic failure group (mean energy expenditure, 4.05 [SD 0.52] kJ x kg(-1) x hr(-1)), in comparison with healthy control subjects (mean, 3.44 [0.27] kJ x kg(-1) x hr(-1); mean difference, 18%; p < .001) and in comparison with patients during the anhepatic period of liver transplantation (mean, 3.15 [0.61] kJ x kg(-1) x hr(-1); mean difference, 29%; p < .001). These differences were even more pronounced when a correction factor for differences in core temperature was included in the calculation. Harris-Benedict predictions of energy expenditure were unreliable in the patients with acute liver failure. No correlations were found among energy expenditure and hemodynamic variables, the requirement for vasoconstrictors, or the presence of renal failure. CONCLUSIONS: Despite the loss of functioning liver cell mass, the metabolic rate is substantially increased in patients with acetaminophen-induced fulminant hepatic failure. This finding is consistent with the marked systemic inflammatory response, which accompanies acute hepatic failure. The Harris-Benedict equation is unreliable when an estimation of energy expenditure is required in patients with this condition.

The effect of N-acetylcysteine on oxygen transport and uptake in patients with fulminant hepatic failure.

We have investigated the effect of N-acetylcysteine on hemodynamic variables, oxygen delivery (DO2), oxygen consumption (VO2), and oxygen extraction in patients with fulminant hepatic failure using independent methods of determining DO2 and VO2, thereby eliminating the effect of mathematical coupling, which may have biased previous studies. In 11 patients with severe fulminant hepatic failure, we documented the hemodynamic effects of N-acetylcysteine during the first 5 hours of a standard infusion regime and simultaneously measured VO2 using a method based on respiratory gas analysis. We related physiological changes to plasma N-acetylcysteine concentrations, and compared this group with 7 patients who received placebo infusions. A variable hemodynamic response to N-acetylcysteine was observed that did not differ significantly in comparison with the placebo group, and did not correlate with plasma drug concentrations. The most significant relationship observed between DO2 and VO2 in any patient predicted a 13-mL x min(-1) x m(-2) increase in VO2 when DO2 increased by 100 mL x min(-1) x m(-2); in 8 patients, VO2 was independent of DO2 over the range observed. In the group that received N-acetylcysteine, a small (mean 6 [SD 6] mL x min(-1) x m[-2]) increase in VO2 occurred in comparison with baseline after 1 hour of infusion (P < .01), but changes were not significantly different from the placebo group and were not sustained. N-Acetylcysteine infusion did not increase oxygen extraction or result in an improvement in whole-blood lactate levels or base excess during the study period. We conclude that N-acetylcysteine infusion does not result in clinically relevant improvements in global VO2, or in clinical markers of tissue hypoxia in patients with severe fulminant hepatic failure.

Effect of graft reperfusion on haemodynamics and gas exchange during liver transplantation.

We have documented the changes in gas exchange, haemodynamic state and associated physiological variables which occurred after graft reperfusion in 20 patients undergoing uncomplicated orthotopic liver transplantation. Gas exchange was measured during constant ventilation using a metabolic monitor. After reperfusion, there were increases in VO2 (mean increase 57 (SD 25) ml min-1) (P < 0.001), VCO2 (mean increase 38 (17) ml min-1) (P < 0.001) and PaCO2 (mean increase 0.88 (0.56) kPa) (P < 0.001). These were associated with increases in cardiac output (1.2 (1.0) litre min-1 m-2) (P < 0.001) and mean pulmonary artery pressure (9 (6) mm Hg) (P < 0.001). There was a decrease in standard bicarbonate concentration (0.96 (1.6) mmol litre-1) (P < 0.02) and increase in hydrogen ion concentration (8.15 (5.9) mmol litre-1) (P < 0.001) consistent with the release of an acid load from the graft and previously ischaemic tissues. The increases in PaCO2 and hydrogen ion concentration were significantly larger in patients in whom venovenous bypass was used during the anhepatic period compared with the "piggyback" surgical technique. We found correlations between the changes in PaCO2 and VCO2 (r2 = 0.25, P < 0.02), cardiac output and VCO2 (r2 = 0.34, P < 0.01), and cardiac output and VO2 (r2 = 0.34, P < 0.01). We conclude that major alterations in gas exchange occur after reperfusion which result from alterations in metabolic rate and haemodynamic changes. These may be clinically relevant, particularly in patients at risk of cerebral oedema.

The Inter-Regional, Epidemiological Study of Childhood Cancer (IRESCC): case-control study in children with germ cell tumours.

In 1980-1983 members of IRESCC interviewed parents of 555 children with newly diagnosed cancer on topics of possible aetiological significance. Identical questions were asked of the parents of 1100 control children chosen from hospital admissions and general practitioner lists. Medical information was confirmed whenever possible by cross-checking with NHS records. Data for the 41 children with germ cell tumours and their 82 controls are reported here. The cases had more major congenital malformations than controls, including one neural tube defect. More case than control mothers and fathers reported occupational exposure to chemicals. Nine close relatives of cases had multiple primary tumours, which were often benign or of low-grade malignancy, compared with 1 hospital control and 3 general practitioner control relatives. Cases and controls differed with respect to birth weight and paternal age. No case-control differences were shown for: birth rank, maternal age, chronic illnesses and smoking, mothers' reproductive histories and oral contraceptive usage. In index pregnancies there were no case-control differences for maternal illness, infections, alcohol intake and X-ray and ultrasound exposure. There was no difference between cases and controls for the frequency of twinning the families.

The Inter-Regional Epidemiological Study of Childhood Cancer (IRESCO). Study design, control selection and data collection.

The Inter-Regional Epidemiological Study of Childhood Cancer (IRESCC) was established to investigate the role of possible aetiological factors in childhood cancer, with particular emphasis on environmental exposures to the foetus and family history of certain diseases including cancer. Incident cases occurring in three Health Service regions (the West Midlands, Yorkshire and North Western) were matched for age and sex with two sets of control children. A total of 555 cases and 1110 controls were entered into the study. The parents of each index child were interviewed with respect to events during the relevant pregnancy, occupation, smoking habits, and past medical history of themselves, the child's siblings and other relatives. Ninety-three per cent of case parents approached agreed to be interviewed, and approximately 90% of controls were ranked first or second on the control selection lists. After the interview information was verified by reference to antenatal and other medical records. Obstetric and general practitioner records were abstracted for approximately 90% of cases and controls. Information derived from the interview and that from medical records was coded separately. The data collected by each region have been pooled and case-control comparisons of potential aetiological factors will be carried out, using matched triplet analyses.

Inter-Regional Epidemiological Study of Childhood Cancer (IRESCC): childhood cancer and the consumption of debendox and related drugs in pregnancy.

Attention has recently focused on the possible teratogenic effects of the combination antiemetic doxylamine succinate, dicyclomine hydrochloride and pyridoxine hydrochloride (Debendox/Bendectin) prescribed to pregnant women. The Inter-Regional Epidemiological Study of Childhood Cancer (IRESCC), a case-control investigation has analysed data derived from interview reports and medical records of 555 mothers of children (under 15 years) with cancer and 1110 mothers of matched control children. Separate analyses of interview reports and medical records both suggested that antiemetic ingestion during the index pregnancy does not increase the risk of developing childhood malignant disease in the exposed foetus. No dose-response relationship was evident. The lack of any significant relative risks held good for diagnostic sub-groups and when the trimester of ingestion was considered. Our results suggest that antimetics of this type are unlikely to be transplacental carcinogens.

The inter-regional epidemiological study of childhood cancer (IRESCC): a case control study of aetiological factors in leukaemia and lymphoma.

The inter-regional epidemiological study of childhood cancer analysed data on 234 children diagnosed with leukaemia or lymphoma and 468 controls matched for age and sex. A wide range of potential risk factors was examined, including prenatal exposure to x rays, maternal drug ingestion and smoking, child's medical history, and parental medical conditions and occupation. Calculations were completed for leukaemia or lymphoma and diagnostic subgroups, as defined by laboratory confirmed cell type. In utero exposure to narcotic analgesics was weakly associated with leukaemia or lymphoma but no other antenatal factors gave significant risks. New associations were identified for skin diseases in both parents and congenital abnormalities in the mothers of children with leukaemia. For past medical conditions in the child, viral disease occurring under 6 months of age increased the risk for acute lymphoblastic leukaemia. Fewer children in the leukaemia or lymphoma group had been immunised compared with the control groups. Case children diagnosed over the age of 9 years were more likely than controls to have had four or more previous episodes of illness. Overall, these results indicate that prenatal factors may be less important than postnatal or genetic influences in the development of leukaemia or lymphoma in children.

Ultrasound examinations in pregnancy and childhood cancer.

Analysis of information obtained in an inter-regional epidemiological study by interviewing the parents of 555 children with malignancy diagnosed between 1980 to 1983 and the parents of 1110 control children did not reveal any significant association between exposure to ultrasound examination in pregnancy and risk of childhood cancer.