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Biomedical subjects

P Nightingale

Publications and source records attributed to P Nightingale.

At least 19 recordsLinked to original sources

Sex mismatch as a risk factor for chronic rejection of liver allografts.

Chronic irreversible rejection is a major cause of graft loss and retransplantation after orthotopic liver allotransplantation. To identify risk factors we retrospectively analysed 423 adult consecutive primary liver allograft recipients. The endpoint of the study was graft failure due to chronic rejection leading either to retransplantation or death. Chronic rejection developed in 22 (5.2%) patients. Pretransplant diagnosis of primary biliary cirrhosis or autoimmune hepatitis, recipient age less than 30 years, 1 or more episodes of acute cellular rejection, and transplantation of an organ from cytomegalovirus (CMV). IgG positive donor to an IgG negative recipient were identified as risk factors for chronic rejection. Transplantation of a liver from a male donor into a female recipient was also associated with an increased probability of chronic rejection. By logistic regression analysis, the probability of chronic rejection was predicted by: sex and cytomegalovirus match of donor and recipient, the presence of acute rejection, recipient age, transplantation for autoimmune hepatitis or primary biliary cirrhosis, and recipients receiving no azathioprine during the third month after transplantation. Sensitisation to antigens expressed by bile-duct epithelium as in primary biliary cirrhosis or exposure to donor bile-duct minor histocompatibility antigens, such as the male sex related H-Y antigen, may provide an explanation. More selective allocation of donor organs may allow a reduction in the incidence of ductopaenic rejection and graft loss.

ABO Blood-Group System

Comparison of the hemodynamic and oxygen transport responses to modified fluid gelatin and hetastarch in critically ill patients: a prospective, randomized trial.

OBJECTIVE: To compare the hemodynamic and oxygen transport responses to a rapid (< 10-min) infusion of 500 mL of modified fluid gelatin (group A) or hydroxyethyl starch (group B) in patients suffering from acute hypovolemia. DESIGN: Prospective, randomized, noncrossover study. SETTING: University hospital, general intensive care unit. PATIENTS: Twenty-eight patients with hypovolemia mechanically ventilated for concurrent acute respiratory failure. INTERVENTIONS: Patients were mechanically ventilated. Pulmonary and femoral artery catheters were used for hemodynamic monitoring. MEASUREMENTS AND MAIN RESULTS: Hemodynamic and oxygen transport variables were determined at baseline, 15 mins, and 30 mins after the infusion of each fluid. In both groups pulmonary artery occlusion pressure, stroke volume, and cardiac index significantly increased. In neither group did heart rate decrease. Oxygen delivery increased significantly in group A patients but not in group B patients. This result was due to greater hemodilution in group B patients. CONCLUSIONS: There are no significant differences in the hemodynamic responses to hydroxyethyl starch or modified fluid gelatin. The hemodynamic and oxygen transport effects of artificial colloid solutions may not be entirely predictable and should be monitored in critically ill patients.

Adult

The need for quality control in measurement of mixed venous oxygen saturation.

We investigated the variability of arterial, mixed venous and peripheral venous oxygen saturation readings in three co-oximeters in regular use on two Intensive Care Units. Over a 2-week period, 96 readings were obtained from each of the following machines; two AVL 912 co-oxylite co-oximeters (Machines A and B, Biomedical Instruments, Graz, Austria) and one IL-282 (Machine C, Instrumentation Laboratories, Lexington, MA, USA). The coefficient of variation in the arterial oxygen saturations was extremely small on all three machines (< 0.43%). The coefficient of variation in the mixed venous samples, however, ranged from 1.96 to 4.61% on machine A, and from 2.73 to 4.71% on machine B, but only from 0.17 to 1.47% on machine C. The variation in mixed venous saturations obtained from a single blood sample repeatedly analysed on machines A and B was large enough to influence clinical management.

Humans

Influence of an anti-tumor necrosis factor monoclonal antibody on cytokine levels in patients with sepsis. The CB0006 Sepsis Syndrome Study Group.

OBJECTIVES: To determine the safety, pharmacokinetics, and activity of an anti-tumor necrosis factor (TNF)-alpha monoclonal antibody in severe sepsis. DESIGN: Open-label, prospective, phase II multicenter trial with escalating doses of a murine monoclonal antibody (CB0006). SETTING: Twelve academic medical center intensive care units in the United States and Europe. PATIENTS: Eighty patients with severe sepsis or septic shock who received standard supportive care and antimicrobial therapy in addition to the anti-TNF antibody. INTERVENTIONS: Patients were treated intravenously with one of four dosing regimens with CB0006: 0.1 mg/kg, 1.0 mg/kg, 10 mg/kg or two doses of 1 mg/kg 24 hrs apart. MEASUREMENTS AND MAIN RESULTS: The murine monoclonal anti-TNF antibody was well tolerated despite the development of anti-murine antibodies in 98% of patients. No survival benefit was found for the total study population, but patients with increased circulating TNF concentrations at study entry appeared to benefit by the high dose anti-TNF antibody treatment. Increased interleukin (IL)-6 levels predicted a fatal outcome (p = .003), but TNF levels were not found to be a prognostic indicator. TNF levels were higher (206.7 +/- 60.7 vs. 85.9 +/- 26.1 pg/mL; p < .001) and outcome was poor (41% vs. 71% survival; p = .007) in patients who were in shock at study entry when compared with septic patients not in shock. CONCLUSIONS: The murine anti-TNF-alpha monoclonal antibody CB0006 has proven to be safe in this clinical trial and may prove to be useful in septic patients with increased circulating TNF concentrations. Further studies are needed to determine efficacy and the ultimate clinical utility of this immunotherapeutic agent in sepsis.

Antibodies, Monoclonal

Early cardiorespiratory findings after severe blunt thoracic trauma and their relation to outcome.

This study examined the initial haemodynamic and oxygen transport patterns in 24 patients with severe blunt thoracic trauma in whom immediate monitoring with femoral and pulmonary artery catheters was required after admission to the intensive care unit. All patients required mechanical ventilation and were studied before receiving inhalational anaesthesia and within 12 h of injury. Two groups of patients were identified; nine patients (group 1) had an impaired left ventricular stroke work index (LVSWI) and 15 patients had a normal LVSWI (group 2). There were no significant differences in the abbreviated injury scale score for the chest, the total injury severity score, or the mean ages of the two groups. There were significant differences in stroke volume index, 32 versus 56 ml m-2 (P less than 0.001), and cardiac index, 3.2 versus 5.3 l min-1 m-2 (P less than 0.001), and therefore in oxygen delivery, 469 versus 852 ml min-1 m-2 (P less than 0.001), despite apparently adequate volume expansion using the same protocol and clinical criteria in both groups. Oxygen consumption was not significantly different in the two groups, 135 versus 157 ml min-1 m-2, because of a higher oxygen extraction ratio in group 1, 29 versus 19 per cent (P less than 0.001), and hence lower mixed venous oxygen saturation, 73 versus 82 per cent (P less than 0.02). Seven patients in group 1 died (78 per cent) compared with two in group 2 (13 per cent). Early depression of cardiac function is associated with poor outcome in patients with thoracic trauma, and measurements of oxygen transport variables may influence resuscitation and the timing of surgical procedures.

Cardiac Output

Computerised protocols for laboratory investigation and their effect on use of medical time and resources.

AIMS: To devise a computerised management system protocol which not only proposes the laboratory investigations to be performed on each patient but also performs related clinical functions. METHODS: The system was designed by senior members of staff. The protocols defined all laboratory investigations including haematology, biochemistry, immunology and cross-matching, and included static and dynamic rules. Patients can be changed to different or additional protocols, as required; likewise proposed tests can be deleted or added. The software is written in MUMPS and runs on a 386 PC running MSM MUMPS under MSDOS. RESULTS: The number of clinical chemistry tests requested per patient per day fell by 9.5% (p less than 0.01) for transplant recipients and by 28.8% (p less than 0.01) for non-transplant recipients. The average time spent by junior medical staff requesting laboratory investigations and enquiring about results fell from 10 minutes per patient per day to 4.1 minutes (p less than 0.001). CONCLUSIONS: The introduction of this system in no way abrogates clinicians' responsibility for the management of patients, because all proposed investigations must be confirmed or modified by the authorising doctor. The system allows for the audit of requesting patterns and subsequent improvement in protocols by recording any alterations made to the proposed investigations. Significant benefits in terms of better use of house officer time and medical resources were also achieved.

Clinical Laboratory Information Systems

Persistence of supply dependency of oxygen uptake at high levels of delivery in adult respiratory distress syndrome.

OBJECTIVE: To identify any plateau in oxygen consumption (VO2) when oxygen delivery (DO2) is increased in patients with the adult respiratory distress syndrome (ARDS). DESIGN: Clinical prospective study; multiple regression analysis was done to assess the relationship between VO2 and DO2 for pooled data and for each individual patient. SETTING: University hospital ICU. PATIENTS: Twenty consecutive patients aged 18 to 78 yrs (mean 43.5) in whom ARDS was present during their ICU stay. INTERVENTIONS: Multiple measurements were obtained in individual patients (mean number of measurements 40, range 20 to 83) and mathematical models were fitted to both pooled and individual patient data. DO2 ranged from 212 to 1550 mL/min.m2 with a maximum of 758 to 1550 mL/min.m2 (mean 1136). Because of the large variations between patients, it was not justifiable to describe a relationship for the pooled data and each case was analyzed individually. MEASUREMENTS AND MAIN RESULTS: We found the optimal regression model to be linear in 13 patients, cubic in four, and either cubic or linear in one. Two patients demonstrated no significant relationship. The relationship for the group was determined from each patient's data and was best described by linear regression. CONCLUSIONS: In no patient was there evidence of a plateau, despite high levels of DO2 being achieved in all patients.

Adolescent

Mechanism of shock associated with right ventricular infarction.

Various mechanisms have been proposed to explain the shock sometimes associated with right ventricular infarction, but only small numbers of patients with clinical shock have been studied. The haemodynamic profiles of seven patients with clinical cardiogenic shock after right ventricular myocardial infarction were studied prospectively. They were selected because all had a stable cardiac rhythm and none had absolute hypovolaemia during the study period. In all of them the mean right atrial pressure exceeded the pulmonary artery occlusion pressure. After treatment with varying combinations of dopamine, dobutamine, and glyceryl trinitrate (titrated to achieve the optimum haemodynamic response) the mean systemic arterial pressure increased, as did the cardiac index. There was an associated increase in the left ventricular stroke work index but the right ventricular stroke work index was unchanged. There was no significant change in heart rate, mean right atrial pressure, or pulmonary artery occlusion pressure. This suggests that the probable mechanism of the shock associated with right ventricular infarction is concomitant severe left ventricular dysfunction.

Aged

Hemodynamic and oxygen transport variables in cardiogenic shock secondary to acute myocardial infarction, and response to treatment.

There are few data on oxygen transport in cardiogenic shock after acute myocardial infarction. This prospective study examined oxygen transport variables in 19 such patients and assessed their responses to treatment. Femoral and pulmonary arterial catheters were inserted before any therapy except correction of hypoxemia by mechanical ventilation in 8 patients, defibrillation (3 patients) or pacing (5 patients). In 3 patients mean arterial pressure was greater than 80 mm Hg and cardiac index greater than 2.1 liters/min/m2 with normal mixed venous oxygen saturation despite simultaneous clinical shock. They recovered with no further treatment. Sixteen patients were treated with varying combinations of intravenous fluids and dobutamine (37 +/- 25 mu/kg/min) and 14 survived long enough for a second set of measurements to be completed. Mean heart rate increased from 83 +/- 22 to 101 +/- 20 beats/min and mean cardiac index from 1.4 +/- 0.5 to 2.5 +/- 0.4 liters/min/m2 (p less than 0.001). Oxygen consumption (VO2) was maintained even when oxygen delivery (DO2) was less than 330 ml/min/m2. After treatment DO2 increased from 230 +/- 69 to 397 +/- 60 ml/min/m2 (p less than 0.001) and VO2 from 103 +/- 31 to 124 +/- 27 ml/min/m2 (p less than 0.05). Mean mixed venous oxygen saturation increased from 54 +/- 16 to 69 +/- 8% (p less than 0.001) and mean oxygen extraction ratio decreased from 48 +/- 16 to 31 +/- 6% (p less than 0.001). There was no correlation between cuff systolic blood pressure and mean arterial pressure before or after resuscitation. Thirteen patients survived to hospital discharge. When cardiogenic shock responds to treatment, large increases in DO2 lead to small increases in VO2 but large increases in mixed venous oxygen saturation, reflecting improved tissue oxygen availability.

Aged

Practical points in the application of oxygen transport principles.

Application of the principles of oxygen transport in the management of critically ill patients can influence the frequency of organ failure and outcome. Adequate tissue oxygen consumption in these patients may depend on a supranormal level of oxygen delivery. The equations used for calculating oxygen delivery and consumption are provided, and it is noted that clinicians should have a clear understanding of the limitations of each of the measurements included in the equations. The methods used to perform the measurements are reviewed. Widespread acceptance and use of oxygen transport protocols in treatment is only possible if the measurements on which they are based are accurate and properly interpreted.

Critical Care

A critical study of the APACHE II scoring system using earlier data collection.

The APACHE II severity of illness scoring system was prospectively studied on 756 patients admitted to a general intensive care unit (ICU) from January 1986 to June 1988. Admission data were used. Individual and group risk of death were calculated for 3 diagnostic categories commonly seen in the A&E department and requiring admission to an ICU. The APACHE II score on admission tended to underestimate the risk of death following operative and non-operative trauma, and self-poisoning. This may have been related to the use of an analysis not yet validated against values obtained on admission to ICU. Such validation is urgently needed on a UK population if APACHE II scoring is to be of value in the A&E department.

Adolescent