Resistance of the new-born to injury.
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Biomedical subjects
Publications and source records attributed to R A Little.
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1. The changes in blood haemoglobin concentration, great vessel haematocrit value, red cell volume, plasma volume and total blood volume have been studied in rabbits from birth to 4 months of life.2. The plasma volumes were measured with [(131)I]human serum albumin and/or rabbit serum [(14)C]albumin. Red cell volumes were measured with [(51)Cr]-rabbit red blood cells. Blood volumes were also calculated from carbon clearance curves.3. The haemoglobin concentration and the great vessel haematocrit value fell during the first 11 days of life. The great vessel haematocrit value was then not significantly different from the value at 4 months; whereas the haemoglobin concentration fell further until 22 days, when it started to rise towards the concentration at 4 months.4. The true plasma volume could not be accurately measured during the first 48 hr of life by the injection of labelled albumin since it rapidly equilibrated with an extravascular albumin space. As the ratio of the whole body haematocrit to the great vessel haematocrit (F(cells)) did not appear to change with age the plasma volume at this time was best obtained by calculation from the red volume and corrected great vessel haematocrit.5. The blood volume fell significantly during the first 4 months of life due to significant falls in the red cell and plasma volumes.
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STUDY OBJECTIVE: To evaluate the relationship between the shock index SI (ratio of heart rate to systolic arterial pressure) and cardiac function and oxygen transport in an experimental model of hemorrhage and clinical septic shock. METHODS AND RESULTS: This study was conducted in a hypovolemic circulatory failure model; 40% hemorrhage in the anesthetized pig and normovolemic hyperdynamic septic patients in the intensive care unit (ICU). Hemodynamic and oxygen transport variables were measured and their relationships to SI was examined. SI was inversely related to blood loss, cardiac index (CI), stroke volume (SV), mean arterial pressure (MAP) and left ventricular stroke work (LVSW) (r = -0.73, -0.75, -0.89 and -0.75, respectively P less than 0.01) following hemorrhage in the anesthetized pig. Oxygen transport variables, i.e. oxygen delivery (DO2) and mixed venous oxygen saturation (SvO2P) (r = -0.68 and -0.74, respectively, P less than 0.01) were also inversely related to the SI. Oxygen consumption (VO2) increased initially with increasing SI and fell when SI was greater than 3.0. In clinical septic shock and following blood volume expansion, the SI was not correlated to CI, SVI, MAP or systemic vascular resistance (SVR) (r = -0.01, -0.47, -0.34 and -0.14, respectively, P-value NS) but was inversely related to LVSWI (r = -0.68, P less than 0.01). There were no relationships between the SI and oxygen transport variables (DO2, SvO2) (r = -0.02 and -0.17, P-value NS) in septic shock. CONCLUSION: SI provides a non-invasive means to monitor deterioration or recovery of LVSW during acute hypovolemic and normovolemic circulatory failure and its therapy. SI may be of limited value in the assessment of systemic oxygen transport and response to therapy in clinical shock.
Although nutritional support is vital to treatment of severe sepsis, the septic patient does not respond normally to glucose infusion. We have used the hyperglycemic glucose clamp technique to investigate the initial hormonal and metabolic responses of the septic patient to glucose under controlled conditions. The plasma glucose concentration was raised to and maintained at 12 mmol/liter for 2 hr in 12 septic patients and 11 normal controls. Glucose utilization, assessed from the amount infused, was significantly depressed in the patients, despite similar plasma insulin concentrations in the two groups. Forearm glucose uptake was similarly impaired. Despite very similar plasma free fatty acid concentrations in the two groups, which were suppressed equally by the glucose infusion, whole-body fat oxidation was elevated in the patients compared with the controls, and suppressed to a lesser extent in response to glucose. Glycerol and ketone body concentrations were elevated in the patients in keeping with a picture of accelerated release, clearance, and oxidation of fatty acids. Plasma cortisol, epinephrine, and norepinephrine concentrations were elevated in the septic patients in a severity-related manner, but not to high levels compared with experimental work. Norepinephrine showed no response to the glucose infusion in either group. Plasma glucagon concentrations were not significantly elevated in the septic patients. We conclude that the hyperglycemic glucose clamp provides a useful model for studying glucose intolerance in sepsis. Impaired glucose utilization in septic patients is associated with increased fat oxidation, although the hormonal basis for these changes is still unclear.
Metabolic complications of total parenteral nutrition can occur in several ways. Some of them, such as vitamin deficiencies, are easily foreseen and so avoided. Others can arise from the administration of excess calories, particularly in the form of glucose. Normally excess glucose inhibits fat oxidation and promotes lipid synthesis, so that the respiratory quotient rises about 1.0. In seriously ill, septic patients the main fuel is fat and its oxidation is not inhibited by excess glucose. Large amounts of O2 are required and large amounts of CO2 produced. By measuring the patient's resting energy expenditure, respiratory quotient and ventilatory equivalents one can assess his caloric requirements and whether or not he will have difficulty excreting the CO2 produced. If the stress on the pulmonary system appears too great CO2 production can be decreased by increasing the proportion of calories given as fat.