The effects of high dose methylprednisolone or fluid volume expansion on cerebral haemodynamics and oxygen uptake in endotoxic shock. An experimental study in dogs.

E coli endotoxin has been shown to decrease cerebral blood flow (CBF) and increase cerebral metabolic rate of oxygen (CMRO2) in normocapnic dogs. The aim of this study was to investigate the effects of different clinical treatments on the cerebral and central circulation already under the influence of endotoxin. Thus the animals were treated with either methylprednisolone or a lactated Ringer's solution. CBF, CMRO2 and intracranial pressure were followed. Central haemodynamic parameters, i.e. cardiac output, aortic pressure and pulmonary artery pressure, were also measured. Five dogs were given methylprednisolone (Solu-Medrol) 30 mg/kg 90 min after the endotoxin injection. Following this drug there were no significant changes in CBF when compared to controls. The primarily increased CMRO2 did, however, show a transient decrease. Five animals were treated with a lactated Ringer's solution. (Ringerdex), 30 mg/kg, given intravenously over 20 min starting 90 min after the endotoxin injection. In these animals, the cardiac output as well as CMRO2 returned to the values before endotoxin. CBF did not increase significantly.

Effects of dopamine of cerebral circulation and oxygen metabolism in endotoxic shock: an experimental study in dogs.

Experimental endotoxic shock in normocapnic dogs decreases cerebral blood flow (CBF) and increases cerebral metabolic rate of oxygen (CMRO2). In 6 animals, an iv injection of 1.0-1.5 mg/kg of Escherichia coli endotoxin was followed by iv infusion of dopamine HCI at a rate of 3-24 Micrograms/kg . min. Doses of only 5 micrograms/kg . min maximally increased both CBF and CMRO2. There were no significant changes in cardiac output and whole body oxygen consumption. Mean aortic pressure and mean pulmonary artery pressure increased slightly after doses of 20 micrograms/kg . min. Results indicate that damage to the blood-brain barrier (BBB) after endotoxin administration allowed circulating monoamines to directly influence cerebral metabolisms.

Circulatory effects of carbon dioxide in experimental endotoxic shock.

In seven anaesthetized dogs the central circulatory effects of changes in Paco2 were studied before and after an intravenous injection of E. coli endotoxin 1.0 mg kg-1. The animals were on controlled ventilation with constant minute volumes, and Paco2 was changed by variations in the inspired gas mixture. Before endotoxin was given, cardiac output, mean aortic pressure, mean pulmonary artery pressure, total peripheral resistance and stroke volume were little affected by the changes in Paco2 from 3.9 +/- 0.4 to 7.2 +/- 0.4 kPa (mean +/- s.e.mean). Only heart rate decreased significantly (P less than 0.05). The intravenous endotoxin injection resulted in a decreased cardiac output (P less than 0.01), a decreased mean aortic pressure (P less than 0.01) and a decreased stroke volume (P less than 0.05). Mean pulmonary artery pressure, total peripheral resistance and heart rate showed only minor changes. In endotoxic shock an increase in Paco2 from 4.4 +/- 0.4 to 7.8 +/- 0.3 kPa (mean +/- s.e.mean) resulted in a significant increase in cardiac output (P less than 0.05), stroke volume (P less than 0.05) and mean pulmonary artery pressure (P less than 0.05), while the other parameters remained unchanged. It can be concluded that the carbon dioxide tension is of importance for the cardiac performance in experimental endotoxic stock in a manner not seen in control animals. The mechanisms behind these findings need further investigation.

Cerebral effects of HDC.

HDC is commonly used in conditions with a raised intracranial pressure. An effect on cerebral edema was first described in patients with brain tumors, where the intracranial pressure can be lowered following administration of HDC. However, the use of HDC in cerebral edema of other origin is not equally well supported. Apart from effects on brain circulation secondary to the effects of HDC on brain edema, direct effects of HDC on cerebral blood flow and oxygen uptake have been studied mainly in experimental endotoxic shock. Endotoxin given intravenously leads to reduction in the cerebral blood flow and increase in the oxygen uptake. The increased oxygen uptake could be due to circulating catecholamines or other substances affecting the cerebral metabolism following their passage of a damaged blood-brain barrier. Pretreatment with HDC prevents the effects of endotoxin on cerebral blood flow and oxygen uptake. When HDC was given after an intravenous endotoxin injection blood flow was unaffected but the increased cerebral oxygen uptake was reduced transiently. This might hypothetically be explained by either a direct effect on the permeability of the blood-brain barrier or indirectly via a decrease of metabolically active circulatory substances.

Cerebral function monitoring: a method of predicting outcome in term neonates after severe perinatal asphyxia.

The cerebral function monitor (CFM), a simplified one-channel EEG monitor, was evaluated in predicting outcome after severe perinatal asphyxia in 38 term infants. Survivors were followed until 1.5-2.5 years of age. All those 17 infants who survived without major neurological handicap showed continuous activity on the CFM trace during the first and/or second day of life. Twenty of the 21 infants who either died or developed severe neurological damage had burst suppression or paroxysmal activity on the first or second day of life. Thus cerebral function monitoring can be a valuable tool in predicting prognosis for infants with severe perinatal asphyxia.

Aminophylline reversal of diazepam sedation.

A double-blind randomised study was performed to investigate whether aminophylline reversed the sedative effect of diazepam. Thirty-two patients undergoing genito-urinary surgery with spinal or topical anaesthesia were given diazepam to maintain a state of deep sedation. Postoperatively patients received either aminophylline (60-120 mg) or physiological saline intravenously. The aminophylline group showed a rapid reversal of sedation, which persisted throughout the observation period of 2 hours. No such effect was seen in the patients who received saline and the difference was still obvious after 2 hours. It is concluded that aminophylline is a potent antagonist to the sedative effect of diazepam.

Effects of nitrous oxide/oxygen inhalation on the maternal circulation during vaginal delivery.

The hemodynamic changes occurring during the first stage of labor were studied in 24 healthy pregnant women during inhalation of different nitrous oxide/oxygen (N2O/O2) gas mixtures (intermittent 70/30, 40/60, 0/100 and continuous 40/60). Cardiac output increased (P less than 0.01) from 6.6 +/- 0.2 l/min between uterine contractions to 8.5 +/- 0.3 l/min during contractions. Heart rate, stroke volume, systolic, diastolic and mean arterial pressures were increased (P less than 0.01) and total peripheral vascular resistance was reduced (P less than 0.01) during contractions compared to measurements performed between contractions. The maternal circulation was influenced by the use of N2O/O2. During intermittent inhalation, higher concentrations of N2O were associated with a decrease (P less than 0.01) in heart rate, cardiac output and arterial pressure as well as an increase (P less than 0.01) in stroke volume. The degree of pain relief also increased (P less than 0.01) with increasing concentrations of inhaled nitrous oxide. The circulatory influence of intermittent inhalation given during uterine contractions was also apparent during the interval between contractions when N2O/O2 was not administered. The most obvious effects on both circulation and pain were demonstrated during continuous inhalation of N2O/O2. There was a close association between analgetic and cardiovascular effects indicating that the latter, at least partly, were due to pain relief. However, it was not possible to exclude or confirm possible direct pharmacological effects of N2O/O2 on maternal circulation.

Cerebral blood flow, cerebrovascular resistance and cerebral metabolic rate of oxygen in severe arterial hypoxia in dogs.

Cerebral blood flow and cerebral oxygen uptake were studied during severe arterial hypoxia in anesthetized dogs. It was shown that the hypoxic vasodilatation in the brain reaches a limit at an arterial oxygen saturation at about 25% and that this vasodilatation is less than that which may be induced by hypercapnia. A further deepening of the arterial hypoxia at a maintained cerebral perfusion pressure is combined with a continuous decrease in cerebral venous oxygen tension and a reduced oxygen uptake.

Cerebral blood flow, cerebrovascular resistance, cerebral metabolic rate of oxygen and intracranial pressure during and after severe prolonged arterial hypoxia in dogs. The role of dopamine in the deep hypoxic state.

The effect of extreme, prolonged arterial hypoxia on cerebral blood flow, oxygen uptake and intracranial pressure was studied in anesthetized dogs. The experiments were performed along two lines. Both started with a period of hypoxia of about 40 minutes to 2 hours. Thereafter normoxia was restituted in one group and the animals were studied for another 1-2 hours. In the other group with continued hypoxia dopamine was administered. During the hypoxic period the cerebral blood flow decreased mainly as a result of vasoconstriction after an initial marked flow increase. Cerebral oxygen uptake was reduced. Intracranial pressure increased, largely in proportion to blood flow changes, and no indication of important brain edema appeared. In the "recovery" period at normoxia the cerebral oxygen uptake showed an increase during the observation time. The blood flow, initially high, returned to the control level within the observation period. Dopamine infusion during continued hypoxia induced a vasodilatation, with reduction of vascular resistance to the values found at the induction of hypoxia, and with an increase of the cerebral oxygen uptake. An important role of endogenous dopamine in the hypoxic vasodilatation is suggested.

Studies on the influence of monoamines on the cerebrovascular response to arterial hypoxia.

The cerebrovascular response to arterial hypoxia was studied during blockade of the vascular dopamine receptors and during alpha-adrenergic receptor stimulation and blockade in anaesthetized dogs. Dopamine receptor blockade with pimozide or haloperidol invariably decreased the degree of hypoxic vasodilatation in the brain pointing to a functional role of dopamine in this situation. Alpha-receptor blockade did not change the response, while stimulation of these receptors decreased the dilatory response even in deep arterial hypoxia.

The effect of chlorpromazine in severe hypoxia in newborn infants.

Eighteen newborn infants with severe hypoxia during the course of idiopathic respiratory distress syndrome, pneumonia, persistent fetal circulation or right diaphragmatic hernia were treated with chlorpromazine with the aim of improving arterial oxygenation by a postulated vasodilatory action on the pulmonary circulation. Fourteen of the infants improved their PaO2 during the treatment. Nine infants died. The systemic arterial blood-pressure and the urinary output were reduced and some infants were somnolent during the initial period of treatment. No other side effects were noted. Further studies of chlorpromazine as a possible pulmonary vasodilator in newborn infants are justified.