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Biomedical subjects

M M Todd

Publications and source records attributed to M M Todd.

At least 127 records · Page 7Linked to original sources

A comparison of the direct cerebral vasodilating potencies of halothane and isoflurane in the New Zealand white rabbit.

Halothane is commonly viewed as a more potent cerebral vasodilator than isoflurane. It was speculated that the lesser vasodilation caused by isoflurane might be the result of the greater reduction in cerebral metabolic rate (CMR) that it causes, and that the relative vasodilating potencies of halothane and isoflurane would be similar if the two agents were administered in a situation that precluded volatile-agent-induced depression of CMR. To test this hypothesis, cerebral blood flow (CBF) and the cerebral metabolic rate for oxygen (CMRO2) were measured in two groups of rabbits before and after the administration of 0.75 MAC halothane or isoflurane. One group received a background anesthetic of morphine and N2O, which resulted in an initial CMRO2 of 3.21 +/- 0.17 (SEM) ml X 100 g-1 X min-1; second group received a background anesthetic of high-dose pentobarbital, which resulted in an initial CMRO2 of 1.76 +/- 0.16 ml X 100 g-1 X min-1. In rabbits receiving a background of morphine sulfate/N2O, halothane resulted in a significantly greater CBF (65 +/- 10 ml X 100 g-1 X min-1) than did isoflurane (40 +/- 5 ml X 100 g-1 X min-1). Both agents caused a reduction in CMRO2, but CMRO2 was significantly less during isoflurane administration. By contrast, with a background of pentobarbital anesthesia, CBF increased by significant and similar amounts with both halothane and isoflurane.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗

The response of the feline cerebral circulation to PaCO2 during anesthesia with isoflurane and halothane and during sedation with nitrous oxide.

The reduction in cerebral blood flow (CBF) caused by hypocapnia is an important element of neuroanesthetic techniques. While it has been demonstrated previously that the CO2 response of the cerebral circulation (CO2 X R) is enhanced (i.e., greater delta CBF/delta PaCO2) during halothane administration, the effect of isoflurane on CO2 X R has not been evaluated completely. Accordingly, the authors examined CO2 X R in cats during anesthesia with 1.0 MAC isoflurane (with 75% N2O) and compared it with CO2 X R during anesthesia with 1.0 MAC halothane (with 75% N2O) and with CO2 X R during the administration of 75% N2O alone. CO2 X R during anesthesia with isoflurane-N2O was enhanced relative to that observed during administration of both halothane-N2O (P less than 0.025) and N2O alone (P less than .001). CO2 X R during anesthesia with halothane-N2O was, in turn, greater than that observed during the administration of N2O alone (P less than 0.025). Furthermore, at similar levels of hypocapnia (PaCO2 18-20 mmHg), CBF was significantly lower (P less than 0.01) during administration of isoflurane-N2O (29.0 +/- 4.5 ml X 100 g-1 X min-1) than during administration of either N2O (40.6 +/- 5.5 ml X 100 g-1 X min-1) or halothane-N2O (39.6 +/- 7.8 ml X 100 g-1 X min-1). CBF values during administration of the N2O alone and halothane-N2O were not different during hypocapnia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The effect of high dose sodium thiopental on brain stem auditory and median nerve somatosensory evoked responses in humans.

Median nerve somatosensory evoked potentials (MnSSEPs), brain stem auditory evoked responses (BAERs), and the cortical electro-encephalogram (EEG) were recorded in six patients during a 62-min infusion of sodium thiopental (STP) at a rate of 1.25 mg X kg-1 X min-1 (total dose, 77.5 mg/kg). The EEG became isoelectric after 22 +/- 8 (SD) min of STP infusion. Dose-related changes in the latencies and amplitudes of various evoked response wave forms were observed. However, in no instance was any component of either the MnSSEP or the BAER rendered unobtainable by STP administration. For the MnSSEP, progressive increases in the central conduction time (5.33 +/- 0.41 ms preinduction vs. 7.46 +/- 1.2 ms at t = 60 min) and in the latency of the cortical primary specific complex were observed simultaneously with significant reductions in the amplitude of the latter (2.10 +/- 0.85 muV preinduction vs. 0.85 +/- 0.55 muV at t = 60 min). Changes in the latency and amplitude of the response recorded over the upper cervical spine (C2) were not statistically significant in this small population. For the BAER, progressive and significant increases in the latencies of Waves I, III, V (e.g., Wave V latency: 6.16 +/- 0.24 vs. 6.87 +/- 0.31 ms) and in the I-III, III-V, and the I-V interwave latencies were observed. The amplitudes of the BAER components were not significantly altered. The authors conclude that the administration of a dose of STP in excess of twice that required to produce EEG isoelectricity can be compatible with effective monitoring of MnSSEPs and BAERs. However, STP produces dose-related changes in both evoked response wave forms, which must be considered in the interpretation of responses elicited during STP anesthesia.

Adult↗

Cerebrovascular effects of prolonged hypocarbia and hypercarbia after experimental global ischemia in cats.

Hyperventilation therapy is often recommended after an episode of global cerebral ischemia (cardiac arrest), even though several workers have shown that under such circumstances the cerebral vasculature is unresponsive to changing PaCO2. However, no study has examined the effects of prolonged PaCO2 changes. We therefore studied the cerebrovascular effects of a 3-h period of continuous hypercarbia (40 to 45 torr) or hypocarbia (15 to 20 torr) in cats resuscitated from 12 min of electrically induced ventricular fibrillation. There were no differences in postresuscitation cerebral blood flow (CBF) or EEG, but intracranial pressure was lower in the hypocapnic animals. Furthermore, hypocapnic cats retained some CBF responsiveness to varying PaCO2 levels, while no such response was noted in previously hypercapnic animals. These findings suggest that some measurable changes in postarrest cerebrovascular behavior can result from prolonged hypocapnia (possibly related to tissue pH alterations). Whether such changes will have clinical utility is unclear.

Animals↗

Cerebral effects of isovolemic hemodilution with a hypertonic saline solution.

In view of a growing interest in the resuscitative use of hypertonic saline solutions, the authors have examined the cerebral effects of isovolemic hemodilution carried out over 1 hour (hematocrit decreased from 40% to 20%, stable arterial and right arterial pressures), using a hypertonic lactated Ringer's solution (HT-LR: Na+ 252 mEq/liter, osmolality 480 mOsm/liter). Experiments were carried out in anesthetized ventilated rabbits. Measured variables included cerebral blood flow (using the H2 clearance method), intracranial pressure (ICP), the electroencephalogram, spinal cord and skeletal muscle water content (%H2O), and the specific gravity of small (10- to 30-mg) tissue samples taken from different areas of the left hemisphere (including the cortex, thalamus, internal capsule, and hippocampus). The changes produced by HT-LR were compared with those seen in both undiluted control animals and in rabbits hemodiluted with normal saline (Na+ 155 mEq/liter, osmolality 310 mOsm/liter). The results demonstrate that hemodilution with HT-LR leads to the expected increases in serum Na+ and osmolality (158 +/- 6 mEq/liter and 320 +/- 5 mOsm/kg, respectively, mean +/- standard deviation) and that these were accompanied by reductions in the %H2O of all cerebral and extracerebral tissues, increases in the specific gravity of all tissue regions studied, and a decrease in ICP (1.9 +/- 0.7 mm Hg). By contrast, rabbits with hemodilution by normal saline showed no changes in either %H2O or specific gravity, but had significant increases in ICP (3.3 +/- 1.3 mm Hg). Cerebral blood flow increased in all animals hemodiluted with either HT-LR or normal saline by a combined average of +29 ml/100 gm/min. Although these studies were performed in neurologically normal animals, the combination of cerebral changes seen with HT-LR (cerebral dehydration, less peripheral edema, decreased ICP but with increased cerebral blood flow) suggests that this approach may have some advantages over the use of isotonic fluids, and may have some utility in the resuscitation of head-injured patients.

Animals↗

The hemodynamic consequences of high-dose thiopental anesthesia.

The hemodynamic and electroencephalographic effects of a 60 min infusion of thiopental, given at the rate of 1.25 mg X kg-1 X min-1 (total dose 75 mg/kg), were studied in 10 patients without cardiorespiratory disease undergoing surgery for the removal of large and/or deeply seated arteriovenous malformations. Data on heart rate, arterial, right atrial, pulmonary arterial, and pulmonary capillary wedge pressures, thermodilution cardiac output (expressed as cardiac index), the electroencephalogram, arterial blood gases, and serum thiopental concentrations were collected during a sedated, resting control period, and then every 15 min during drug infusion. Lactated Ringer's solution (total volume 1-2 liters) was infused throughout the study period at rates sufficient to maintain pulmonary capillary wedge pressure at control values. In doses sufficient to render the electroencephalogram isoelectric [t approximately equal to 30 min, 37.5 mg/kg cumulative dose, serum concentration 51 +/- 17 micrograms/ml (mean +/- SD)], drug infusion resulted in significant increases in heart rate (to 116% of control), and decreases in arterial pressure (to 87% of control), stroke volume index (to 87% of control), systemic resistance (84% of control), and both left and right ventricular stroke work indices (66% and 69% of control, respectively). Cardiac index was unchanged (following a transient increase at t = 15 min). There were no changes in pulmonary vascular resistance, or blood gases. A large total dose of thiopental (8-11 gm) was needed to maintain electroencephalogram suppression for the remainder of these 10-20 hr procedures, and emergence was slow (48-72 hr). The resultant prolonged ICU support may have contributed to serious postoperative complications in two patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

A comparison of the cerebrovascular and metabolic effects of halothane and isoflurane in the cat.

Halothane is a well known cerebral vasodilator that can produce dangerous increases in intracranial pressure (ICP) in certain neurosurgical patients. It has been suggested that isoflurane may be a less potent cerebral vasodilator. The authors therefore undertook a direct comparison of the effects of halothane and isoflurane on cerebral blood flow (CBF), cerebral vascular resistance (CVR), intracranial pressure, and cerebral metabolic rate for oxygen (CMRO2). Studies were carried out in normocarbic mechanically ventilated cats, using the intracarotid 133Xe injection technique to measure CBF. The effects of three doses were examined: 0.5, 1.0, and 1.5 MAC, studied in the continued presence of 75% N2O. Autoregulation also was tested at 1.0 MAC (plus 75% N2O) by recording CBF and CVR before and after elevation of blood pressure with angiotensin. Both agents had similar effects on blood pressure and ICP. However, while halothane produced significant increases in CBF at all doses, with values of 61 +/- 5 ml X 100 g-1 X min-1 (123 +/- 8% of control, mean +/- SE) at 1.0 MAC, isoflurane anesthesia caused no significant changes in CBF at any level, (e.g., 48 +/- 8 ml X 100 g-1 X min-1 or 94 +/- 12% of control at 1.0 MAC). Both drugs produced dose-related decreases in CVR, but the changes were greater with halothane, e.g., CVR at 1.0 MAC halothane = 1.46 +/- 0.20 mmHg X ml-1 X 100 g X min (47 +/- 7% of control) compared with 2.23 +/- 0.40 mmHg X ml-1 X 100 g X min (72 +/- 9% of control).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The hemodynamic consequences of high-dose methohexital anesthesia in humans.

The hemodynamic, electroencephalographic (EEG), and metabolic effects of a high-dose methohexital anesthetic were examined in eight neurosurgical patients. The patients were studied at rest and at 15-min intervals during a 60-min infusion of the drug, given at a rate of 0.40 mg . kg-1 . min-1 (total dose 24 mg/kg). Ventilation was controlled with oxygen:air (FIO2 = 0.50), and fluid was infused at a rate sufficient to maintain pulmonary capillary wedge (PCW) pressures at control values (8 +/- 2 mmHg, mean +/- SD). Serum methohexital concentrations increased progressively, reaching values of 11.7 +/- 2.9 micrograms/ml at t = 30 min and 18.1 +/- 10.8 micrograms/ml at t = 60 min. Characteristic barbiturate-induced EEG changes were noted, with isoelectricity achieved at t = 28 +/- 13 min. Methohexital infusion resulted in significant reductions in arterial pressure (84% of control at t = 60 min), systemic vascular resistances (83% of control at t = 60 min), right and left ventricular stroke work indices (65% and 68% of control, respectively at t = 60 min), and total body O2 consumption (76% of control at t = 60 min). In addition, a progressive dose-related decrease in stroke volume index was noted (50.1 +/- 90 ml X beat-1 X m-2 at t = 0, 40.1 +/- 10.2 ml X beat-1 X m-2 at t = 60 [80% of control]). This occurred in spite of unchanged ventricular filling pressures.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Minimal alveolar concentrations for halothane, enflurane, and isoflurane in the cat.

The minimal alveolar concentrations for halothane, enflurane, and isoflurane in the domestic cat were found to be 1.19 +/- 0.05 (SEM)%, 2.37 +/- 0.06%, and 1.61 +/- 0.04%, respectively. During the potency studies, it was observed that enflurane and isoflurane resulted in shorter wake-up times, compared with halothane. However, enflurane and isoflurane produced electroencephalographic (EEG) and clinical signs of CNS irritability (EEG spiking, myoclonus) in normocapnic or mildly hypocapnic cats. In addition, enflurane and isoflurane caused greater airway irritability (coughing, salivation) than did halothane.

Anesthesia, Inhalation↗

Cerebral blood flow during high frequency ventilation in cats.

Cerebral blood flow (CBF) was compared during conventional low frequency ventilation (LFV) [tidal volume 15 ml/kg, respiratory rate 12] and high frequency ventilation (HFV) [tidal volume 3 ml/kg, respiratory rate 100] in normal cats. The intra-arterial 133Xenon technique was used to determine CBF. No significant difference in CBF was present between the 2 groups. The mean CBF was 46.6 +/- 14.2 ml/dl X min during LFV and 44.4 +/- 12.2 ml/dl X min during HFV. Additionally, mean arterial pressure, CVP, intracranial pressure (ICP), cerebral perfusion and airway pressures were not significantly different between the groups. HFV has little effect on cerebral hemodynamics.

Animals↗

The neurologic effects of thiopental therapy following experimental cardiac arrest in cats.

To define the utility of high-dose barbiturate therapy following an episode of complete global cerebral ischemia, we investigate the effects of 60 mg/kg of thiopental given to cats five minutes after resuscitation from 12, 14, or 16 min of electrically induced ventricular fibrillation (VF). All aspects of the arrest, resuscitation, with post-arrest care were carefully controlled, with the EEG becoming isoelectric 20-25 s after the onset mean resuscitation time of 2.5 +/- 0.2 (SEM) min. For any given duration of VF, there were no differences (control vs thiopental) in any pre- or post-arrest parameters (blood pressure, blood gases, electrolytes, etc.) A total of 68 resuscitated cats were entered into various treatment and control groups, and all but one group received 20-24 h of post-resuscitation paralysis, mechanical ventilation, and ICU support before being extubated. Cats received an additional six days of aggressive nursing care, and daily examinations were performed with the assignment of a neurologic deficit score (NDS) between 0 (normal) and (brain dead). Autopsies were performed to determine the cause of death in animals which died before the end of the seven-day observation period. The early post-arrest period was marked by the occurrence of repetitive, rhythmic bursts of high-frequency electroencephalographic (EEG) activity (? seizures) in 38 per cent of control animals (16/42, all arrest times combined). Ten of these animals died as a result of severe neurologic injuries. By contrast, only 12 per cent of treated cats (3/26) developed similar EEG patterns (P less than 0.05) and there were no neurologic deaths in the thiopental groups. The differences in the incidence of neurologic deaths (control vs. thiopental) was significant (P less than 0.02). The change in overall mortality did not quite reach significance (36 per cent vs. 21 per cent), and treatment had no effect on the incidence of deaths due to cardiovascular causes (e.g., myocardial infarctions). In spite of the effects on mortality, treatment had no effect on the neurologic function of survivors (assessed by NDS). These findings suggest that thiopental improved survival rates by suppressing an unusual post-arrest EEG pattern (? anticonvulsant effect), but had no additional cerebral protective effects.

Animals↗