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PubMed1979

Differentiation of normal pressure hydrocephalus and cerebral atrophy by computed tomography and spinal infusion test.

The diagnostic value of computed tomography (CT) and spinal infusion test (SIT) was investigated in 27 patients with normal pressure hydrocephalus (NPH) and 35 patients with cerebral atrophy. The most consistent CT finding of NPH was dilatation of the temporal horns, that of cerebral atrophy widening of the convexity sulci. However, 43% of patients with cerebral atrophy demonstrated no cortical atrophy. The SIT showed an excellent relation with isotope cisternography and continuous intracranial pressure recording. NPH and cerebral atrophy were correctly differentiated in 71% by CT and SIT. A normal SIT and a CT scan without the typical features of NPH exclude impairment of cerebrospinal fluid absorption. An abnormal SIT and a CT scan showing ventricular enlargement without dilatation of convexity sulci, require isotope cisternography and possibly intracranial pressure recording to determine the degree of the absorption deficit.

Atrophy↗

PubMed1976

Reflex sympathetic tachycardia during intravenous infusions in chronic spinal cats.

The reflex tachycardia elicited by rapid intravenous infusions of a blood substitute was studied in 21 chronic cats with spinal sections at C8. All animals could breath spontaneously. The day after section the average resting heart rate (HR) and arterial pressure (AP) were 109 beats/min and 98/67 mmHg, respectively. Vagal blockade with atropine (0.5-0.7 mg/kg iv) was performed prior to each infusion, increasing the average HR To 127 beats/min. In 39 infusions in 21 cats the average increase in HR was 10 beats/min (range from -6 to +22 beats/min). A tachycardia was observed in all but five trials, four of which were obtained in two cats that subsequently responded with a tachycardia. In seven animals the neural circuit mediating the response was partially or totally interrupted by section of several thoracic dorsal roots (T1-T4 or T1-T6) and of the spinal cord at the inferior level of these sections (between T6 and T7). The tachycardia response was progressively reduced and finally abolished by these procedures. These experiments indicate that spinal neural mechanisms are likely to contribute to the phenomenon first described by Bainbridge.

Animals↗

PubMed1976

[Clinical observations on hydrocephalus with special regard to the posttraumatic malresorptive form (author's transl)].

100 cases of Spitz-Holter shunts performed for hydrocephalus over a period of 3 years were analyzed; 17 of these were of posttraumatic origin and are discussed in regard to pathogenesis, clinical symptoms, diagnostic methods, and therapy. Half of these 17 had severe traffic accidents. The rapidity and degree of ventricular dilatation were positively correlated with the duration of unconsciousness. When the unconsciousness had lasted more than 10 days hydrocephalus was recognized early, and the shunt was performed on an average 2 months after the trauma. Two thirds of the patients improved after the shunt operation. Pathogenetically we believe the important factors in the acute stages are increased CSF pressure, disturbed CSF dynamics, brain swelling and vascular circulation disorder; in the chronic stages, parenchymous atrophy. The following 3 types of posttraumatic hydrocephalus were differentiated on the basis of the clinical features: --symmetrical communicating internal hydrocephalus with malresorption, especially after subarachnoid hemorrhage, --communicating internal hydrocephalus alone, or in combination with external hydrocephalus resulting from atrophy, --internal occlusive hydrocephalus after trauma. The following posttraumatic clinical features were found to be indications that hydrocephalus may be present: in the acute stages inadequately long symptom resolution considering the severity of the trauma, secondary changes for the worse, an apallic syndrome which does not improve; in late stages, the presence of an Adams-Hakim syndrome charaterized by dementia, a spastic gait and loss of sphincter control. The most successful diagnostic methods were found to be pneumencephalography with 24 and 48 h delayed exposures, cisternoscintigraphy and continuous intracranial pressure monitoring in combination with the spinal infusion test. The most important intracranial shunting procedures and the indications for shunting are discussed.

Accidents, Traffic↗

PubMed1976

[Pressor action of propranolol; with special reference to relationship between the pressor action and peripheral vascular tone].

We showed in previous studies that pro pranolol produced a pressor action in the rat, and that this action was also observed in the spinal rat infused with adrenaline, noradrenaline and a mixture of isoproterenol and vasopressin, but not with vasopression alone. The action was also observed in the guinea pig infused with adrenergic beta-stimulants. In the present work, conditions in the peripheral vessels in which propranolol observed in the spinal rat infused with a mixture of various doses of isoproterenol and vasopressin. The effect of propranolol on the blood pressure in guinea pigs and rabbits with a reduced vasoconstrictive tone in the peripheral vascular beds with alpha-blockade was studied. Propranolol produced a pressor action in the spinal rat infused with a mixture of isoproterenol and vasopressin, and the magnitude of the rise depended on the mixing rate of the doses of these two drugs. The drug also produced a sustained rise in blood pressure in guinea pigs and rabbits treated with alpha-blockers. Thus, it is concluded that propranolol produces a marked pressor action when peripheral vessels are maintained in conditions with an appropriate constrictive and beta-adrenoceptive vasodilator tone.

Adrenergic alpha-Antagonists↗

PubMed1979

Effect of dopamine on hypotension induced by spinal anesthesia.

Chronically instrumented, near-term pregnant sheep were subjected to autonomic blockade with spinal anesthesia. Systemic arterial pressure, heart rate, and uterine blood flow decreased and uterine vascular resistance increased during the spinal blockade. Infusion of dopamine during the spinal hypotension corrected the disturbed circulatory parameters. These data provide evidence that: (1) the peripheral circulation of the near-term pregnant sheep is as sensitive as that of pregnant women to autonomic blockade, (2) the sensitivity is probably related to factors other than the changes in venous pressure in areas below the pelvis, and (3) dopamine represents a useful agent in the management of spinal hypotension.

Anesthesia, Spinal↗

PubMed1975

Effects of several beta-blockers on blood pressure in the rat.

Effects of practolol, alprenolol and pindolol on blood pressure in the rat were studied. Also effects of these three beta-blocking agents on blood pressure and heart rate in spinal rats during adrenaline infusion were studied and compared with those of propranolol. The beta-blocking agents produced a sustained pressor action in the rat, and in the spinal rat infused with adrenaline. The magnitude of the pressor action induced by the beta-blockers was in the following order: pindolol larger than or equal to propranolol larger than or equal to alprenolol greater than practolol. Minimum doses of these beta-blockers required to cause a pressor action in the spinal rat infused with adrenaline were in the following order; practolol greater than alprenolol larger than or equal to propranolol larger than or equal to pindolol. The magnitude of the pressor action produced by the same dose of these beta-blockers and minimum doses of these beta-blockers required to cause a pressor action in the spinal rat infused with adrenaline seemed to be roughly proportional to their beta-receptor blocking activities. It was concluded that the minimum doses of these beta-blockers required to cause a pressor action and the magnitude of the pressor action induced by the beta-blockers in the spinal rat infused with adrenaline could be used to compare their beta-blocking activities and that practolol, a cardioselective beta-blocker, seems to block not only cardiac beta-receptor but to some extent also peripheral vascular beta-receptors.

Adrenergic beta-Antagonists↗

PubMed2026

Comparison of a Modified Regimen of Prophylactic Phenylephrine Boluses Versus Variable Rate Infusion During Elective Cesarean Delivery Under Spinal Anesthesia: A Noninferiority Randomized Double-Blind Study.

BACKGROUND: Prophylactic phenylephrine boluses have been found to be as effective as variable rate infusions during elective cesarean delivery but require a higher number of physician interventions to maintain blood pressure near baseline values. Therefore, there is a need to find a feasible regimen of bolus administration that is equally efficacious to the infusion regimen while at the same time requires a comparable number of physician interventions and is thus non-inferior to the infusion regimen. METHODS: Healthy pregnant women with term, uncomplicated, singleton pregnancies undergoing elective cesarean delivery under spinal anesthesia were randomly divided into two groups. The Bolus group received a phenylephrine bolus 100 μg immediately after spinal anesthesia and then at every systolic blood pressure value <90% of the baseline. The infusion group received a prophylactic variable-rate infusion of phenylephrine beginning at 50 μg/min and titrated to maintain systolic blood pressure at 90-99% of baseline. The primary outcome was the number of physician interventions needed to maintain the target systolic blood pressure; the secondary outcomes included phenylephrine requirements, incidence of hypotension/hypertension/bradycardia, umbilical arterial and venous blood gas analysis, Apgar scores, and maternal complications. The primary outcome was analyzed in terms of non-inferiority using a non-inferiority margin of two interventions. RESULTS: Eighty patients were included in the study. The median (interquartile range [IQR]) number of physician interventions was 6 (5-8) in the infusion group and 3 (2-4) in the bolus group (P < .001). The difference of medians (95% confidence interval [CI]) between the two groups was -3 (-4 to -2). Phenylephrine requirements were higher in the infusion group (630 [426-765] μg) compared to the bolus group (300 [200-400] μg; P < .001). Blood pressure was higher at certain time points in the infusion group, but overall accuracy of blood pressure control was not different between the groups. Incidence of hypotension, hypertension, and bradycardia, neonatal outcomes, and maternal complications did not differ between the groups. CONCLUSIONS: The modified regimen of prophylactic boluses is non-inferior to variable rate prophylactic phenylephrine infusion in terms of physician interventions needed to maintain systolic blood pressure within the target range and maternal and neonatal outcomes.

Humans↗

PubMedDate not supplied

Regression pattern of amplitude of electrocardiographic waves during intravenous infusion in intact, buffer nerve denervated and spinal dogs.

Electrocardiographic (ECG) amplitude changes during clinically feasible rate of infusion of normal saline (NS), Ringer-Locke (RL) solution and tender coconut water (TCW) upto a dose of 100 ml/kg in paraldehyde (PLD) and chloralose and urethane (C&U) anaesthetised dogs were studied. The infusion caused a net decrease in P and QRS amplitudes but had varied effect on T wave amplitude in intact PLD and C&U anaesthetised dogs. Infusion of RL in vagotomised and/or carotid sinus (CS) denervated dogs and in spinal dogs indicated that these neural pathways had a significant effect on basal amplitude of ECG waves but their influence on infusion induced ECG changes was only marginal; in this the vagi seem to have a greater influence than the other pathways. The T wave changes during infusion were independent of simultaneous P and QRS changes and appeared to depend on the ionic composition of the infusion fluid. TCW infusion was very well tolerated, particularly by the C&U anaesthetised dogs. It would seem that the evaluation of ECG from patients on parenteral fluid be done in the context of the present observation that infusion per se decreases the amplitude of ECG.

Animals↗

PubMed1975

Spinal autonomic afferents in elicitation of tachycardia in volume infusion in the dog.

Intravenous infusion of blood (36 ml/kg body wt) elicited tachycardia in artificially ventilated anesthetized dogs with intact autonomic innervation and in dogs with cardiac beta-receptor blockade. In contrast, infusion elicited bradycardia in dogs with section of the spinal cord at C6-C7, and in dogs with combined spinal section and cardiac beta-receptor blockade. The control heart rate was less than or equal to 110 beats/min in all the animals. The presence of infusion-induced tachycardia in dogs with beta-receptor blockade, i.e., dogs in which cardiac sympathetic efferents were blocked, and its absence in dogs with combined spinal section and beta-receptor blockade, i.e., dogs in which spinal autonomic afferents plus cardiac sympathetic efferents were blocked, may be the result of an additional interruption of spinal autonomic afferents by spinal section. It is concluded that tachycardia elicited by infusion may be partly due to a reflex with its afferent pathway in the spinal cord and its efferent pathway in the vagus nerves.

Afferent Pathways↗

PubMed1978

Cardiovascular actions of optical isomers of propranolol.

Effects of the optical isomers of propranolol on blood pressure in the rat, and in the spinal rat during adrenaline infusion were studied to investigate the mechanism of the pressor action of propranolol. Both isomers of propranolol produced a sustained pressor action in the rat and in the spinal rat infused with adrenaline. The magnitude of the pressor action produced by the d- and 1-propranolol was proportional to their beta-adrenoceptor blocking activities in the heart as was reported by several investigators. It is concluded that the pressor action of propranolol is due to the blockade of the beta-adrenoceptors mediating vasodilation in the skeletal muscle vascular beds.

Adrenergic beta-Antagonists↗

PubMed1979

Clearance of macromolecular and particulate substances from the cerebrospinal fluid system of the rat.

Arachnoid villi in the intracranial dural sinuses constitute the principal sites for absorption of proteins and particulates from the cerebrospinal fluid (CSF) system. Although arachnoid villi in the rat are morphologically less complex than those found in other mammals, their resistance to CSF outflow, as assessed by a graded series of contstant flow manometric infusions, is similar to that found in other species. Moreover, inulin and polystyrene beads, when infused into the spinal subarachnoid space of rats, are rapidly cleared from the CSF system into intracranial dural sinuses. Inulin appeared in sinus blood 3 minutes after onset of infusion and reached concentrations 26 times greater than those found in the systemic circulation; particulate matter in the form of 0.5 micrometer polystyrene beads showed similar efflux characteristics. Hence, the CSF system of the rat is functionally similar to that found in other mammalian species, with arachnoid villi constituting a major efflux route for clearance of macromolecular and particulate substances.

Absorption↗

PubMed1979

Stimulation of phrenic nerve activity by salicylate.

To assess the possibility that salicylate stimulates VE by direct excitation of phrenic motoneurons, we compared two groups of anesthetized vagotomized dogs with respect to increases in phrenic nerve activity elicited by a large dose of sodium salicylate (225 mg/kg). The sole difference between the two groups of animals was the condition of the spinal cord (SC); SC remained intact in one group of animals (i.e., intact animals) whereas the other group of animals (i.e., T1 spinal-transected animals) underwent complete transection of the SC at the first thoracic level. Both groups of animals were ventilated by a respirator and arterial PCO2 was maintained constant throughout all experiments. Following salicylate infusion, intact animals exhibited two- to threefold increases in the frequency of phrenic nerve bursts and three- to fivefold increases in moving average minute phrenic activity (i.e., the summation of peak integrated burst activity per minute). In contrast, salicylate infusion into T1 spinal-transected animals elicited no statistically significant increase in the frequency of phrenic nerve bursts while increases in minute phrenic activity were limited to 32 +/- 8%. Since T1 spinal transection markedly diminishes increases in phrenic nerve activity elicited by salicylate, we conclude that salicylate stimulates VE by a reflex mechanism whose afferent pathways originate in metameres below T1.

Action Potentials↗

PubMed1979

Pentolinium for control of reflex hypertension in spinal cord injured patients.

Ganglioplegia was produced by intravenous infusion of pentolinium tartrate 5 mg to control reflex hypertension in 29 patients with chronic spinal cord injuries undergoing 32 elective surgical procedures. The patient group with lesions above the first thoracic segment (T1) demonstrated significant but moderate intraoperative elevation of both systolic and diastolic pressure whether pentolinium was given prior to or during surgical stimulation. Patients with lesions below T1 had no significant pressure elevations with either mode of therapy. Pentolinium ganglioplegia can safely maintain blood pressure within reasonable limits in these patients; some increase in dosage may be required in patients with lesions above T1.

Adolescent↗

PubMed1975

Sympathetic component of the pressor response to angiotensin II in the pithed rat after pretreatment with disulfiram.

Pressor responses to angiotensin II in the pithed rat were unaffected or slightly increased by procedures such as reserpine pretreatment, alpha and beta adrenoceptor blocking agents or bethanidine which inhibit the sympathetic system. Disulfiram-induced inhibition of angiotensin II pressor responses was unaffected by pretreatment with either alpha-adrenoceptor blockers or bethanidine. Pretreatment with disulfiram prevented infusions of angiotensin II from increasing the responses to spinal sympathetic outflow stimulation. After inhibition of pressor responses to angiotensin II by disulfiram the responses were restored by infusions of noradrenaline, or alpha-methyldopa. The restored responses, unlike control responses, were inhibited by phentolamine. The results suggest that angiotensin II facilitates neuronal release of noradrenaline and that this effect is revealed most clearly when post-synaptic angiotensin II receptors are blocked.

Adrenergic alpha-Antagonists↗

PubMed2026

Continuous Intrathecal Infusion of Nivolumab in Advanced Melanoma With Concomitant Leptomeningeal Disease: Efficacy, Safety, and Pharmacokinetics.

BACKGROUND AND OBJECTIVES: Prognosis of melanoma with leptomeningeal disease (LMD) is poor (median overall survival of 5.1 months). Intrathecal (IT) nivolumab appears safe, although its efficacy remains uncertain. We investigated the feasibility, safety, and efficacy of continuous IT nivolumab. METHODS: This was a retrospective analysis of 11 melanoma patients with progressive LMD (MelBase; NCT02828202) treated as part of the patients' care with continuous IT nivolumab administered through spinal (n = 10) or ventricular catheter (n = 1). RESULTS: Patients (5 women, median age 52) with Eastern Cooperative Oncology Group ≤1 (except for 1) and stable extracranial disease (except for 4) were treated over a median duration of 1.5 months and followed for 2.5 months. Seven presented symptomatic LMD. Primary tumors were mostly cutaneous (n = 8) and BRAF-mutated (n = 10). All patients had progressed on systemic immunotherapy; 7 had received brain radiotherapy (whole brain radiotherapy [n = 3]; stereotactic radiosurgery [n = 4]). Concomitant therapies included corticosteroids >10 mg (n = 5), intravenous nivolumab (first 3 months of IT therapy, n = 1), and targeted therapies (n = 7). The median overall survival was 2.5 months, with 3 patients surviving for more than a year. Reversible treatment-related adverse events occurred in 5 patients: meningoencephalitis (grade 3, n = 1), intracranial hemorrhage (grade 1, n = 1), intracranial hypotension (grade 2, n = 2; grade 1, n = 1). Baseline levels of nivolumab in the cerebrospinal fluid (CSF) were <2 µg/mL, even among patients with plasma detection. CSF concentrations of nivolumab at steady state varied from 36 to 97 µg/mL, with clearances of 4.3-15.7 mL/h. Next-generation sequencing identified CSF genomic profiles correlating with clinical progression in 4 patients. CONCLUSION: These findings warrant further trials on IT nivolumab.

Humans↗

PubMed1979

Anterior spinal artery syndrome--a complication of cervical intrathecal phenol injection.

Spinal nerve block by intrathecal phenol-glycerine infusion is commonly employed for relief of severe pain in terminal carcinomatosis and, frequently, a dramatic regional anesthetic effect is achieved. However, nerve block by this procedure may in very rare instances give rise to serious complications. We have seen a case of terminal malignant melanoma in which clinical manifestations, indicative of anterior spinal artery syndrome, developed following the injection of 0.3 ml of 10% phenol-glycerine into the cervical subarachnoid space at the C4--C5 level for the control of severe right arm pain. This report describes the clinical course of the patient over a period of 4 months after the nerve block and the post-mortem findings along with a brief review of the literature.

Adult↗

PubMed1979

Continuous mini-infusion of bupivacaine into the epidural space during labor. Part I: Radiographic visualization of the epidural catheters.

Two groups, each consisting of 20 parturients, were given a continuous infusion of 0.25 per cent bupivacaine into the epidural space for pain relief, after test and loading doses. The analgesic effect was registered during labor. After delivery the course of the catheters in the epidural space was investigated radiologically. In the first group long catheters (mean 16.5 cm from the skin surface) and in the second group short catheters (mean 10.5 cm) were used. The medial approach in the epidural space was varied between the first and second lumbar interspaces. The relationship between the position of the catheter tip and the degree of analgesia was also studied. In two mothers with fetus mortuus ante partum, the spread of a radiopaque dye solution was followed during labor. Through the force of gravity and the mothers position, the spread of solution covered three segments within 30 minutes. It was concluded, that slow infusion of local anesthetic solution gives satisfactory pain relief if the catheter is inserted into the first lumbar interspace to a depth of 10--12 cm from the skin surface ending close to the Th12 level. Gradual raising of the mother from the supine to the semirecumbent position and regular change of sides during mini-infusion is important for an even spread of the analgesic solution and analgasia.

Anesthesia, Epidural↗

PubMed1979

Use of metrizamide computerized tomographic cisternography in the evaluation of patients with malignant glioma for immunotherapy.

The communication between the subarachnoid space and the surgically created tumor cavity in glioma patients was evaluated by metrizamide cisternography. It was necessary to know the presence or absence of such a communication to determine the route of administration of autologous lymphocytes as a form of immunotherapy. The contrast injections were made either into the spinal subarachnoid space or directly into the tumor cavity. The presence of communication was demonstrated and followed by computerized tomographic (CT) scanning. The results were also corroborated by comparing the white cell counts in the fluid from the tumor cavity and the spinal subarachnoid space 24 hours after autologous lymphoid cell infusion. In only two of seven patients was a communication present. In the five patients without a communication, the blocks were at the tentorial hiatus (one patient), due to a nonpatent subarachnoid space over the cerebral convexity (two patients), and the result of adhesions at the pial margin of the tumor cavity (three patients). In addition, certain limitations in the use of computerized tomography in the evaluation of glioma patients are demonstrated. These problems include the effects of steroids on tumor size, the poor correlation between "enhancement" on CT scan and tumor recurrence, and the difficulty of differentiating metrizamide and hemorrhage by CT scan in the immediate postoperative period. (Neurosurgery, 5: 576--582, 1979).

Adult↗