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PubMed1992

Treatment of stress response during balanced anesthesia. Comparative effects of isoflurane, alfentanil, and trimethaphan.

Acute hypertensive responses during nitrous oxide-opioid-relaxant anesthesia are a common clinical problem. In adult men undergoing radical prostatectomy procedures and anesthetized with a standardized technique, we evaluated the effectiveness of alfentanil, isoflurane, and trimethaphan in treating acute hemodynamic and stress hormone responses to surgical stimulation. Stress hormone concentrations were measured 1 min before skin incision, after the onset of an acute hypertensive response, and after returning the mean arterial pressure to within 10% of the preincision values with one of the three treatment modalities. Pretreatment plasma alfentanil concentrations (151 +/- 47 to 156 +/- 47 ng.ml-1) and end-tidal nitrous oxide concentrations (66 +/- 2 to 68 +/- 2%) were similar in all three groups. Acute hypertensive events were associated with significantly increased concentrations of catecholamines and vasopressin (antidiuretic hormone [ADH]). Whereas intravenous alfentanil returned all hormone concentrations to preincision values, norepinephrine and glucose concentrations were significantly increased after adjunctive isoflurane administration. Although trimethaphan decreased the norepinephrine concentration, the epinephrine, beta-endorphin, cortisol, ADH, and glucose concentrations were significantly increased compared to preincision values. However, the persistent elevation in the posttreatment ADH concentration in the trimethaphan group was the only significant difference between the three groups. Mean (+/- standard deviation) times to awakening (2.8 +/- 3.3 to 3.8 +/- 4.2 min), extubation (8.1 +/- 4.8 to 10.3 +/- 8.5 min), and orientation (19.6 +/- 20.4 to 24.6 +/- 19.1 min) were similar in all three groups. Naloxone was required more frequently in patients in the alfentanil (35%) and isoflurane (24%) groups than in the trimethaphan group (4%).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1996

Ultra-high dose trimethaphan in an infant with severe hypertension.

BACKGROUND: Trimethaphan camsylate is a potent antihypertensive drug used to induce systemic arterial hypotension in patients undergoing major surgery and to treat severe systemic hypertension. The pharmacokinetics and pharmacodynamics of trimethaphan administered in the usual clinical dosages have been previously reported. The effects of trimethaphan when administered in very high doses of 500-1000 times the usual dose have not been reported. CASE REPORT: A case is presented of an infant with severe hypertension who inadvertently received such an overdose of trimethaphan.

Antihypertensive Agents↗
PubMed1992

[Effects of hypotensive anesthesia with prostaglandin E1 or trimethaphan on renal microstructure].

A study was made on the presence or absence and the degree of histopathological renal cell damage, in hypotensive anesthesia models with prostaglandin E1 (PGE1) or trimethaphan. Cell damage was most noticeable in the S3 segment, the straight and second half part of the proximal renal tubule. The lesion was evaluated and semiquantified. The trimethaphan group in this area exhibited degeneration--including cell vacuolation and granule increase in this site, as well as cytoclasis such as cell fragments in the lumen, luminal extension, flattening of epithelial cell and damage of distal renal tubular columns. In the PGE1 group, cell degeneration was milder than in the trimethaphan group, and there were no cytoclasis findings. Renal cell damage in the PGE1 group was slighter than in the trimethaphan group.

Alprostadil↗
PubMed1976

Changes in serum potassium and blood glucose concentrations after trimethaphan administration in man.

Blood glucose and serum potassium (K+) concentrations were measured before, during, and 60 minutes after operation in two groups of 10 patients during nitrous oxide/halothane/d-tubocurarine anesthesia for major orthopedic surgery. In the control group, arterial blood pressure was maintained within normal range, while in the study group trimethaphan camsylate was administered as an intravenous infusion (average, 218 mg.) to maintain a systolic blood pressure of 60 to 65 torr. In the normotensive group, blood glucose rose significantly during operation and early postoperatively and serum K+ was essentially unchanged. In the hypotensive group, trimethaphan caused a striking modification of surgically induced hyperglycemia, together with a small significant decrease in serum K+ intraoperatively. The observed increase in blood glucose is part of the autonomic response to surgical stress. Hormonal factors (growth hormone, cortisol and glucagon) may conceivably be involved. The decrease in serum K+ is probably caused by decreased hepatic glycogenolysis and attenuation of the suppressive effect of catecholamines on insulin release, both effects being secondary to the ganglionic blocking property of trimethaphan. These results indicate that trimethaphan, in contrast to other ganglionic blocking drugs, does not cause hypoglycemia and suggest that serum K+ concentration should be monitored whenever these drugs are used.

Adolescent↗
PubMed1986

The influence of trimethaphan (Arfonad)-induced hypotension with and without spine distraction on canine spinal cord blood flow.

Controlled hypotension is used in scoliosis surgery to reduce the need for transfusion and to improve operating conditions, but there is concern that deliberate hypotension may decrease spinal cord blood flow (SCBF) and predispose the spinal cord to injury, particularly when it is distracted during Harrington instrumentation. To study the effect of deliberate hypotension on SCBF, the mean arterial pressure (MAP) was reduced to 50% of its normotensive value with trimethaphan (Arfonad) in dogs and the SCBF measured using the hydrogen washout technique with and without spine distraction. The SCBF was significantly reduced to half its normotensive value of 23.2 ml/min/100 gm to 11.4 ml/min/100 gm after hypotension was established. The SCBF remained significantly decreased compared with controls when measured at 30, 45, and 60 minutes following the induction of hypotension and also when hypotension was terminated. SCBF was not further reduced when 2 cm of spine distraction was added. These results show that induction of hypotension with trimethaphan is associated with a similar decrease in SCBF, which is maintained as long as the drug is used and that this effect continues after the drug is terminated and the MAP increases. Cautiously extrapolating these findings clinically would suggest that trimethaphan may not be the drug of choice for controlled hypotension during scoliosis surgery, despite its apparently favorable hemodynamic and hormonal responses.

Animals↗
PubMed1988

The effect of trimethaphan-induced hypotension on canine spinal cord blood flow. Measurement at different cord levels using radiolabelled microspheres.

Controlled hypotension which is used during scoliosis surgery to improve operating conditions and minimize transfusion requirements may decrease spinal cord blood flow (SCBF). Previous studies using hydrogen washout, an invasive technique, have shown that trimethaphan-induced hypotension is associated with a decrease in SCBF, whereas hypotension induced with sodium nitroprusside or nitroglycerin is not. To determine whether the decrease seen with trimethaphan represented a generalized rather than regional spinal cord phenomenon, SCBF was measured at three separate cord levels (T2-3, 7-8, L2-3) using a noninvasive radionuclide-labelled microsphere technique. When the mean arterial pressure was reduced by 50%, SCBF decreased 35 to 45% at all levels of the cord examined, and remained at this reduced level during the period of hypotension. The results confirm that trimethaphan-induced hypotension is associated with a significant reduction in SCBF and that this occurs throughout the spinal cord during the period of hypotension.

Animals↗
PubMedDate not supplied

Prolonged neuromuscular blockade associated with trimethaphan: a case report.

A case of prolonged neuromuscular blockade associated with the administration of trimethaphan to a neurosurgical patient aged 29 is believed to be the possible result of interaction between trimethaphan, a ganglionic-blocking drug, and muscle relaxant. This possibility should be kept in mind when the administration of trimethaphan is being considered.

Adult↗
PubMed1975

Comparative hemodynamic responses to chlorpromazine, nitroprusside, nitroglycerin, and trimethaphan immediately after open-heart operations.

The hemodynamic effects of intravenous chlorpormazine, nitroprusside, nitroglycerin, and trimethaphan camsylate were studied in 51 patients with high mean arterial pressures immediately after open-heart operations. Chlorpromazine was given by bolus intravenous injection to 24 patients (average dose 10.3 mg); nitroprusside (17 patients), nitroglycerin (8 patients), and trimethaphan (12 patients) were administered by constant intravenous infusion at average doses of 77 mug/min, 59 mug/min, and .097 mg/min, respectively. Measured or derived variables included right atrial pressure, pulmonary artery pressure, left atrial pressure, systemic arterial pressure, heart rate (HR), cardiac index (CI), stroke index (SI), stroke work index (SWI), and systemic vascular resistance index (SVRI). All four vasodilators significantly reduced systemic and intracardiac pressures and SWI (P less than 0.01). Associated changes in left ventricular pumping performance, however, differed importantly between groups. Chlorpromazine caused a significant rise (+19%) in HR with preservation of SI; thus, CI rose significantly (P less than 0.01). Only nitroprusside, however, resulted in enhancement of SI (P less than 0.05) at the lowered left atrial pressure; CI increased by 19% (P less than 0.01), HR rose minimally (6.5%), and calculated SVRI diminished 33% (P less than 0.01). Both nitroglycerin and trimethaphan caused decreases in SI and CI. These results indicate that in general, among the vasodilators studied, nitroprusside is associated with the most favorable hemodynamic responses in early postoperative cardiac surgical patients.

Blood Pressure↗
PubMed1976

Respiratory paralysis during treatment of hypertension with trimethaphan camsylate.

Four cases are reported in which respiratory arrest occured coincident with the intravenous administration of large doses of trimethaphan camsylate (Arfonad) to control hypertension. The mechanism of the respiratory depression is unknown, but it may have been related to a direct effect of trimethaphan on the respiratory center or to a curare-like effect of the drug. Close monitoring of ventilatory capacity should be maintained in all patients treated with trimethaphan.

Adult↗
PubMed1995

Use of C1300 neuroblastoma cells to evaluate the protective value of hexamethonium, trimethaphan, hemicholinium, and triethylcholine against diisopropyl phosphorofluoridate toxicity.

Our intent was to evaluate the C1300 neuroblastoma cell as an in vitro system for studying the mode of action and efficacy of drugs used to treat or prevent organophosphate intoxication. The anticholinergic drugs hexamethonium, trimethaphan, and hemocholinium and the triethylcholine and cholinesterase/reactivator 2-pyridine aldoxime methochloride (2-PAM) have been shown to be effective in preventing intoxication by diisopropyl phosphorofluoridate (also known as diisopropyl fluorophosphate, DFP) in vivo. We determined their efficacy in preventing cell death (as measured by trypan blue exclusion) of neuroblastoma cells alone or in combination. We also determined their efficacy in reversing the cytotoxic effects of DFP on cell DNA synthesis (as measured by [3H]-thymidine incorporation), cell RNA synthesis (as measured by [3H]uridine incorporation), and on cell protein synthesis (as measured by [3H]leucine incorporation). The maximal nontoxic doses of the drugs in vitro were determined. All anticholinergic agents studied reduced the cytotoxicity of DFP using one or more parameters. 2-PAM, the cholinesterase reactivator, enhanced the cytotoxicity of DFP on cultured cells at a high concentration (1 mg/mL) and reduced it at a lower concentration (0.3 mg/mL). All four anticholinergic agents were capable of enhancing the uptake of [3H]thymidine. Only hexamethonium and hemicholinium reversed DFP inhibition of DNA synthesis. RNA synthesis was not affected by any anticholinergic agent and no agent reversed DFP inhibition of RNA synthesis. Protein synthesis was enhanced by every anticholinergic agent except hemicholinium; the inhibition of protein synthesis by DFP was reversed by trimethaphan and triethylcholine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Differential microcirculation dynamics during deliberate hypotension induced by nicardipine, PGE1 and trimethaphan in rat mesentery.

The purpose of this study was to determine the arteriolar changes that occur in the microcirculation during deliberate hypotension and general anaesthesia and whether the changes depended on the drugs used to induce vasodilatation or on the degree of systemic blood pressure decrease. Changes in the vessel diameter and the velocity of red blood cells in the mesenteric arterioles of pentobarbitone-anaesthetized rats were observed using continuous biomicroscopy. Observations were made during deliberate moderate (BP 70 mmHg) or deep (BP 50 mmHg) hypotension by titration with nicardipine, prostaglandin E1 (PGE1) or trimethaphan. Then, the responses of arterioles to locally applied noradrenaline (1 microgram) were assessed. During moderate hypotension PGE1 decreased the arteriole diameter slightly (16.7 +/- 1.6 to 14.7 +/- 1.3 microns, P < 0.05), reduced the velocity of red blood cells considerably (1.98 +/- 0.2 to 1.03 +/- 0.4 mm.sec-1, P < 0.05) and increased the contractile response of arterioles to locally-applied noradrenaline. Nicardipine and trimethaphan had no effect on the microcirculation. During deep hypotension, all drugs decreased the diameter of the arterioles slightly but reduced the velocity of red blood cells considerably (P < 0.05). We conclude that the major change in the mesenteric arterioles during deliberate hypotension during general anaesthesia is a decrease in red blood cell velocity that is dependent on the drug used and the degree of blood pressure decrease.

Alprostadil↗
PubMed1991

Local cerebral blood flow with prostaglandin E1 or trimethaphan during cerebral aneurysm clip ligation.

This study was performed to examine changes in local cerebral blood flow during hypotensive anaesthesia with either prostaglandin E1 (PGE1) or trimethaphan (TMP). Local cerebral blood flow (LCBF), mean blood pressure (MBP), heart rate (HR), and hourly urine output (UO) were studied in 51 patients undergoing cerebral aneurysm surgery with neuroleptanalgesia (NLA). The incidence of vasospasm after aneurysm surgery, and outcome (Glasgow Outcome Scale) at discharge were evaluated. Measurements of LCBF were made using a thermal gradient blood flow meter. The dose of PGE1 or TMP was adjusted to maintain MBP at about 70 mmHg, and LCBF was studied during and after PGE1 or TMP administration. Hypotensive drugs were discontinued at the completion of aneurysm clipping. After starting PGE1 or TMP, MBP decreased immediately, but HR did not change in either group. The LCBF decreased 30 min after the start of TMP administration and increased immediately after its discontinuation, whereas PGE1 did not affect LCBF. Urine output increased during PGE1 administration but was unchanged during TMP. Neither drug affected surgical outcome or the incidence of vasospasm. These results suggest that PGE1 may be preferable to trimethaphan for hypotensive anaesthesia in cerebral aneurysm surgery because LCBF is maintained.

Adult↗
PubMed1986

Prophylactic action of hexamethonium, trimethaphan, and mecamylamine against diisopropyl fluorophosphate poisoning in mice.

Prophylactic Action of Hexamethonium, Trimethaphan, and Mecamylamine against Diisopropyl Fluorophosphate Poisoning in Mice. Chiou, G. C. Y., Chang, W. T. S., and Aimoto, T. (1986). Fund. Appl. Toxicol. 6, 35-43. Hexamethonium, trimethaphan, and mecamylamine are ganglionic blockers which can reduce acetylcholine (ACh) release presynaptically. All these agents are capable of protecting mice from diisopropyl fluorophosphate (DFP) intoxication by prolonging the latent period of death or by completely preventing death. Combinations of these agents with 2-pyridine aldoxime methochloride (2-PAM) (50 mg/kg) improved prophylactic action even further. These results indicate that reduction of ACh release presynaptically plus neutralization of organophosphates with 2-PAM could be an effective way to reduce mortality in patients exposed to organophosphorus poisons.

Animals↗
PubMed1999

Blockade of smoking satisfaction using the peripheral nicotinic antagonist trimethaphan.

The present study was conducted to investigate the role of peripheral nicotinic receptors in mediating the rewarding effects of cigarette smoking. Twelve cigarette smokers rated cigarettes after intravenous infusion of the short-acting peripheral nicotinic receptor antagonist trimethaphan and after placebo (saline) infusions. Subjects were blinded to the infusion and cigarette conditions. Cigarette conditions included subjects' usual brand of cigarette, denicotinized tobacco cigarettes, and nicotine-injected cigarettes that had a tar delivery equal to that of the denicotinized cigarettes but with an enhanced nicotine delivery equal to that of subjects' usual brands. The latter cigarettes were rated as extremely harsh due to the high nicotine/tar ratio. Trimethaphan significantly attenuated the airway sensations associated with nicotine, and eliminated the difference in smoking satisfaction between the usual brand of cigarette and the other two cigarettes. These findings suggest that nicotinic receptors on peripheral nerve endings in the respiratory tract modulate smoking satisfaction and may be important in the maintenance of cigarette addiction.

Adolescent↗
PubMedDate not supplied

The effects of sodium nitroprusside and trimethaphan camsylate on cerebral blood flow in rhesus monkeys.

Hemispheric cerebral blood flow was measured in the rhesus monkey before and after infusion of the hypotensive agents sodium nitroprusside and trimethaphan camsylate. The intracarotid injections of 133Xe was utilized, and flow was calculated by the "flow initial" technique. Cerebral blood flow did not change significantly with the administration of trimethaphan camsylate. However, with a small reduction in blood pressure (10.6%) during the administration of sodium nitroprusside, the cerebral blood flow fell significantly (15.4%).

Animals↗
PubMed1979

[The effects of halothane-, nitroprusside- and trimethaphan-induced hypotension on cerebral blood flow and intracranial pressure (author's transl)].

Arterial hypotension to about 50 mm Hg mean pressure was induced in anaesthetized and artificially ventilated dogs by halothane, nitroprusside, and trimethaphan to study their effects on cerebral blood flow and intracranial pressure during hypotension. During nitroprusside induced hypotension there was a 32% increase in cerebral blood flow above control and a marked decrease in cerebral arteriovenous oxygen content difference indicating luxury perfusion of the brain. Cerebral blood flow remained high even 30 min after termination of hypotension. During halothane and trimethaphan hypotension cerebral blood flow remained unchanged. In all groups epidural pressure did not change substantially during hypotension but increased during recovery from nitroprusside hypotension by a maximum of 72% above control. It is concluded that during and after nitroprusside hypotension loss of cerebral autoregulation occurs which may result in a marked rise in intracranial pressure. Special vulnerability seems to exist shortly after termination of induced hypotension when arterial pressure begins to rise and brain perfusion follows a pressure-flow relationship.

Animals↗
PubMed1984

Effect of ganglionic blockade with trimethaphan on corticosteroid responses to metoclopramide in rhesus monkeys.

In order to investigate whether metoclopramide stimulates 18-hydroxycorticosterone and aldosterone production directly by way of the autonomic nervous system, we have examined the effects of ganglionic blockade with trimethaphan on the responses to metoclopramide (200 micrograms/kg) in rhesus monkeys. Trimethaphan, infused at a rate (200 micrograms/kg/min) which significantly decreased mean arterial pressure from 122 +/- 7 to 62 +/- 4 mmHg, did not alter the peak plasma 18-OHB and aldosterone responses to metoclopramide. These results suggest that 18-hydroxycorticosterone and aldosterone responses to metoclopramide occur independently of adrenergic neuronal input.

18-Hydroxycorticosterone↗
PubMed1985

Nitroprusside vs. a nitroprusside-trimethaphan mixture for induced hypotension: hemodynamic effects and cyanide release.

Changes in hemodynamic variables and whole blood cyanide and plasma thiocyanate concentrations associated with the infusion of sodium nitroprusside were compared with those during administration of a mixture of sodium nitroprusside (25 mg) and trimethaphan camsylate (250 mg) in a solution of 5% dextrose in water in twenty subjects who required deliberate hypotension for major orthopedic procedures. Subjects were randomly assigned to receive nitroprusside alone (group 1; n = 10) or the nitroprusside-trimethaphan mixture (group 2; n = 10). All subjects received a similar anesthetic technique, consisting of 5 mg/kg thiopental, 1 mg/kg succinylcholine, 1% halothane, 0.2 mg/kg metocurine, and 60% nitrous oxide in oxygen. Mean arterial pressure decreased and was maintained at 55 mm Hg for 258 +/- 4 and 266 +/- 8 minutes in groups 1 and 2. Arterial hypotension was associated with a rise in cardiac output and heart rate in group 1 but not in group 2. Subjects in group 2 required less nitroprusside than did those in group 1 (1.39 +/- 0.3 and 5.82 +/- 0.63 micrograms/kg/min) because of the synergistic or additive action of the combination. After 4 hours of hypotension, the whole blood cyanide level rose from 3.5 +/- 1.1 to 96.6 +/- 14.0 micrograms/dl (1.35 +/- 0.27 to 37.2 +/- 5.4 mumol/L) in group 1 and from 3.7 +/- 1.1 to 22.7 +/- 4.2 micrograms/dl (1.42 +/- 0.4 to 8.7 +/- 1.6 mumol/L) in group 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗