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The Journal of Clinical Endocrinology... Jul 2020Pretreatment with α-adrenergic receptor blockers is recommended to prevent hemodynamic instability during resection of a pheochromocytoma or sympathetic paraganglioma... (Randomized Controlled Trial)
Randomized Controlled Trial
CONTEXT
Pretreatment with α-adrenergic receptor blockers is recommended to prevent hemodynamic instability during resection of a pheochromocytoma or sympathetic paraganglioma (PPGL).
OBJECTIVE
To determine which type of α-adrenergic receptor blocker provides the best efficacy.
DESIGN
Randomized controlled open-label trial (PRESCRIPT; ClinicalTrials.gov NCT01379898).
SETTING
Multicenter study including 9 centers in The Netherlands.
PATIENTS
134 patients with nonmetastatic PPGL.
INTERVENTION
Phenoxybenzamine or doxazosin starting 2 to 3 weeks before surgery using a blood pressure targeted titration schedule. Intraoperative hemodynamic management was standardized.
MAIN OUTCOME MEASURES
Primary efficacy endpoint was the cumulative intraoperative time outside the blood pressure target range (ie, SBP >160 mmHg or MAP <60 mmHg) expressed as a percentage of total surgical procedure time. Secondary efficacy endpoint was the value on a hemodynamic instability score.
RESULTS
Median cumulative time outside blood pressure targets was 11.1% (interquartile range [IQR]: 4.3-20.6] in the phenoxybenzamine group compared to 12.2% (5.3-20.2)] in the doxazosin group (P = .75, r = 0.03). The hemodynamic instability score was 38.0 (28.8-58.0) and 50.0 (35.3-63.8) in the phenoxybenzamine and doxazosin group, respectively (P = .02, r = 0.20). The 30-day cardiovascular complication rate was 8.8% and 6.9% in the phenoxybenzamine and doxazosin group, respectively (P = .68). There was no mortality after 30 days.
CONCLUSIONS
The duration of blood pressure outside the target range during resection of a PPGL was not different after preoperative treatment with either phenoxybenzamine or doxazosin. Phenoxybenzamine was more effective in preventing intraoperative hemodynamic instability, but it could not be established whether this was associated with a better clinical outcome.
Topics: Adrenal Gland Neoplasms; Adrenergic alpha-Antagonists; Blood Pressure; Doxazosin; Female; Humans; Male; Middle Aged; Phenoxybenzamine; Pheochromocytoma; Treatment Outcome
PubMed: 31714582
DOI: 10.1210/clinem/dgz188 -
Frontiers in Endocrinology 2023Resection of pheochromocytoma and paraganglioma (PPGL) carries risks with perioperative hemodynamic instability. Phenoxybenzamine (PXB) is a commonly used α-blockade to...
Influence of duration of preoperative treatment with phenoxybenzamine and secretory phenotypes on perioperative hemodynamics and postoperative outcomes in pheochromocytoma and paraganglioma.
OBJECTIVES
Resection of pheochromocytoma and paraganglioma (PPGL) carries risks with perioperative hemodynamic instability. Phenoxybenzamine (PXB) is a commonly used α-blockade to prevent it. It is unclear whether lengthening the preoperative duration of PXB is better for hemodynamic stability and postoperative outcomes. Furthermore, different types of catecholamines have varying effects on perioperative hemodynamics. Thus, our study aimed to investigate the impact of the duration of preoperative preparation with PXB and secretory phenotypes of the patients on intraoperative hemodynamic stability and postoperative complications in PPGL.
METHODS
Between Dec 2014 and Jan 2022, 166 patients with PPGL were operated on by the same team at Sun Yat-sen Memorial Hospital. They were divided into group A(1-14d), Group B(15-21d), and Group C(>21d) based on the duration of management with PXB and into the adrenergic and the noradrenergic phenotype group based on secretory profiles. Data on intraoperative hemodynamics and postoperative outcomes were collected and compared among groups.
RESULTS
A total of 96 patients occurred intraoperative hemodynamic instability, and 24 patients had 29 postoperative complications related to the surgery. Among the 145 patients treated with PXB, no significant differences were found in the cumulative time outside the target blood pressure(6.67%[0-17.16%] 5.97%[0-23.08%] 1.22%[0-17.27%], =0.736) or in the median total HI-score(42.00[30.00-91.00] 89.00[30.00-113.00] 49.00[30.00-93.00], =0.150) among group A(n=45), B(n=51) and C(n=49). Multivariate analysis demonstrated that the level of plasma-free metanephrine(MN) was an independent risk factor for intraoperative hemodynamic instability. And the median cumulative time outside of the target blood pressure in the adrenergic phenotype group was significantly greater than that in the noradrenergic phenotype group(8.17%[0-26.22%] 1.86%[0-11.74%], =0.029). However, the median total HI-score(99.50[85.00-113.25] 90.00[78.00-105.00], =0.570) and postoperative outcomes showed no differences between the two groups.
CONCLUSIONS
A preoperative duration of nearly 14 days with PXB is sufficient for ensuring intraoperative hemodynamic stability in PPGL. And lengthening the preparation duration may not provide additional benefits in the era of widespread application and advanced techniques of laparoscopic surgery. Additionally, patients with the adrenergic phenotype are more prone to intraoperative hemodynamic instability than the noradrenergic phenotype. Thus, more attention should be given to the adrenergic phenotype during surgery.
Topics: Humans; Phenoxybenzamine; Pheochromocytoma; Paraganglioma; Hemodynamics; Metanephrine; Postoperative Complications; Norepinephrine; Adrenal Gland Neoplasms; Adrenergic Agents
PubMed: 37152936
DOI: 10.3389/fendo.2023.1139015 -
PloS One 2018The principal finding from this study was the recognition that the α-adrenergic antagonist, phenoxybenzamine, possesses histone deacetylase inhibitory activity....
The principal finding from this study was the recognition that the α-adrenergic antagonist, phenoxybenzamine, possesses histone deacetylase inhibitory activity. Phenoxybenzamine is approved by the United States Food and Drug Administration for the treatment of hypertensive crises associated with tumors of the adrenal medulla, pheochromocytomas. It has several "off label" indications relative to its capacity to relax vascular smooth muscle and smooth muscle of the urogenital tract. The drug also has a long history of apparent efficacy in ameliorating, and perhaps reversing, the severe symptoms of neuropathic pain syndromes. Our interest in this feature of the drug relates to the fact that certain types of neuropathic pain, in particular complex regional pain syndrome, demonstrate a proliferative nature, with the capacity to spread from an injured limb, for example, to a non-injured limb and perhaps to essentially the entire body. Sensory neuronal sprouting in the spinal cord has been observed under conditions where there is a high sensory input from painful stimuli. Searches of gene expression signatures in the BroadBuild02 Molecular Signature Database using their connectivity map software suggested that phenoxybenzamine may have histone deacetylase inhibitory activity. Studies by others have reported inhibitory effects of phenoxybenzamine on growth, invasion and migration of human tumor cell cultures and, in one study, inhibition of tumor expansion in animal experiments. Inhibitory effects on human tumor cell cultures are also reported in the present study. Phenoxybenzamine was also found to have histone deacetylase inhibitory activity; histone deacetylase isoforms 5, 6, and 9 were the most sensitive to inhibition by phenoxybenzamine. The importance of elevated levels of these isoforms as biomarkers of poor prognosis in human malignant disease, and the recognized suppression of tumor growth that may accrue from their inhibition, opens consideration of possible translation of phenoxybenzamine to new clinical applications. This might be facilitated by the fact that phenoxybenzamine is already an approved drug entity. There appears to be no previous report of the activity of phenoxybenzamine as a histone deacetylase inhibitor.
Topics: Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Databases, Factual; Histone Deacetylases; Humans; Inhibitory Concentration 50; Isoenzymes; Neoplasms; Phenoxybenzamine
PubMed: 29897996
DOI: 10.1371/journal.pone.0198514 -
The Netherlands Journal of Medicine May 2014During surgical treatment of pheochromocytoma,`haemodynamic instability may occur. To prevent this, patients receive preoperative treatment with an alpha-blocker.... (Review)
Review
BACKGROUND
During surgical treatment of pheochromocytoma,`haemodynamic instability may occur. To prevent this, patients receive preoperative treatment with an alpha-blocker. Nowadays, some centres use phenoxybenzamine, while others use doxazosin. The purpose of this review is to analyse the current evidence of the benefits and risks of phenoxybenzamine and doxazosin in the preoperative treatment of pheochromocytoma.
METHODS
The literature was reviewed by searching PubMed using the following search terms: pheochromocytoma, phenoxybenzamine, doxazosin and alpha-blockade. The filter was set on English language.
RESULTS
No randomised controlled trials were found. Five follow-up studies comparing phenoxybenzamine and doxazosin in the treatment of pheochromocytoma were retrieved and analysed. There was a trend that systolic arterial pressure is slightly better controlled by phenoxybenzamine. However, this resulted in more pronounced postoperative hypotension as well. The use of an alpha-blocker was often accompanied by other vasoactive agents. phenoxybenzamine was often accompanied by a beta-blocker to control reflex tachycardia, while patients on doxazosin received significantly more additional antihypertensive medicines. Most of the studies showed that the use of vasoactive drugs and fluid infusion does not differ significantly between the two drugs. Phenoxybenzamine caused significantly more orthostatic hypotension, oedema and complaints of a stuffy nose.
CONCLUSION
On the basis of the current evidence, there is no evidently superior alpha-blocker for the pretreatment of patients with pheochromocytoma. Perioperative haemodynamics seem to be slightly better controlled with phenoxybenzamine, at the cost of more pronounced postoperative hypotension. Side effects occurred less often in the doxazosin group.
Topics: Adrenal Gland Neoplasms; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Blood Pressure; Doxazosin; Humans; Phenoxybenzamine; Pheochromocytoma; Preoperative Care
PubMed: 24829175
DOI: No ID Found -
Endocrine Practice : Official Journal... Sep 2022Phenoxybenzamine (nonselective, noncompetitive alpha-blocker) is the preferred drug for preoperative treatment of pheochromocytoma, but doxazosin (selective, competitive...
OBJECTIVE
Phenoxybenzamine (nonselective, noncompetitive alpha-blocker) is the preferred drug for preoperative treatment of pheochromocytoma, but doxazosin (selective, competitive alpha-blocker) may be equally effective. We compared the efficacy of doxazosin vs phenoxybenzamine.
METHODS
We conducted a prospective study of patients undergoing pheochromocytoma or paraganglioma resection by randomizing pretreatment with phenoxybenzamine or doxazosin at a single tertiary referral center. The high cost of phenoxybenzamine led to high crossover to doxazosin. Randomization was halted, and a consecutive historical cohort of phenoxybenzamine patients was included for a case-control study design. The efficacy of alpha-blockade was assessed with preinduction infusion of incremental doses of phenylephrine. The primary outcomes were mortality, cardiovascular complications, and intensive care unit admission. The secondary outcomes were hemodynamic instability index (proportion of operation outside of hemodynamic goals), adequacy of blockade by the phenylephrine titration test, and drug costs.
RESULTS
Twenty-four patients were prospectively enrolled (doxazosin, n = 20; phenoxybenzamine, n = 4), and 15 historical patients treated with phenoxybenzamine were added (total phenoxybenzamine, n = 19). No major cardiovascular complications occurred in either group. The phenylephrine dose-response curves showed less blood pressure rise in the phenoxybenzamine than in the doxazosin group (linear regression coefficient = 0.008 vs 0.018, P = .01), suggesting better alpha-blockade in the phenoxybenzamine group. The median hemodynamic instability index was 14% vs 13% in the phenoxybenzamine and doxazosin groups, respectively (P = .56). The median highest daily cost of phenoxybenzamine was $442.20 compared to $5.06 for doxazosin.
CONCLUSION
Phenoxybenzamine may blunt intraoperative hypertension better than doxazosin, but this difference did not translate to fewer cardiovascular complications and is offset by a considerably increased cost.
Topics: Adrenal Gland Neoplasms; Adrenergic alpha-Antagonists; Case-Control Studies; Doxazosin; Humans; Phenoxybenzamine; Phenylephrine; Pheochromocytoma; Prospective Studies
PubMed: 35809774
DOI: 10.1016/j.eprac.2022.06.013 -
Endocrine Dec 2021To identify presurgical and surgical risk factors for postsurgical complications in the pheochromocytoma surgery.
PURPOSE
To identify presurgical and surgical risk factors for postsurgical complications in the pheochromocytoma surgery.
METHODS
A retrospective study of pheochromocytomas submitted to surgery in ten Spanish hospitals between 2011 and 2021. Postoperative complications were classified according to Clavien-Dindo scale.
RESULTS
One hundred and sixty-two surgeries (159 patients) were included. Preoperative antihypertensive blockade was performed in 95.1% of the patients, being doxazosin in monotherapy (43.8%) the most frequent regimen. Patients pre-treated with doxazosin required intraoperative hypotensive treatment more frequently (49.4% vs 25.0%, P = 0.003) than patients treated with phenoxybenzamine, but no differences in the rate of intraoperative and postsurgical complications were observed. However, patients treated with phenoxybenzamine had a longer hospital stay (12.2 ± 11.16 vs 6.2 ± 6.82, P < 0.001) than those treated with doxazosin. Hypertension resolution was observed in 78.7% and biochemical cure in 96.6% of the patients. Thirty-one patients (19.1%) had postsurgical complications. Prolonged hypotension was the most common, in 9.9% (n = 16), followed by hypoglycaemia in six patients and acute renal failure in four patients. 13.0% of complications had a score ≥3 in the Clavien-Dindo scale. Postsurgical complications were more common in patients with diabetes, cerebrovascular disease, higher plasma glucose levels, higher urinary free metanephrine and norepinephrine, and with pheochromocytomas larger than 5 cm.
CONCLUSION
Preoperative medical treatment and postsurgical monitoring of pheochromocytoma should be especially careful in patients with diabetes, cerebrovascular disease, higher levels of plasma glucose and urine free metanephrine and norepinephrine, and with pheochromocytomas >5 cm, due to the higher risk of postsurgical complications.
Topics: Adrenal Gland Neoplasms; Humans; Phenoxybenzamine; Pheochromocytoma; Retrospective Studies; Treatment Outcome
PubMed: 34373995
DOI: 10.1007/s12020-021-02843-6 -
Report on Carcinogens : Carcinogen... 2011
Topics: Animals; Antihypertensive Agents; Carcinogens; Humans; Neoplasms; Phenoxybenzamine; Vasodilator Agents
PubMed: 21863081
DOI: No ID Found -
Kardiologia Polska 2017Adrenalectomy with preoperative pharmacological preparation is strongly recommended in patients diagnosed with pheochromocytoma, in order to prevent perioperative... (Comparative Study)
Comparative Study
BACKGROUND
Adrenalectomy with preoperative pharmacological preparation is strongly recommended in patients diagnosed with pheochromocytoma, in order to prevent perioperative complications.
AIM
To compare phenoxybenzamine (PhB) and doxazosin (DOX) in terms of perioperative haemodynamic status in patients with pheochromocytoma, who have been prepared for adrenalectomy.
METHODS
Retrospective analysis of 44 patients with pheochromocytoma (aged 16-80 years, 29 females) who underwent adrenalectomy. Patients were divided into two groups: 35 patients on DOX and nine patients on PhB.
RESULTS
Mean time of preparation for surgery was 38.8 days in the DOX group and 18.3 days in the PhB group (p = 0.04). No statistically significant differences between the DOX and PhB groups in intraoperative blood pressure (BP) fluctuations were found: < 170/100 mm Hg (34% vs. 44%, respectively, p = 0.42), ≥ 200/110 mm Hg (40% vs. 22%, respectively, p = 0.28). Mean greatest intraoperative systolic BP (195 ± 53 vs. 166 ± 42 mm Hg, p = 0.21) and diastolic BP (98 ± 20 vs. 89 ± 46 mm Hg, p = 0.21), and mean lowest intraoperative systolic BP (87 ± 13 vs. 79 ± 17 mm Hg, p = 0.25) and diastolic BP (49 ± 8 vs. 46 ± 12 mm Hg, p = 0.60) were not different between the DOX and PhB groups, respectively. Sodium nitroprusside was administrated in 30% DOX vs. 11% PhB patients (p = 0.25). Laparoscopic surgery was conducted in 97% DOX vs. 89% PhB patients (p = 0.64). Postoperative BP drop below 90/60 mm Hg was noted in 48% of the DOX vs. 43% of the PhB group (p = 0.56). Negative correlation was found between the length of DOX administration with maximal intraoperative systolic BP (r = -0.45, p = 0.006) and diastolic BP (r = -0.39, p = 0.019).
CONCLUSIONS
There are no clinically relevant differences between patients with pheochromocytoma, who have been prepared for adrenalectomy with DOX or PhB.
Topics: Adrenalectomy; Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Blood Pressure; Disease Management; Doxazosin; Female; Humans; Male; Middle Aged; Phenoxybenzamine; Pheochromocytoma; Postoperative Complications; Prohibitins; Retrospective Studies; Young Adult
PubMed: 28715066
DOI: 10.5603/KP.a2017.0147 -
The Annals of Thoracic Surgery Feb 2007
Topics: Coronary Artery Bypass; Humans; Intraoperative Complications; Myocardial Infarction; Phenoxybenzamine; Postoperative Complications; Preoperative Care; Radial Artery; Vasodilator Agents
PubMed: 17257978
DOI: 10.1016/j.athoracsur.2006.10.043 -
Canadian Medical Association Journal Nov 1963Bacteremic shock is second in frequency only to myocardial infarction as a cause of hypotension and death in hospitalized medical patients. The clinical course is marked...
Bacteremic shock is second in frequency only to myocardial infarction as a cause of hypotension and death in hospitalized medical patients. The clinical course is marked by fever, usually with chills, and hypotension with a full pulse and warm extremities, followed by shock, often resistant to treatment. Anticipation of this complication in patients with certain predisposing diseases or factors facilitates early recognition of the symptoms and signs of bacteremic shock and prompt treatment. Early and effective treatment of the offending infection often prevents progression of hypotension to the stage of frank vascular collapse.
Topics: Anti-Bacterial Agents; Antibiotics, Antitubercular; Emergencies; Humans; Hypotension; Metaraminol; Methicillin; Myocardial Infarction; Norepinephrine; Phenoxybenzamine; Sepsis; Shock; Shock, Septic; Streptomycin; Tetracycline
PubMed: 14079124
DOI: No ID Found