Perioperative hemodynamic instability in pheochromocytoma and sympathetic paraganglioma patients

For pheochromocytoma and sympathetic paraganglioma (PPGL), surgery can be used as a curative treatment; however, the life-threatening risk of perioperative hemodynamic instability (HI) presents challenges. This study aimed to analyze the incidence and predictive factors of perioperative HI. The electronic medical records of 114 consecutive patients who underwent surgery for PPGLs at our institution were retrospectively reviewed. HI was defined as one or more episodes of systolic blood pressure > 200 mmHg or mean blood pressure < 60 mmHg during surgery. The factors predictive of perioperative HI were determined using both univariate and multivariate analyses. Intraoperative HI occurred in 79 (69.3%) patients. In multivariate analysis, α-adrenergic receptor blocker duration (days) (odds ratio, 1.015; 95% confidence interval, 1.001–1.029) was a predictor for intraoperative HI. Postoperative hypotension occurred in 36 (31.6%) patients. Higher urine epinephrine levels, and greater preoperative highest heart rate (HR) were predictive factors for postoperative hypotension in PPGL patients. Caution should be taken in perioperative management for PPGL, especially with long duration of α-adrenergic receptor blocker use, higher urine epinephrine levels, and greater preoperative highest HR.

Selective versus non-selective alpha-blockade prior to adrenalectomy for pheochromocytoma – systematic review and meta-analysis

Objective: Alpha-adrenergic blockade is currently the first choice of preoperative treatment in patients with functional pheochromocytoma and sympathetic paraganglioma. Nevertheless, there is no consensus whether selective or non-selective alpha-blockade is superior for preventing both perioperative hemodynamic instability and complications. Design: Our study aimed to compare selective and non-selective alpha-blockade through a systematic review with meta-analysis. Methods: MEDLINE, Embase, Web of Science and Cochrane Library were searched for eligible studies. Randomized and observational studies comparing selective and non-selective alpha-blockade in pheochromocytoma and sympathetic paraganglioma surgery in adults were included. Data on perioperative hemodynamic parameters and postoperative outcomes were extracted. Results: Eleven studies with 1,344 patients were enrolled. Patients receiving selective alpha-blockade had higher maximum intraoperative systolic blood pressure (WMD 12.14 mm Hg, 95% CI 6.06-18.21, p<0.0001) compared to those treated with non-selective alpha-blockade. Additionally, in the group pretreated with selective alpha-blockers, intraoperative vasodilators were used more frequently (OR 2.46, 95% CI 1.44-4.20, p=0.001). Patients treated with selective alpha-blockers had lower minimum intraoperative systolic blood pressure (WMD -2.03 mmHg, 95% CI -4.06 to -0.01, p=0.05) and shorter length of hospital stay (WMD -0.58 days, 95% CI -1.12 to -0.04, p=0.04). Operative time, overall morbidity and mortality did not differ between the groups. Conclusions: This meta-analysis shows non-selective alpha-blockade was more effective in preventing intraoperative blood pressure fluctuations while maintaining comparable risk of both intraoperative and postoperative hypotension and overall morbidity.

Incidence and Clinical Presentation of Pheochromocytoma and Sympathetic Paraganglioma: A Population-based Study

Context Pheochromocytoma and sympathetic paraganglioma (PPGL) are rare catecholamine-secreting tumors but recent studies suggest increasing incidence. Traditionally, PPGL are described to present with paroxysmal symptoms and hypertension, but existing data on clinical presentation of PPGL come from referral centers. Objective We aimed to describe time trends in clinical presentation and incidence of PPGL in a population-based study. Methods We conducted a nationwide retrospective cohort study of a previously validated cohort of 567 patients diagnosed with PPGL in Denmark 1977-2015. We collected clinical data from medical records of a geographic subcohort of 192 patients. We calculated age-standardized incidence rates (SIRs) and prevalence for the nationwide cohort and descriptive statistics on presentation for the subset with clinical data. Results SIRs increased from 1.4 (95% CI 0.2-2.5) per million person-years in 1977 to 6.6 (95% CI 4.4-8.7) per million person-years in 2015, corresponding to a 4.8-fold increase. The increase was mainly due to incidentally found tumors that were less than 4 cm and diagnosed in patients older than 50 years with no or limited paroxysmal symptoms of catecholamine excess. On December 31, 2015, prevalence of PPGL was 64.4 (CI 95% 57.7-71.2) per million inhabitants. Of 192 patients with clinical data, 171 (89.1%) had unilateral pheochromocytoma, while unilateral paraganglioma (n = 13, 6.8%) and multifocal PPGL (n = 8, 4.2%) were rare. Conclusion Incidence of PPGL has increased 4.8-fold from 1977 to 2015 due to a “new” group of older patients presenting with smaller incidentally found PPGL tumors and few or no paroxysmal symptoms.

Blood sampling for metanephrines comparing venipuncture vs. indwelling intravenous cannula in healthy subjects

BackgroundTo diagnose pheochromocytoma or sympathetic paraganglioma, guidelines recommend blood sampling after at least 30 min of supine rest and using an indwelling intravenous cannula is preferred. Although blood sampling by venipuncture is more convenient and cost-effective, it is unknown whether venipuncture affects plasma concentrations of free metanephrines (MNs). We therefore investigated whether there is a difference in plasma concentrations of free MNs collected by venipuncture or by an intravenous cannula.MethodsWe included 22 healthy participants (12 men and 10 women, median age 26 years). We collected blood using an indwelling cannula and venipuncture to determine plasma concentrations of free MNs and catecholamines, and calculated the median of the individually calculated absolute and relative differences.ResultsPlasma concentrations of free MN, normetanephrine (NMN) and epinephrine were higher with blood sampling using venipuncture compared to that when using an indwelling cannula. The median (interquartile range [IQR]) difference was MN 0.020 (−0.004 to 0.040) nmol/L, median percentage difference 20.5% (−2.4 to 35.2%), NMN 0.019 (−0.004 to 0.077) nmol/L, median percentage difference 4.6% (−1.1 to 25.4%) and epinephrine 0.022 (0.007–0.079) nmol/L, median percentage difference 24.9% (7.8–83.3%). When the two sampling conditions were compared, plasma-free 3-methoxytyramine (3-MT), norepinephrine and dopamine concentrations did not differ.ConclusionsBlood sampling by venipuncture resulted in statistically significant higher concentrations of MN, NMN and epinephrine compared to sampling by means of an indwelling cannula. However, differences were small. For most patients it seems justifiable to collect blood via venipuncture.

Approach to the Patient: Perioperative Management of the Patient with Pheochromocytoma or Sympathetic Paraganglioma

Pheochromocytomas and sympathetic paraganglioma (PPGL) are rare chromaffin cell tumors originating in the adrenal medulla and sympathetic paraganglia, respectively, which share the capacity to synthesize and release catecholamines. The incidence of PPGL has increased in recent years. Surgical resection is the only curative treatment for PPGL. Management of patients with PPGL is complex and should be done by a specialized multidisciplinary team in centers with broad expertise. Surgical resection of a PPGL is a high-risk procedure for which optimal pretreatment with antihypertensive drugs is required in combination with state-of-the-art surgical procedures and anesthesiological techniques. In this article we discuss the underlying evidence and the pros and cons of presurgical medical preparation. Finally, the areas of uncertainty and controversies in this field are addressed.