Preoperative α-blockade versus no blockade for pheochromocytoma–paraganglioma patients undergoing surgery: a systematic review and updated meta-analysis

Background:

Surgical resection of pheochromocytomas and paragangliomas (PPGLs) is associated with a significant risk of intraoperative hemodynamic instability and cardiovascular complications. α-blockade remains the routine preoperative medical preparation despite controversies over the lack of evidence. We presented an updated meta-analysis to ulteriorly evaluate the potential efficacy of preoperative α-blockade versus no blockade for PPGL patients undergoing surgery.

Materials and methods:

Randomized and nonrandomized comparative studies assessing preoperative α-blockade for PPGL surgery in adults were identified through a systematic literature search via MEDLINE, Embase, Web of Science, and CENTRAL up to November 2022. Outcome data of intraoperative hemodynamic parameters and major postoperative events were extracted. Mean difference and risk ratio were synthesized as appropriate for each outcome to determine the cumulative effect size.

Results:

Fifteen nonrandomized studies involving 3542 patients were finally eligible. Intraoperatively, none of the analyzed hemodynamic parameters differed between patients with or without α-blockade: maximum and minimum systolic blood pressure, hypertensive and hypotensive hemodynamic instability episodes, and peak heart rate, subgroup analysis of normotensive PPGL patients yielded similar results with the overall effects. Postoperatively, α-blockade was associated with prolonged hypotension and vasopressor usage (risk ratio: 4.21, 95% CI: 1.17–15.18, P=0.03). ICU admission, length of stay, overall cardiovascular morbidity, and mortality were similar between the two groups.

Conclusions:

Preoperative α-blockade ensured neither more stable intraoperative hemodynamics nor better perioperative outcome over no blockade for PPGL surgery. However, large-volume randomized controlled trials are still warranted to ascertain these findings.

Introduction

Highlights

• Eleven new studies were eligible for this updated meta-analysis.

• Preoperative α-blockade demonstrated no beneficial efficacy over no blockade.

• These findings were consistent in both normotensive and hypertensive patients.

Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors deriving from chromaffin cells of the adrenal medulla and extra-adrenal ganglia, characterized by the episodic release of catecholamines that may arouse drastic blood pressure fluctuation and even life-threatening multiorgan dysfunction. Surgical removal remains the only curative option for localized PPGL. The procedure involves a significant risk of intraoperative hemodynamic instability (HDI) and cardiovascular complications like stroke, left ventricular failure, and myocardial infarction1,2. Historically, perioperative mortality reached as high as 20–45% in functional PPGL patients3,4.

According to relevant guidelines, systemic α-blockade with selective or nonselective blockers should be accomplished routinely before PPGL resections, even with biochemically silent and normotensive patients5–8. It was advocated to correct catecholamine-related vasoconstriction and hypovolemia by blocking α1-adrenoceptor. However, these recommendations were almost entirely based on observational findings and expert consensus rather than convincing evidence, with the absence of randomized controlled studies5,9.

Overall perioperative major morbidity and mortality of PPGL surgeries has fallen steadily to less than 1–3% contemporarily since the introduction of α-blockade pretreatment7,10,11. However, the extent of their correlations remains doubtful, considering the profound evolvement of diagnostic modalities, anesthetic monitoring, as well as surgical approaches. Recent studies indicated that despite optimal α-blockade, intraoperative hemodynamic fluctuations were still common but rarely associated with major cardiovascular events12,13. Prolonged α-blockade predicted more perioperative hypotension episodes14. Consequently, pheochromocytoma surgery omitting preoperative α-blockade and even hypotensors is safe and feasible for selected patients15,16. Hence the dogmatic α-blockade modality before PPGL surgery necessitates a comprehensive appraisal.

Herein, we conducted a systematic review and updated meta-analysis of the current literature to evaluate the efficacy of α-blockade pretreatment for PPGL patients undergoing surgical resections regarding intraoperative hemodynamics and postoperative events.

Materials and methods

The protocol was formulated a priori and registered in the International Prospective Register of Systematic Reviews (PROSPERO) (ID: CRD42022370263). This meta-analysis has been formulated following PRISMA standards and complies with the PRISMA 2020 statement17.

Search strategy

A comprehensive literature search of the electronic databases MEDLINE (via PubMed), Embase, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL) was performed by two independent reviews up to 6 November 2022. The search strategy for MEDLINE consisted of the key search terms ‘pheochromocytoma,’ ‘paraganglioma,’ ‘surgery,’ ‘adrenalectomy,’ and their synonyms, as well as related Medical Subject Headings (MeSH) terms combined with ‘alpha-blockade’ and the associated medications (‘phenoxybenzamine,’ ‘doxazosin,’ ‘prazosin,’ ‘terazosin,’ et al.). No restriction on language and the publication date was predefined. The reference lists of relevant studies were manually screened to reduce omission.

Study eligibility

Inclusion: Randomized controlled trials (RCTs), nonrandomized prospective and retrospective studies comparing preoperative α-blockade with no blockade in histologically confirmed PPGL patients undergoing surgery concerning intraoperative hemodynamics and/or perioperative morbidity and mortality.

Exclusion: All other designs like reviews, meeting abstracts, comments, and editorials; Studies involving animals, pediatric participants, or surgeries other than PPGL resections; irrelevant outcomes or sufficient outcome data not retrievable.

The study screening and inclusion process was carried out by two reviewers independently. Any disagreement was resolved by consultation with a third reviewer.

Data extraction

A standardized form was formulated for data extraction. The following items of demographic and clinical details were recorded: country(s), center(s), study design, study period, number of participants, α-blockade regimen, sex ratio, approach, and site of surgery. The outcome measurements described below were extracted synchronously. If multiple comparisons of nonselective phenoxybenzamine and selective α-blockers were presented in a single study, combined patient data of all α-blocked procedures were calculated for analysis. Data extraction was conducted by two reviewers independently. Any discrepancy was resolved by consensus or consulting a third author. The valid data was recorded in an excel spreadsheet for analysis.

Outcome measures

The intraoperative outcome measures were intraoperative hypertensive HDI episode (defined as maximum systolic blood pressure>200 mmHg), hypotensive HDI episode (defined as minimum systolic blood pressure<80 mmHg or mean arterial pressure<60 mmHg), mean maximum systolic blood pressure, mean minimum systolic blood pressure, and mean highest heart rate. The postoperative outcome measures were postoperative vasopressor usage, cardiovascular complications, ICU admission, length of stay, and mortality.

Quality assessment

The Cochrane Collaboration tool was utilized for quality assessment of RCTs, including indexes of randomization sequencing, allocation concealment, blinding to personnel and participants, blinding of outcome assessment, incomplete outcome data, selective report of results, and other bias18. The Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool was employed to assess the quality of included nonobservational studies, involving bias associated with confounding, selection of participants into the study, classification of intervention, deviations from intended interventions, missing data, outcome measurement, and selection of the reported result19. Two independent reviewers assessed the quality of each study. In case of discrepancy, a third reviewer was consulted until consistency was achieved.

Statistical analysis

Meta-analyses were performed using the Review Manager version 5.3 (The Cochrane Collaboration) and Stata SE 15.1 (StataCorp LLC) software package. Risk ratio (RR) and 95% CI was pooled for dichotomous outcomes using the Mantel–Haenszel method. Continuous outcomes were pooled as mean difference (MD) with 95% CI with the inverse variance method. In studies where outcomes were reported as medians and quartiles, means and SDs were calculated using methods proposed by Luo et al.20 and Wan et al 21. The I ² test was utilized to quantify the effects of heterogeneity among the studies (I ²<25% and >75% values correspond to low and high statistical heterogeneity, respectively). Subgroup analyses and sensitivity analyses were performed as appropriate to explore possible causes of heterogeneity among study results.

Result

The literature search and eligibility

The initial literature search yielded 1871 records. After duplicate removal, titles and abstracts screening was conducted for 545 articles, of which 26 relevant studies were retrieved for full-text analysis. Finally, four studies from the previous review and 11 new studies were eligible for the qualitative and quantitative analysis, involving 3824 procedures performed in 3542 participants (282 patients had multiple resections due to bilateral, multifocal, or relapsed tumors) from 12 countries22–36, of which 2636 received preoperative α-blockade and 906 without α-blockade. All studies were nonrandomized, comprising three prospective cohort studies26,28,29 and 12 retrospective studies22–25,27,30–36.

There were studies concerning the same author28,31 or the same affiliation22,24, which resulted in a possible overlap of total participants. However, they were not excluded from the quantitative analysis because different outcomes of interest were involved. Figure 1 shows the flow diagram of the literature search and inclusion process arranged according to the PRISMA 2020 statement.

Figure 1.

PRISMA flow diagram.

Description of studies

The main characteristics of eligible studies are presented in Table 1. There were four multi-institutional studies27,31,32,34 and one based on statistics retrieved from a national database36. The sex ratio is similar between groups. Nonselective phenoxybenzamine was used in the majority, followed by selective α-blockers of doxazosin, terazosin, and prazosin. The course of preoperative α-blockade was deemed adequate between 7 days to more than 3 weeks in most studies. Monotherapy or combinations with other hypotensive drugs were noticed in both groups of α-blockade and no blockade, as per targets of adequate preoperative medication management for the individuals, of which β-blockers and calcium channel blockers were mostly used. Three studies25,26,30 and one34 only recruited normotensive and biochemically silent PPGL patients, respectively.

Table 1.

Main characteristics of eligible studies

					Surgical procedures		α-blockade regimen
References	Country(s)	Center(s)	Design	Study period	α-blockade	No blockade	Drug(s)	Course	Sex (male:female)	Open/laparoscopic	Adrenal/extra-adrenal
Boutros et al. 22	USA	1	Retrospective	1978–1988	34	29	PBZ or PRA	7 days	NA	Yes/no	Yes/yes
Steinsapir et al. 23	USA	1	Retrospective	1959–1996	6	7	PBZ	≥3 weeks	6:7	Yes/no	Yes/yes
Ulchaker et al. 24	USA	1	Retrospective	1977–1994	79	34	PBZ or SAB	NA	53:60	Yes/no	Yes/yes
Agarwal et al. 25	India	1	Retrospective	1990–2003	7	2	PRA	Mean: 9.5 days (9–15 days)	1:8	Yes/no	Yes/yes
Shao et al. 26	China	1	Prospective	2003–2011	38	21	DOX	14 days	26:33	Yes/yes	Yes/no
Brunaud et al. 27	France	3	Retrospective	2002–2012	41	4	PBZ	≥10 days	16:29	No/yes	Yes/no
Groeben et al. 28	Germany	1	Retrospective	2008–2016	110	166	PBZ or DOX	NA	153:150	Yes/yes	Yes/yes
Liu et al. 29	China	1	Prospective	2007–2016	492	23	PBZ or SAB	Mean: 13.5 days	166:200	Yes/no	Yes/no
Kong et al. 30	China	1		2008–2017	45	25	PBZ or DOX	≥7 days	NA	Yes/yes	Yes/yes
Groeben et al. 31	Australia, Germany, Ireland, Japan, The Netherlands, and USA	21	Prospective	2000–2017	1517	343	PBZ or SAB	NA	NA	Yes/yes	Yes/yes
Buscemi et al. 32	Italy	2	Retrospective	2000–2017	49	14	PBZ or DOX	2–7d before admission; 5–10 days after admission	27:36	No/yes	Yes/no
Furnica et al. 33	Belgium	1	Retrospective	1988–2018	29	51	PRA	≥14 days Median: 30 days	39:41	Yes/yes	Yes/no
Fountas et al. 34	Greece	2	Retrospective	2014–2021	5	5	PBZ	Mean: 14 days	5:5	Yes/yes	Yes/no
Liu et al. 35	China	1	Retrospective	2000–2017	61	106	PBZ or TER	≥14 days	79:88	Yes/yes	No/yes
Kuo et al. 36	USA	Nationwide database	Retrospective	2008–2019	405	76	PBZ or SAB	NA	148:219	Yes/yes	Yes/no

DOX, doxazosin; NA, data not available; PBZ, phenoxybenzamine; PRA, prazosin; SAB, selective α-blockers; TER, terazosin.

Quality assessment

Quality assessment with the ROBINS-I tool was presented in Table 2. Only one study was deemed a low overall risk of bias, in which confounders like age, duration of surgery, tumor size, tumor etiology, and catecholamine production were adjusted by propensity score matching28. All the observational studies were judged to have a moderate to serious risk of bias for their intrinsic confounders associated with patient selection, intervention allocation, or insufficient information. Data integrity, outcome measurement, and selection of reported results were deemed adequate in most studies.

Table 2.

Risk of bias assessment with the ROBINS-I tool

References	Bias due to confounding	Bias in selection of participants into the stud y	Bias in classification of intervention	Bias due to deviations from intended interventions	Bias due to missing data	Bias in measurement of outcomes	Bias in selection of the reported result	Overall risk of bias
Boutros et al. 22	2	2	1	2	1	1	1	Moderate risk of bias
Steinsapir et al. 23	3	3	1	1	1	1	1	Serious risk of bias
Ulchaker et al. 24	3	3	1	1	1	1	1	Serious risk of bias
Agarwal et al. 25	2	2	1	1	1	1	1	Serious risk of bias
Shao et al. 26	2	2	1	1	1	1	1	Moderate Risk of bias
Brunaud et al. 27	2	3	1	1	1	1	1	Serious risk of bias
Groeben et al. 28	1	1	1	1	1	1	1	Low risk of bias
Liu et al. 29	2	1	1	1	1	1	1	Moderate risk of bias
Kong et al. 30	2	2	1	1	2	1	1	Moderate risk of bias
Groeben et al. 31	2	2	2	1	1	1	1	Moderate risk of bias
Buscemi et al. 32	2	1	1	1	1	1	1	Moderate risk of bias
Furnica et al. 33	2	2	1	2	1	1	1	Moderate risk of bias
Liu et al. 35	3	3	1	1	1	1	1	Serious risk of bias
Fountas et al. 34	2	2	1	1	1	1	1	Moderate risk of bias
Kuo et al. 36	3	2	3	3	3	1	2	Serious risk of bias

0=no information/unclear, 1=low risk, 2=moderate risk, 3=serious risk, 4=critical risk of bias.

ROBINS-I, Risk Of Bias In Non-randomized Studies of Interventions.

Intraoperative hemodynamic outcomes

Maximum systolic blood pressure

Nine studies reported the maximum intraoperative systolic blood pressure, involving 879 procedures with preoperative α-blockade and 388 without23–30,35. No difference was shown in the pooled result between groups: MD=0.98 (−5.06, 7.02) mmHg (P=0.75, I ²=40%). Subgroup analysis of three studies25,26,30 comprising only normotensive PPGL patients showed a similar result: MD=−2.84 (−13.95, 8.27) mmHg (P=0.54, I ²=0%) (Fig. 2).

Figure 2.

Forest plot of intraoperative maximum systolic blood pressure comparing α-blockade with no blockade. PPGL, pheochromocytoma and paraganglioma.

Minimum systolic blood pressure

Seven studies reported the minimum intraoperative systolic blood pressure, involving 763 procedures with preoperative α-blockade and 215 without24–27,29,30,35. The pooled result showed a lower value associated with α-blockade, but the difference was not statistically significant: MD=−4.53 (−11.86, 2.79) mmHg (P=0.23, I ²=85%). Subgroup analysis of two studies with normotensive PPGL patients26,30 showed a minimal difference: MD=−0.88 (−5.84, 4.07) mmHg (P=0.62, I ²=0%) (Fig. 3).

Figure 3.

Forest plot of intraoperative minimum systolic blood pressure comparing α-blockade with no blockade. PPGL, pheochromocytoma and paraganglioma.

Hypertensive hemodynamic instability episode

Intraoperative hypertensive HDI, defined as at least one episode of systolic blood pressure above 200 mmHg, was reported in three studies of 356 procedures28,30,34. The pooled result showed no difference in hypertensive HDI incidence: RR=0.82 (0.50, 1.35) (P=0.44, I ²=0%) (Fig. 4).

Figure 4.

Forest plot of intraoperative hypertensive hemodynamic instability episode comparing α-blockade with no blockade.

Hypotensive hemodynamic instability episode

Intraoperative hypotensive HDI, defined as at least one episode of systolic blood pressure below 80 mmHg or mean arterial pressure below 60 mmHg, was reported in four studies of 523 procedures28,30,34,35. There was also no significant difference between groups: RR=1.07 (0.81, 1.41) (P=0.65, I ²=34%) (Fig. 5).

Figure 5.

Forest plot of intraoperative hypotensive hemodynamic instability episode comparing α-blockade with no blockade.

Highest heart rate

Peak heart rate was reported in six studies involving 417 procedures22,23,26,27,30,35. Synthesized results showed no significant variation in overall effect: MD=3.58 (−1.42, 8.57) (P=0.16, I ²=27%), as well as in subgroup analysis of two studies focusing on normotensive patients26,30: MD=−0.74 (−7.20, 5.73) (P=0.82, I ²=0%) (Fig. 6).

Figure 6.

Forest plot of intraoperative highest heart rate comparing α-blockade with no blockade. PPGL, pheochromocytoma and paraganglioma.

Postoperative outcomes

ICU admission

Five studies investigated postoperative ICU admission, involving 854 procedures22,32,33,35,36. The meta-analytic result showed a similar admission rate between groups: RR=1.29 (0.54, 3.09) (P=0.56, I ²=66%) (Fig. 7A).

Figure 7.

Forest plot of major postoperative events comparing α-blockade with no blockade. ICU admission (A), vasopressor usage (B), length of stay (C), and overall cardiovascular morbidity (D).

Vasopressor usage

Prolonged postoperative hypotension that necessitated vasopressor usage was noted in three studies with 243 procedures22,23,35. Patients with α-blockade pretreatment had a significantly higher risk of postoperative hypertension than those without: RR=4.21 (1.17, 15.18) (P=0.03, I ²=0%) (Fig. 7B).

Length of stay

The pooled result of four studies29,32,35,36 demonstrated a similar postoperative length of stay between groups: MD=0.58 (−1.02, 2.18) days (P=0.48, I ²=93%). There was a high risk of heterogeneity, partly due to the discrepant discharging criteria among different institutions (Fig. 7C).

Overall cardiovascular complications

Six studies incorporating 2744 procedures26,29,31–33,35 investigated the incidence of overall cardiovascular complications, which was higher in the α-blockade pretreatment group, but the difference was not statistically significant: RR=2.06 (0.71, 5.97) (P=0.18, I ²=66%) (Fig. 7D).

Mortality

No short-term mortality was noted in all studies, but two. Boutros et al.22 reported one patient died of intracranial metastatic tumor, Liu et al.35 reported two deaths due to hemorrhagic shock caused by massive intraoperative bleeding and aspiration of regurgitation, respectively. None of the deaths was inferred to be associated with preoperative treatment.

Sensitivity analysis

Sensitivity analysis was performed for pooled outcomes with high risk of statistical heterogeneity identified by the I ² test. For the comparison of minimum systolic blood pressure, the exclusion of the study by Liu et al.29 that only include open surgeries resulted in a similar overall effect estimate but a significantly reduced statistical heterogeneity: MD=0.21 (−2.76, 3.18) mmHg (P=0.89, I ²=0%).

The analyses showed no remarkable changes in the effect estimate with the sequential exclusion of each study from the analysis (Fig. 8). Besides, the exclusion of studies with serious overall risk of bias yielded similar pooled estimates of intraoperative minimum systolic blood pressure: MD=−8.49 (−23.12, 6.15) (P=0.26, I ²=92%) and postoperative length of stay: MD=0.76 (−1.28, 2.79) days (P=0.47, I ²=95%).

Figure 8.

Sensitivity analysis of effect estimates. Minimum systolic blood pressure (A) and length of stay (B).

Discussion

This systematic review and meta-analysis updated the previous study by Schimmack et al 37. They found no beneficial efficacy for α-blockade pretreatment in surgery for pheochromocytoma versus no blockade. For the scarcity of eligible studies, their conclusion was based upon only two outcomes of intraoperative maximum blood pressure and highest heart rate. Considering a comprehensive assessment of the bi-directionality and intensity of hemodynamic fluctuations. We incorporated more parameters to evaluate its effect on hypertensive and hypotensive episodes. Besides, data on major perioperative events and cardiovascular morbidity were initially investigated to ulteriorly reveal patients’ clinical outcomes. Our result demonstrated no beneficial efficacy of α-blockade on stabilizing intraoperative hemodynamics for PPGL resections. Although α-blockade pretreatment was associated with more prolonged hypotension and vasopressor usage than no blockade, perioperative cardiovascular morbidity remained comparable with no blockade.

Nonselective phenoxybenzamine is the first choice among α-blockers used for PPGL patients, which blocks α1 and α2-adrenergic receptors irreversibly to achieve a long-lasting effect38. However, phenoxybenzamine-related complications became the initiating element for abstaining α-blockade pretreatments, such as orthostatic hypotension, reflex tachycardia, and dizziness22,39. Besides, high cost and limited availability in certain regions also hampered its use15. Kuo et al.36 went through a nationwide database in the USA and found a significant shift-away trend from phenoxybenzamine to selective α-blockers and calcium channel blockers in the past decade, likely due to reduced costs, similar length of stay, and ICU admission. Our meta-analysis also demonstrated a higher risk of prolonged hypotension episodes necessitating vasopressor usage associated with preoperative α-blockade. This might be attributed to α1-adrenoceptor irreversibly blocked by phenoxybenzamine that remained irresponsive to normal catecholamines stimulation. Selective α-blockades such as doxazosin, prazosin, and terazosin may be alternatives, however, a recent meta-analysis revealed the inferiority of selective α-blockades in preventing intraoperative blood pressure fluctuations compared with phenoxybenzamine, despite the comparable risk of perioperative morbidity40.

Although tumor size and urine metanephrine levels were found to be associated with intraoperative blood pressure fluctuations, risk factors that precisely predict HDI are still undetermined14,41. The reported incidence of intraoperative HDI remained as high as 40–70% in PPGL patients despite adequate α-blockade pretreatment11–13,42. It was inferred that intraoperative hemodynamic fluctuations were mainly caused by the sudden release and retreat of catecholamines due to tumor manipulation and removal, hardly to be blocked by any preoperative medication43. Moreover, intraoperative HDI rarely leads to major postoperative events. The overall cardiovascular morbidity has fallen to 3–5%, and perioperative mortality was even close to zero in contemporary series5. In contrast, vigorous monitoring and application of various fast-acting vasoactive agents allow anesthesiologists to take control of hemodynamic fluctuations promptly13,44. It is rational to argue that, in most cases, intraoperative HDI episodes should no longer be considered extremely dangerous or even catastrophic events as they once were.

With the development of diagnostic imaging, more pheochromocytomas are diagnosed as incidentalomas rather than symptomatic. Normotensive pheochromocytomas account for up to 40% of incidental adrenal tumors detected on imaging45 and 23–55% of total pheochromocytoma patients46. Compared with hypertensive PPGL, normotensive tumors demonstrated a quite distinct catecholamines secretion pattern with a significantly higher proportion of dopamine, rather than biologically negative43, calcium channel blockers might be an optimal pretreatment regimen in those patients for minimized risk of hypotension and reflex tachycardia47. Subgroup analysis regarding normotensive PPGLs in this meta-analysis yielded a consistent result with general PPGL participants, indicating that prudent omission of α-blockade pretreatment is safe and feasible for those patients.

The patterns of PPGL perioperative management shifted vastly in the past few decades. Multidisciplinary involvements, especially efforts of anesthetic interventions, achieved a great reduction of overall surgical risk and mortality. In contrast, however, more confounding factors were introduced to studies focusing on a single preoperative intervention like α-blockade. For instance, the application of various quick-acting vasoactive agents allows anesthesiologists to correct HDI promptly, which might to some extent compensate for the potential risk of inadequate preoperative preparation. Moreover, patients with hormone-functioning PPGL usually manifest refractory hypertension and cardiovascular comorbidities. Other antihypertensives and vasoactive drugs (calcium channel blockers, β-blockers, etc.) may be indicated as per specific preoperative preparation criteria, regardless of whether they were α-blockaded or not, which may also interfere with the actual efficacy of α-blockade.

There are certain limitations in our study. First, the absence of data from RCTs resulted in a reduced level of evidence regarding our findings, despite the various factors discussed thoroughly previously that impede high-quality RCTs on this topic28,37. Besides, the exact range or dividing values of blood pressure to define intraoperative HDI remain undetermined. We complied with the predefined thresholds to evaluate the overall incidence of intraoperative HDI but might as well neglect its variability.

Therefore, the result of this meta-analysis should not be interpreted as an assertion that α-blockade can be safely omitted without considerations of patient status and institutional expertise, but as a critical appraisal against the adherence to a dogmatic preparation paradigm, which is cumbersome, expensive, and without evident benefits.

Conclusions

This systematic review and meta-analysis showed no beneficial effects of α-blockade pretreatment on intraoperative hemodynamics as well as perioperative morbidity and mortality over no blockade, both in hypertensive and normotensive PPGL patients. However, multicenter RCTs are still warranted for further verification.

Ethical approval

No ethical approval was given since it is not applicable for a meta-analysis.

Sources of funding

This work was supported by grants from the Chongqing Municipal Health Commission (2020jstg018).

Author contribution

D.W.: supervision, project administration, and funding acquisition. J.W.: conceptualization, methodology, and writing – original draft preparation. Q.L.: data curation and formal analysis. S.J.: data curation and software. J.Z.: writing – review and editing. J.H.: validation. Y.L.: visualization.

Conflicts of interest disclosure

The authors declare that they have no financial conflict of interest with regard to the content of this report.

Research registration unique identifying number (UIN)

1. Name of the registry: PROSPERO database.

2. Unique Identifying number or registration ID: CRD42022370263.

3. Hyperlink to your specific registration (must be publicly accessible and will be checked):https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022370263

Guarantor

Delin Wang.

Data availability statement

Data sharing is not applicable to this study as no original data were created or analyzed in this study.