Comparison of Preoperative Alpha-blockade for Resection of Paraganglioma and Pheochromocytoma.

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.

Hydromorphone Unit Dose Affects Intraoperative Dosing: An Observational Study.

BACKGROUND: Although clinical factors related to intraoperative opioid administration have been described, there is little research evaluating whether administration is influenced by drug formulation and, specifically, the unit dose of the drug. The authors hypothesized that the unit dose of hydromorphone is an independent determinant of the quantity of hydromorphone administered to patients intraoperatively. METHODS: This observational cohort study included 15,010 patients who received intraoperative hydromorphone as part of an anesthetic at the University of California, Los Angeles hospitals from February 2016 to March 2018. Before July 2017, hydromorphone was available as a 2-mg unit dose. From July 1, 2017 to November 20, 2017, hydromorphone was only available in a 1-mg unit dose. On November 21, 2017, hydromorphone was reintroduced in the 2-mg unit dose. An interrupted time series analysis was performed using segmented Poisson regression with two change-points, the first representing the switch from a 2-mg to 1-mg unit dose, and the second representing the reintroduction of the 2-mg dose. RESULTS: The 2-mg to 1-mg unit dose change was associated with a 49% relative decrease in the probability of receiving a hydromorphone dose greater than 1 mg (risk ratio, 0.51; 95% CI, 0.40-0.66; P < 0.0001). The reintroduction of a 2-mg unit dose was associated with a 48% relative increase in the probability of administering a dose greater than 1 mg (risk ratio, 1.48; 95% CI, 1.11-1.98; P = 0.008). CONCLUSIONS: This observational study using an interrupted time series analysis demonstrates that unit dose of hydromorphone (2 mg vs. 1 mg) is an independent determinant of the quantity of hydromorphone administered to patients in the intraoperative period.

A novel factor influencing perioperative midazolam administration: The effect of presentation dose on administration dose.

BACKGROUND AND AIMS: Determinants of pharmaceutical unit presentations are not well understood and often appear indiscriminate. However, the dose administered may play a key role in the patient's anesthetic course. A recent change in a pharmaceutical vendor at our institution resulted in a change in midazolam presentation. In this study, we sought to determine whether the dose in which midazolam was dispensed to anesthesiologists was associated with the quantity of midazolam administered perioperatively. MATERIAL AND METHODS: In this retrospective, observational study, we examined 310 adult patients who underwent general anesthesia at a single site, tertiary care, university hospital before and after a change in midazolam presentation from 2 mg to 3 mg. The primary outcome was the quantity of midazolam administered during the anesthetic. Additional clinical variables measured included patient age, weight, gender, and American Society of Anesthesiology (ASA) classification. RESULTS: The mean dose of midazolam administered to the 3 mg presentation cohort was 2.67 mg compared to 1.99 mg to the 2 mg presentation cohort (mean difference: 0.68 mg, 95% CI: 0.46-0.9 mg; P value <0.001). According to a logistic regression model, the odds of receiving a dose of 3 mg or greater in the 3 mg presentation cohort was 22 times greater than the odds of receiving such a dose in the 2 mg presentation cohort (OR: 22.3; 95% CI: 10.6-47.0; P < 0.001). This effect of presentation dose on administration dose was not observed in patients greater than or equal to 65 years of age. CONCLUSIONS: Midazolam presentation dose influences the administration dose.

Transient Intraoperative Central Diabetes Insipidus in Moyamoya Patients Undergoing Revascularization Surgery: A Mere Coincidence?

We present 2 patients with Moyamoya disease undergoing revascularization surgery who developed transient intraoperative central diabetes insipidus with spontaneous resolution in the immediate postoperative period. We speculate that patients with Moyamoya disease may be predisposed to a transient acute-on-chronic insult to the arginine vasopressin-producing portion of their hypothalamus mediated by anesthetic agents. We describe our management, discuss pertinent literature, and offer possible mechanisms of this transient insult. We hope to improve patient safety by raising awareness of this potentially catastrophic complication.

Transient increases in intraoperative parathyroid levels related to anesthetic technique.

BACKGROUND: Parathyroid hormone (PTH) secretion is partially regulated by circulating catecholamines. We examined the effect of different anesthetic techniques on intraoperative PTH (IOPTH) levels in patients undergoing parathyroidectomy for primary hyperparathyroidism. METHODS: We prospectively studied 132 patients divided into 3 anesthetic cohorts: monitored anesthetic care (MAC; n = 45), general anesthesia with laryngeal mask airway (LMA; n = 43), or general endotracheal anesthesia (GETA; n = 39). IOPTH levels were drawn before induction and at defined intervals postinduction. RESULTS: All anesthetic techniques increased IOPTH levels from preinduction to 3 minutes postinduction (MAC, 28%; LMA, 45%; GETA, 65%; P < .001). Temporal trends in postinduction IOPTH levels were similar in patients receiving general anesthesia, characterized by a peak effect at 6 minutes. Using a multivariate logistic regression analysis, GETA was >7 times more likely to increase the preinduction IOPTH by ≥ 50% at 3 minutes postinduction compared with MAC (P < .0001). Using immediate postinduction IOPTH levels in surgical decision making would have led to failed surgery in 2 of 6 patients with multiple gland disease receiving GETA. CONCLUSION: Preincision IOPTH samples should be drawn before induction to avoid incorporation of potentially misleading anesthetic-related IOPTH elevations into surgical decision making.

A selective, Bayesian approach to intraoperative PTH monitoring.

OBJECTIVE: To determine if the performance of intraoperative parathyroid hormone monitoring (IPM) can be optimized by limiting its application to patients with weak preoperative localization. BACKGROUND: The value of IPM during minimally invasive parathyroidectomy (MIP) has been questioned, particularly in cases with strong preoperative localization. We describe a novel, Bayesian strategy employing IPM in select patients with a high pretest probability of multiple gland disease (MGD). METHODS: We prospectively examined 361 consecutive patients undergoing surgery for primary hyperparathyroidism. All patients underwent sestamibi (MIBI) scanning and surgeon-performed ultrasound. Intraoperative PTH levels were only used for surgical decision-making in the MIBI-negative, ultrasound-positive patient subset. The following outcomes were analyzed: MGD rate, test performance, success rate, and operative time. RESULTS: Patients with any positive localization study (91%) were offered MIP. The success rate was 99%. The MGD rate was 3% in MIBI-positive patients and 36% in MIBI-negative patients (10% overall, P < 0.0001). MIBI and surgeon-performed ultrasound were equally sensitive (80% vs. 85%, NS). Among MIBI-negative patients, 71% of whom underwent MIP with IPM, an inadequate fall in the 10-minute postexcision PTH level was highly predictive of MGD, saving 10 failures while causing 1 inappropriate conversion to bilateral exploration (negative likelihood ratio, NLR 28.0). In contrast, among MIBI-positive patients, IPM could have saved 3 failures at the expense of 18 inappropriate conversions (NLR 9.9). IPM increased operative time from 34 to 60 minutes (P < 0.0001). CONCLUSION: IPM is more likely to guide the surgeon correctly when used only in MIBI-negative patients, who have a high pretest probability of MGD. This selective strategy maintains high success rates while limiting the frequently adverse impact that IPM carries when used indiscriminately.