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The use of low-dose epinephrine in hand surgery has made it possible to perform a wide range of surgical procedures in the office setting. Low-dose epinephrine use is safe, and its vasoconstrictive effects are reversible with phentolamine. In this report, we present late-onset finger ischemia beginning 3 hours after an ipsilateral carpal tunnel and A1 pulley release of the middle finger anesthetized with local anesthetic and low-dose epinephrine (1:100,000). Finger ischemia lasted 14 hours until rescued with phentolamine injection., (Copyright © 2017 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Background: Phentolamine mesylate (PM) is widely used to reverse local anesthesia after dental procedures. Limited knowledge is available regarding effectiveness and safety in routine dental practice., Methods: The authors conducted 2 national, prospective, noninterventional, postauthorization effectiveness studies (OraVerse Post-Authorization Efficacy Study [ORAPAES] controlled, OraVerse Non-Interventional Study [ORANIS] uncontrolled) in patients receiving a local anesthetic as part of their dental treatment. They investigated time to recovery of normal sensation and function and the frequency of adverse events (AEs). The authors used Kaplan-Meier methods to analyze times to recovery; in ORAPAES, they used hazard ratios based on Cox models using the control group as a reference., Results: In ORAPAES (n = 856), PM reduced the time to recovery of normal sensation and function with a difference in the median time of 70 and 79 minutes, respectively, with similar results observed in ORANIS (n = 445). In ORAPAES, patients in the PM group had, at any time point, a 2.77-fold higher chance of recovery to normal sensation (hazard ratio, 2.77; 95% confidence interval [CI], 2.35-3.26; P < .001) and for normal function 2.94-fold higher chance of recovery to normal sensation (95% CI, 2.49-3.47; P < .001) than in the control group. The observed incidence of AEs with PM treatment was 8.4% in ORAPAES (95% CI, 6.2-10.9) and 9.7% (95% CI, 7.1-12.7) in ORANIS. No serious AEs occurred., Conclusions: PM substantially reduced the time to recovery of normal sensation and function after local anesthesia in routine dental treatment. The results confirm the effectiveness, safety, and tolerability of PM used in patients with routine dental conditions in Germany, and that PM augments the safety of dental treatments., Practical Implications: The authors determined that PM is well suited to reverse local anesthesia after routine dental procedures., (Copyright © 2017 American Dental Association. Published by Elsevier Inc. All rights reserved.)

Background: Knowing that patients desire reduced duration of local anesthesia, the authors performed a meta-analysis to evaluate the efficacy of phentolamine mesylate (PM) in reducing anesthesia duration and the occurrence of adverse effects., Types of Studies Reviewed: The authors searched studies in 4 electronic databases up to December 18, 2014. For each study, the methodological quality was assessed according to the Cochrane Collaboration's tool for assessing risk of bias. Randomized controlled trials (RCTs) that used PM met the inclusion criteria., Results: Six RCTs met the inclusion criteria and were used to carry out a meta-analysis of the effectiveness of PM and a qualitative analysis of its adverse effects. The use of PM was more effective in reversing the anesthetic effect on the lower lip and tongue than was applying a placebo. Adverse effects reported in the studies were not statistically significant, the most frequent being headache, pain during injection, and postprocedure pain., Conclusions and Practical Implications: Based on limited evidence, PM is effective in reducing the persistence of anesthesia duration on the lower lip and tongue, with infrequent adverse effects of little clinical significance., (Copyright © 2015 American Dental Association. Published by Elsevier Inc. All rights reserved.)

Neurogenic pulmonary edema (NPE) is a clinical syndrome characterized by the acute onset of pulmonary edema following a significant CNS insult. The cause is believed to be a surge of catecholamines that results in cardiopulmonary dysfunction. Although there are myriad case reports describing CNS events that are associated with this syndrome, few studies have identified specific treatment modalities. We present a case of NPE caused by an intracranial hemorrhage from a ruptured arteriovenous malformation. We uniquely document a rise and fall of serum catecholamine levels correlating with disease activity and a dramatic clinical response to IV phentolamine.

Background: The authors conducted two multicenter, randomized, double-blinded, controlled Phase III clinical trials to study the efficacy and safety of phentolamine mesylate (PM) in shortening the duration and burden of soft-tissue anesthesia. The study involved 484 subjects who received one of four commercially available local anesthetic solutions containing vasoconstrictors for restorative or scaling procedures., Methods: On completion of the dental procedure, subjects randomly received a PM or a sham injection (an injection in which a needle does not penetrate the soft tissue) in the same site as the local anesthetic injection. The investigators measured the duration of soft-tissue anesthesia by using standardized lip- and tongue-tapping procedures every five minutes for five hours. They also evaluated functional measures and subject-perceived altered function, sensation, appearance and safety., Results: Median recovery times in the lower lip and tongue for subjects in the PM group were 70 minutes and 60 minutes, respectively. Median recovery times in the lower lip and tongue for subjects in the sham group were 155 minutes and 125 minutes, respectively. Upper lip median recovery times were 50 minutes for subjects in the PM group and 133 minutes for subjects in the sham group. These differences were significant (P < .0001). Recovery from actual functional deficits and subject-perceived altered function, sensation and appearance also showed significant differences between the PM and the sham groups., Conclusions: PM was efficacious and safe in reducing the duration of local anesthetic- induced soft-tissue numbness and its associated functional deficits., Clinical Implications: Clinicians can use PM to accelerate reversal of soft-tissue anesthesia and the associated functional deficits.

Background: The authors evaluated the safety and efficacy of a formulation of phentolamine mesylate (PM) as a local anesthesia reversal agent for pediatric patients., Methods: A total of 152 pediatric subjects received injections of local anesthetic with 2 percent lidocaine and 1:100,000 epinephrine before undergoing dental procedures. The authors then randomized subjects to receive a PM injection or a control injection (sham injection in which a needle does not penetrate the tissue) in the same sites as the local anesthetic was administered in a 1:1 cartridge ratio after the procedure was completed. Over a two- to-four-hour period, they measured the duration of soft-tissue anesthesia and evaluated vital signs, pain and adverse events., Results: The median recovery time to normal lip sensation was 60 minutes for the subjects in the PM group versus 135 minutes for subjects in the control group. The authors noted no differences in adverse events, pain, analgesic use or vital signs, and no subjects failed to complete the study., Conclusions: PM was well-tolerated and safe in children 4 to 11 years of age, and it accelerated the reversal of soft-tissue local anesthesia after a dental procedure in children 6 to 11 years of age., Clinical Implications: PM can help dental clinicians shorten the post-treatment duration of soft-tissue anesthesia and can reduce the number of posttreatment lip and tongue injuries in children.

Purpose: To examine prospectively the incidence of digital infarction and phentolamine rescue in a large series of patients in whom local anesthesia with adrenaline was injected electively into the hand and fingers. There continues to be a commonly held belief that epinephrine injection is contraindicated in the finger despite a lack of valid evidence to support this concept in the literature., Methods: From 2002 to 2004 there were 9 hand surgeons in 6 cities who prospectively recorded each consecutive case of elective hand and finger epinephrine injection. They recorded each instance of skin or tissue loss and the number of times phentolamine reversal of adrenaline vasoconstriction was required., Results: There were 3,110 consecutive cases of elective injection of low-dose epinephrine (1:100,000 or less) in the hand and fingers and none produced any instance of digital tissue loss. Phentolamine was not required to reverse the vasoconstriction in any patients., Conclusions: The true incidence of finger infarction in elective low-dose epinephrine injection into the hand and finger is likely to be remote, particularly with the possible rescue with phentolamine.

Background: Radial artery (RA) conduits are prone to early vasospasm. Current intraoperative treatment with papaverine fails to inhibit postoperative RA constriction. Pretreatment with topical a-antagonist solutions can inhibit RA vasoconstriction and cause dilatation for a longer period than achieved with papaverine., Methods: In 10 patients undergoing myocardial revascularization, the radial artery was harvested as a skeletonized vessel. A composite graft with reverse free RA on an in situ left internal thoracic artery was prepared before construction of distal coronary anastomoses. The RA pedicle was then put in a small syringe filled with Regitine (phentolamine methansulphonic, 0.07 mg/mL) ("Jacuzzi") and warmed by immersing the container in a warm saline bath for 8 to 15 minutes. The RA free flow was measured before and after topical treatment with Regitine., Results: The mean number of grafts per patient was 2.9 (range 2 to 4). The mean number of radial anastomoses was 1.8 per patient. Left internal thoracic artery free flow was 110 +/- 29 mL/min. Regitine increased radial free flow from 49 +/- 35 to 77 +/- 30 mL/min (p < 0.01). Five patients underwent postoperative coronary angiography. All radial anastomoses were patent., Conclusions: Topical treatment of RA with Regitine increases RA free flow and is an effective intraoperative means of decreasing RA spasticity.

Severe hypertension is a common clinical problem in the United States, encountered in various clinical settings. Although various terms have been applied to severe hypertension, such as hypertensive crises, emergencies, or urgencies, they are all characterized by acute elevations in BP that may be associated with end-organ damage (hypertensive crisis). The immediate reduction of BP is only required in patients with acute end-organ damage. Hypertension associated with cerebral infarction or intracerebral hemorrhage only rarely requires treatment. While nitroprusside is commonly used to treat severe hypertension, it is an extremely toxic drug that should only be used in rare circumstances. Furthermore, the short-acting calcium channel blocker nifedipine is associated with significant morbidity and should be avoided. Today, a wide range of pharmacologic alternatives are available to the practitioner to control severe hypertension. This article reviews some of the current concepts and common misconceptions in the management of patients with acutely elevated BP.

The use of phentolamine (Regitine) as a specific competitive antagonist of epinephrine by virtue of its alpha-blocking properties is well known. Its use via digital nerve block infiltration has been described in cases of IV infiltration of sympathomimetics. We discuss a recent case of local and direct infiltration of phentolamine along the course of the digital arteries and directly into the thumb tuft to reverse the local ischemic effects of epinephrine.

Although uncommon, hypertensive crisis must be recognized properly and quickly so that immediate treatment can be instituted to prevent serious and irreversible complications. It is important to bear in mind that it is not necessarily the absolute level of hypertension that signals impending danger but the function of an affected target organ such as the heart or kidneys that allows the physician to make the diagnosis of hypertensive crisis. There are a variety of potent antihypertensive drugs that can lower the blood pressure promptly, but the choice must be based on careful clinical and hemodynamic assessment of the patient. The goal is to lower the blood pressure and to stabilize or improve the target organ function without causing underperfusion.

We have assessed the benefit of separate or combined alpha- and beta-receptor blockade in the treatment of 33 patients suffering from acute (less than 48 hr) myocardial infarction complicated by sustained (greater than 6 hr) systolic hypertension (systolic blood pressure greater than 150 mm Hg). Eight patients have been treated with metoprolol, 7 with phentolamine and 18 with labetalol. We evaluated the effects of these drugs on hemodynamics and arterial and mixed venous blood gases. The patients were divided into two groups on the basis of the pulmonary wedge pressure. The first group had a pressure greater than 15 mm Hg. It included 9 patients treated with labetalol (1.8 mg/min for 1 hr) and 7 others with phentolamine (0.6 mg/min for 1 hr). The wedge pressure in the second group was less than 13 mm Hg. Nine patients in this group had been treated with labetalol (2.1 mg/min for 1 hr) and 8 others with metoprolol (0.2 mg/kg in 15 min). Labetalol normalized the blood pressure in both groups within 1 hr as did phentolamine. Metoprolol did not significantly reduce either the systolic or the diastolic pressures. The high wedge pressures in the first group were reduced by both labetalol and phentolamine. The cardiac index was increased following phentolamine administration while it was reduced by labetalol. In the group with low wedge pressure, labetalol and metoprolol induced a slight but significant reduction in cardiac index but the pulmonary wedge pressures were significantly increased for metoprolol only. The rate-pressure product was very significantly decreased by labetalol and metoprolol but not by phentolamine. The emergency treatment of systemic hypertension occurring in the setting of acute myocardial infarction would thus appear to be best achieved by combined alpha- and beta-blockade rather than with either pure alpha- or pure beta-blockade. Phentolamine, however, would be a good drug in the presence of a reduced cardiac index.

Therapy with phentolamine can improve the condition of patients with congestive heart failure due to the inotropic effect of this drug, as well as its vasodilating action. The use of oral therapy with phentolamine has not been adequately investigated in patients with chronic heart failure. Therefore, nine patients with chronic heart failure due to underlying valvular disease received 50 mg of phentolamine four times a day for two weeks. Echocardiograms and measurements of systolic time intervals were obtained prior to administration of phentolamine and two weeks after the introduction of therapy with the drug. As a result of therapy with phentolamine, the ejection fraction, the percentage of change in the minor axis, and the velocity of circumferential fiber shortening significantly increased, while the left atrial dimension decreased. Therapy with phentolamine produced a significant decrease in the preejection period index, as well as the ratio of the preejection period over the left ventricular ejection time. Thus, oral therapy with phentolamine improves left ventricular function in patients with chronic heart failure.

This study evaluates the role of early renal vasoconstriction in the pathogenesis of mercuric chloride (HgCl2)-induced acute renal failure (ARF) in the dog. Within 3 hr after mercury, glomerular filtration rate (GFR), from 45 +/- 4 25 +/- 2 ml/min, and renal blood flow (RBF), from 268 +/- 22 to 161 +/- 19 ml/min, decreased simultaneously. A rise in diuresis and urinary solute excretion occurred. Morphological and functional studies excluded a major role for tubular leakage or obstruction. An attempt was made to prevent the early renal vasoconstriction, by the administration of Haemaccel, a plasma volume expander, alone or in combination with phentolamine. In both settings the fall in RBF after mercury was prevented. Haemaccel volume expansion alone provoked a significant rise in GFR before HgCl2, but the GFR fell by 29% 3 hr after HgCl2. The Haemaccel/phentolamine combination had no influence on pre-mercury GFR values. In this group, a decrease of GFR by 44% was noted 3 hr after mercury. In conclusion, changes in GFR and renal hemodynamics can be dissociated in the early phase of nephrotoxic ARF. The fall in GFR can be attributed either to a decrease in glomerular ultrafiltration capacity and/or changes in glomerular afferent and efferent resistances, leading to a decrease in glomerular hydrostatic pressure.

A study was made of the hemodynamic effects of levarterenol and phentolamine in patients in whom low cardiac output developed following open-heart operation. After the patients were weaned from cardiopulmonary bypass, the inotropic agents were infused into an external or internal jugular vein through an IVAC pump. Levarterenol was administered first until systolic arterial pressure rose 20 to 30% above the higest recorded preoperative pressure. After stabilization, phentolamine was administered, and infusion rates were adjusted so that arterial blood pressure was returned to levels measured before bypass. After infusion, all patients showed an increase in cardiac index, mean arterial pressure, mean stroke volume index, and left ventricular stroke work index. Mean pulmonary artery pressure, pulmonary vascular resistance, and left atrial pressure decreased in all patients. This study demonstrates that hemodynamic improvement occurs in humans in low cardiac output state with simultaneous infusion of levarterenol and phentolamine. We recommend these agents for use in patients with low output, unless they continue to receive propranolol during and after operation. Patients on a regimen of propranolol should not be given levarterenol and phentolamine.