Topical Nitroglycerin Research Articles

Invited commentary

Invited commentary

A Randomized Controlled Trial Comparing Topical Nitroglycerin to Sphincterotomy in the Treatment of Chronic Anal FissuresLimited Project Grant #059

A Randomized Controlled Trial Comparing Topical Nitroglycerin to Sphincterotomy in the Treatment of Chronic Anal FissuresLimited Project Grant #059

Rectogesic® (glyceryl trinitrate 0.2%) ointment relieves symptoms of haemorrhoids associated with high resting anal canal pressures

Some haemorrhoids are associated with high resting anal canal pressures. The aim of this study was to assess if Rectogesic, a topical glyceryl trinitrate 0.2% ointment was effective in relieving symptoms of early grade haemorrhoids associated with high resting anal canal pressures. This was a prospective, two-centre, open label study of 58 patients with persistent haemorrhoidal symptoms. Patients with first or second degree haemorrhoids and a maximum resting anal canal pressure > 70 mmHg were included. Rectogesic was applied three times a day for 14 days. Anorectal manometry was performed 30 min after the first application of Rectogesic. A 28-day diary was completed during 14 days of therapy and for 14 days after cessation of treatment. This recorded the incidence of rectal bleeding, and visual analogue scales for anal pain, throbbing, pruritus, irritation and difficulty in bowel movement. Maximum resting anal canal pressures were reduced after application of Rectogesic (115.0 +/- 40.4 mmHg vs 94.7 +/- 34.1 mmHg, P < 0.001). In the study period and at 14 days after cessation of Rectogesic, there was significant reduction in rectal bleeding (P = 0.0002), and significant improvement of anal pain (P = 0.0024), throbbing (P = 0.0355), pruritus (P = 0.0043), irritation (P = 0.0000) and difficulty in bowel movement (P = 0.001). The main adverse event was headache in 43.1% of patients. Rectogesic is a safe and feasible treatment for patients with early grade haemorrhoids associated with high resting anal canal pressures.

Botulinum Toxin vs. Topical Glyceryl Trinitrate Ointment for Pain Control in Patients Undergoing Hemorrhoidectomy: A Randomized Trial

The maximum resting pressure in the anal canal is greatly raised after hemorrhoidectomy. This increase is likely to be the cause of postoperative pain, which is still the most troublesome early problem after hemorrhoidectomy. This study was designed to compare, after hemorrhoidectomy, the effects of intrasphincter injection of botulinum toxin vs. application of glyceryl trinitrate ointment in improving wound healing and reducing postoperative pain at rest or during defecation. Thirty patients with hemorrhoids of third and fourth degree were included in the study and randomized in two groups. Anorectal manometry was performed preoperatively and 5 and 40 days after hemorrhoidectomy. One group received one injection containing 20 IU of botulinum toxin, whereas the other an application of 300 mg of 0.2 percent glyceryl trinitrate ointment three times daily for 30 days. Five days after hemorrhoidectomy, maximum resting pressure was significantly reduced compared with baseline values in both groups (85 +/- 15 vs. 68 +/- 11 mmHg for the group treated with botulinum toxin, 87 +/- 11 vs. 78 +/- 11 mmHg for the group treated with glyceryl trinitrate ointment). Overall analysis of postoperative pain at rest showed a significant reduction in the botulinum toxin group vs. glyceryl trinitrate group, whereas pain during defecation and time of healing were similar. Adverse effects, such as headaches, were observed only in the glyceryl trinitrate group. Forty days after hemorrhoidectomy in the glyceryl trinitrate group, maximum resting pressure values were similar to preoperative ones, whereas the values were still reduced in the botulinum toxin group. A single intrasphincter injection of botulinum toxin was more effective and safer than repeated applications of glyceryl trinitrate in reducing early postoperative pain at rest but not during defecation.

Efficacy and Safety of Botulinum Toxin A Injection Compared with Topical Nitroglycerin Ointment for the Treatment of Chronic Anal Fissure: A Prospective Randomized Study

To evaluate the efficacy and safety of botulinum toxin A injection compared with topical nitroglycerin ointment for the treatment of chronic anal fissure (CAF). Fifty outpatients with CAF were randomized to receive either a single botulinum toxin injection (30 IU Botox) or topical nitroglycerin ointment 0.2% b.i.d. for 2 wk. If the initial therapy failed, patients were assigned to the other treatment group for a further 2 wk. If CAF still showed no healing at wk 4, patients received combination therapy of botulinum toxin and nitroglycerin for 4 additional wk. Persisting CAF at wk 8 was treated according to the investigator's decision. Healing rates, symptoms, and side effects of the therapy were recorded at wk 2, 4, 8, 12, and 24 after randomization. The group initially treated with nitroglycerin showed a higher healing rate of CAF (13 of 25, 52%) as compared with the botulinum toxin group (6 of 25, 24%) after the first 2 wk of therapy (p < 0.05). At the end of wk 4, CAF healed in three additional patients, all receiving nitroglycerin after initial botulinum toxin injection. Mild side effects occurred in 13 of 50 (26%) patients, all except one were on nitroglycerin. Nitroglycerin ointment was superior to the more expensive and invasive botulinum toxin injection for initial healing of CAF, but was associated with more but mild side effects.

Diffuse and Severe Ischemic Injury of the Extremities: A Complication of Umbilical Vein Catheterization

We report a case of severe, peripheral, and diffuse tissue ischemia after umbilical vein catheterization (UVC) in a preterm newborn born to a preeclamptic mother. Nitroglycerin ointment was used to treat lesions. The recovery was good but partial loss of the distal phalange of one finger and one toe occurred. This is the first report of peripheral vasospasm occurring after UVC. Topical nitroglycerin, traditionally used to treat peripheral artery catheter-induced ischemic injury, may be useful to treat the same lesions occurring after UVC.

Allergic and nonallergic reactions to nitroglycerin

Allergic and nonallergic reactions to nitroglycerin occur. The aims of this study were to review the different manifestations of nitroglycerin allergy, to explain how to evaluate for it, and to discuss its treatment. We reviewed relevant literature in peer-reviewed journals, computerized databases, and references identified from relevant bibliographics. Nitroglycerin's most common side effects are headache, facial flushing, head throbbing, fainting, hypotension, tachycardia, and syncope. The majority of reported skin reactions to topical and transdermal nitroglycerin products are irritant contact dermatitis, allergic contact dermatitis, and urticaria. Five cases of presumed allergic reactions to oral, sublingual, intravenous, or perianal nitroglycerin products have been described. Patch testing may be helpful in subjects with skin reactions to topical or transdermal nitroglycerin. In subjects with positive patch tests to nitroglycerin (allergic contact dermatitis), transdermal nitroglycerin patches and other topical nitroglycerin products should be avoided. Most patients with contact dermatitis to nitroglycerin have tolerated oral nitroglycerin, sublingual nitroglycerin, or oral isosorbide challenges.

Controlled Dose Delivery in Topical Treatment of Anal Fissure: Pilot Study of a New Paradigm

Topical nitroglycerin has been widely used as a means for avoiding surgery in patients with anal fissure. However, nitroglycerin has not been universally accepted for this application because of inconsistency of efficacy and side effects. This study compares conventional digital application with precise intra-anal dosing of nitroglycerin using a specialized dose-delivery device and anal cannula. Twenty-six consecutive patients (13 males) with chronic anal fissure and no previous treatment were randomly allocated to receive 0.75 ml of 0.3 percent nitroglycerin ointment (2.25 mg nitroglycerin) t.i.d. intra-anal using the cannula (Group A) or perianally with the gloved finger (Group B). Nitroglycerin dosage was controlled in Group A by the dose-delivery device connected to the cannula and by single-dose preloaded syringes in Group B. Anal manometry: pressure reduction after application of nitroglycerin was 47 +/- 18.6 in Group A and 20.7 +/- 13.4 percent in Group B (P < 0.01). Headaches were reported by 1 of 10 patients in Group A and 10 of 12 patients in Group B (P = 0.0027). Seven patients of Group B had to be crossed to intra-anal treatment as a result of intensity of headaches. Pain relief was noted by 8 of 10 and 9 of 12 patients in Groups A and B, respectively (P = 0.6). Sphincterotomy was required in only 13.6 percent of all patients. Controlled intra-anal dosing of topical nitroglycerin produces a significantly greater reduction in sphincteric pressure and lower incidence of headaches than with perianal administration of the same dose of ointment. These results suggest a new paradigm for increasing safety and efficacy of dose-dependent prescription anal topical medications.

The use of therapeutic medications for soft‐tissue injuries in sports medicine

The use of non-steroidal anti-inflammatory drugs (NSAIDs) to treat most muscle, ligament and tendon injuries should be reassessed. They have, at best, a mild effect on relieving symptoms and are potentially deleterious to tissue healing. Soft-tissue injury associated with definite inflammatory conditions such as bursitis or synovitis or involving nerve impingement does warrant short-term treatment with NSAIDs. Paracetamol has similar efficacy to NSAIDs in soft-tissue injury, is cheaper, and has a lower side-effect profile. It is the analgesic of choice for most soft-tissue injury. Cyclo-oxygenase-2 (COX-2) inhibitors should not be used to treat soft-tissue injuries unless impingement is a major feature and non-selective NSAIDs are contraindicated (eg, coexisting gastric disorder), and the patient is not at cardiovascular risk. Corticosteroid injections for tendon injuries may achieve a mild to moderate reduction in pain for up to 6 weeks. However, they do not promote tendon healing, so should generally be used only when healing is not a critical goal. Promising new therapeutic treatments for soft-tissue injuries include topical glyceryl trinitrate, aprotinin injections, and prolotherapy.

Comparison of Topical Glyceryl Trinitrate Ointment and Oral Nifedipine in the Treatment of Chronic Anal Fissure

This study was designed to compare the effect of topical glyceryl trinitrate (GTN) and oral nifedipine treatments on maximal anal resting pressure (MarP) and subsequently to assess their effectiveness in healing of chronic anal fissure (CAF). Patients were allocated randomly to receive either oral nifedipine retard (10 patients) 20 mg twice daily or instructed to apply glyceryl trinitrate (0.2 percent) ointment (10 patients) into the lower half of the anal canal twice daily. They were reviewed and assessed at the first visit and every fortnight for measurement of MARP, pain scores, blood pressure, pulse rate, healing of the fissure and adverse effects. Treatment were continued until healing had occurred or for up to 8 weeks. MARP values before and after application of the GTN ointment was 113.2 cm H2O and 72.5 cm H2O respectively (P < 0.001). Nifedipine caused a reduction in mean MARP from 105.2 to 74.0 cm H2O (P < 0.001). Linear analogue pain scores were significantly reduced after 2 weeks treatment with GTN and nifedipine (P < 0.001) and continued throughout the treatment period. At the end of the study; 7 of the 10 patients in the GTN group were deemed to be healed (5) or improved (2), compared with 6 of the 10 patients in the nifedipine group (5 healed, 1 improved). Headaches occurred in 3 patients in the GTN group, compared with one patient in the nifedipine group. There was no significant difference between GTN and nifedipine in terms of reduction in MARP and pain score, healing of the fissure and incidence of early recurrence and side effects of treatments. We conclude that GTN ointment and oral nifedipine are equally effective in the treatment of chronic anal fissure.

Resolution of peripheral tissue ischemia secondary to arterial vasospasm following treatment with a topical nitroglycerin device in two newborns: case reports

Resolution of peripheral tissue ischemia secondary to arterial vasospasm following treatment with a topical nitroglycerin device in two newborns: case reports

Topical glyceryl trinitrate in the treatment of chronic anal fissure.

The aetiology of anal fissure is unclear, but there is an association with high maximum resting pressure (MRP). Internal sphincterotomy reduces MRP and heals fissure through an increase in local blood supply. Glyceryl trinitrate (GTN) is a nitric oxide donor which contributes to internal anal sphincter relaxation via a non-adrenergic non-cholinergic pathway. GTN ointment was applied topically in different concentration to the anal margin in patients with chronic anal fissure to monitor its effect primarily on MRP and secondarily on fissure healing. Nineteen patients with chronic anal fissure were treated with ointment containing increasing concentrations of GTN (0.2-0.8 per cent) to produce a reduction in MRP of greater than 25 per cent. The actual dose of GTN varied as no standard delivery system has been developed, but a 'typical amount' of GTN ointment weighed about 200 mg. In 15 of 19 patients, a concentration greater than 0.2 per cent was required to lower the MRP by at least 25 per cent. The minimum concentration of GTN that reduced the resting pressure by at least 25 per cent was prescribed and local application was carried out by the patient twice daily for 6 weeks. At 6 weeks, nine patients had healed, six required sphincterotomy and four were lost to follow-up. Eight of the nine patients with healed fistula required a GTN concentration of 0.3 per cent or more. Sixteen patients were resistant to the usually effective does of 0.2 per cent GTN. In three there was tachyphylaxis and the duration of action of GTN was less than the 12 h described previously in control patients. Two patients did not fulfil the study because of headache.

Cost-Saving Effect of Treatment Algorithm for Chronic Anal Fissure: A Prospective Analysis

Evidence-based medicine suggests that in the management of chronic anal fissure (CAF), lateral internal sphincterotomy (LIS) is far more effective than medical treatment in lowering the anal sphincter tone and curing the fissure. In the current study, we developed a treatment algorithm from topical nitroglycerin (NTG) to botulinum toxin type A (Botox [BTX]) to LIS and analyzed its cost benefit by calculating the effective and potential costs based on the treatment success and the rate of avoided surgeries. Patients presenting between November 2003 and December 2004 with CAF and symptoms for greater than 3 months were prospectively treated according to a treatment algorithm which started with (1) topical NTG, in case of failure (2) injection of BTX, thus limiting (3) surgery to those who failed both nonsurgical options or at any point chose the surgical approach. Based on the primary end points of fissure healing or surgery, we calculated the true cost (algorithm) and the potential incremental cost (BTX plus surgery or surgery in all patients, respectively). Sixty-seven patients with CAF (25 men and 42 women; median duration of symptoms, 16 weeks) were treated according to the algorithm. NTG alone was successful in fissure healing in 31 of 67 patients (46.2%). Two developed a recurrent fissure and then received BTX as part of the protocol. Of the 36 patients who failed NTG trial, 3 requested surgery; the others were treated with BTX, which was successful in 84.8%. Five patients (15.2%) failed BTX and subsequently required surgery. The overall surgery rate in the whole study group was 11.9%, whereas CAF healed in 88.1% of our patients with medical treatment alone. Cost for NTG is $10; for 100 units BTX, $528; and for outpatient surgery, $1119. The total cost for these 67 patients therefore was $33,252 ($290 for NTG, $20,580 for NTG plus BTX, $3,357 for NTG plus LIS, and $9,025 for NTG plus BTX plus LIS). If all patients had received BTX with a 15% failure rate, the total cost would have been $56,688 (70.3% cost increase). If all patients had undergone surgery as initial/only treatment, the total cost would have been $74,973 (125% cost increase). Our treatment algorithm for CAF with stepwise escalation can avoid surgery in 88% of the patients. It is highly cost-efficient and resulted in savings of 41% (compared with BTX plus LIS) and up to 70% (compared with surgery in all patients), respectively.

Topical nitroglycerin versus lateral internal sphincterotomy for chronic anal fissure: prospective, randomized trial

Topical nitroglycerin (GTN) is one of the medical treatments of choice in chronic anal fissure. The present prospective, randomized, clinical trial was conducted to study the symptomatic relief, healing, and changes in the maximum anal resting pressure (MARP) in patients with chronic anal fissure comparing topical GTN and lateral sphincterotomy. Forty consecutive patients with chronic anal fissure were randomized for treatment with either topical GTN or internal sphincterotomy (20 patients in each group). Anal manometry was done before treatment in all patients, and 1 h after application of GTN or sphincterotomy. Patients were followed at 2-weekly intervals for 6 weeks for symptomatic relief and healing. Both GTN and sphincterotomy brought about a highly significant, but comparable drop in the MARP after treatment (P < 0.0001 in both groups). Sphincterotomy relieved pain much earlier compared to GTN (70% vs 40% at 2 weeks, P = 0.0032); but after 4 weeks of treatment, pain relief in both groups was comparable. Healing in the sphincterotomy group was also earlier than with GTN (55% vs 0% at 2 weeks, P < 0.0001; and 85% vs 30% at 4 weeks, P < 0.0001); but after 6 weeks, healing in both groups was comparable. Sphincterotomy had a significant incidence of minor, short-term complications; it also required surgical expertise, theatre time, and day-care beds. Nitroglycerin is safe, with mild and tolerable side-effects of headache and local burning sensation. Topical GTN should be the initial treatment in chronic anal fissure. Lateral sphincterotomy should be reserved for patients with severe disabling pain (because pain relief is much faster), and for patients not responding to at least 4 weeks of GTN therapy.

197 Clinical studies of topical glyceryl trinitrate treatment in chronic tendinopathies

197 Clinical studies of topical glyceryl trinitrate treatment in chronic tendinopathies

Two cases of accidental epinephrine injection into a finger

Two cases of accidental epinephrine injection into a finger

Effects of Topical Nitroglycerine Patches and Ointment on Digital Venous Plasma Nitric Oxide Concentrations and Digital Blood Flow in Healthy Conscious Horses

To measure and compare palmar digital venous plasma nitric oxide (NO) concentrations and digital arterial blood flow after application of topical nitroglycerine (NTG). Experimental study. Healthy adult horses (n=8). Digital blood flow was measured by an ultrasonic Doppler flow probe surgically implanted around the medial palmar digital artery. Blood was collected from a catheter placed in the medial palmar digital vein for quantification of NO. NTG patches, NTG ointment or control patches were placed over the palmar digital vessels at the level of the fetlock. Two horses had an intra-arterial infusion of an NTG solution into the medial palmar digital artery in a pilot study. Digital arterial blood flow did not change significantly with application of the NTG patches, NTG ointment, or control patches. There were no statistically significant or biologically important changes in digital venous NO concentrations across time or between treated and control horses. In the pilot study, digital arterial blood flow and palmar digital venous NO concentrations increased with intra-arterial infusion of NTG. In clinically healthy horses, digital arterial blood flow and digital venous plasma NO concentrations did not change significantly with application of the NTG patches/ointment. These treatments are unlikely to have an effect on the digital vasculature of laminitic horses, however, further investigation is warranted. Although NTG patches have been used as a method of decreasing vasomotor tone and improving digital blood flow in horses with laminitis, this study provides evidence in healthy conscious horses that this treatment is not effective in altering digital blood flow.

Topical Glyceryl Trinitrate Application in the Treatment of Chronic Supraspinatus Tendinopathy

Background Topical glyceryl trinitrate therapy has previously demonstrated short-term pain reduction in patients with supraspinatus tendinopathy. Hypothesis Topical glyceryl trinitrate improves outcome measures in patients with supraspinatus tendinopathy. Study Design Randomized controlled clinical trial; Level of evidence, 1. Methods Fifty-three patients (57 shoulders) were recruited, and the authors completed a prospective, randomized, double-blinded, placebo-controlled clinical trial of continuous topical glyceryl trinitrate treatment (1.25 mg/24-h glyceryl trinitrate). Results The glyceryl trinitrate group had significantly reduced shoulder pain with activity, at night, and at rest at week 24 (P =. 03); reduced internal rotation impingement at week 24 (P =. 02); increased range of motion in abduction and internal rotation at week 24 (P =. 04); and increased force at weeks 12 and 24 with supraspinatus muscle testing (P =. 001), external rotation (P =. 04), internal rotation (P =. 01), adduction (P =. 04), and subscapularis pushoff (P =. 01). Forty-six percent of patients on glyceryl trinitrate patches were asymptomatic with activities of daily living at 6 months compared with 24% of patients with tendon rehabilitation alone (P =. 007, χ2 analysis). Mean effect size for all outcome measures was 0.26. Discussion Topical glyceryl trinitrate treatment significantly improved pain scores, range of motion, internal rotation impingement, muscular force, and patient outcomes in patients with supraspinatus tendinopathy. Topical glyceryl trinitrate should be included as part of nonsurgical management of chronic tendinopathies.

Long-term results of topical glyceryl trinitrate ointment in children with anal fissure

Although topical glyceryl trinitrate ointment (GTN) has become a popular treatment for anal fissure in adults, its use in children is still limited. We aimed to determine the effectiveness and safety of topical GTN in the long-term management of anal fissure in children, which has not yet been reported. Thirty-one children with anal fissure who received topical 0.2% GTN treatment between 1997 and 1998 were evaluated in 2004. Ten patients had one or more relapses after initial treatment with 0.2% GTN, all within 1 year of first onset of anal fissure. No further recurrences were diagnosed during the 4-year follow-up period. Although early recurrence can occur, topical GTN ointment is effective in healing chronic anal fissures in children.

Does topical GTN on the sphincter of Oddi facilitate ERCP? A double-blind randomized control trial

Endoscopic retrograde cholangio pancreatography (ERCP) is a technically challenging procedure. Glyceryl trinitrate (GTN) has been shown to reduce tone in the sphincter of Oddi (SO), cannulation of which is a rate-limiting factor. A double-blind randomized control trial was performed to assess whether topical GTN on the SO would facilitate cholangiography and/or bile duct cannulation. 104 patients requiring ERCP for biliary symptoms were randomized into two groups, 52 controls pretreated with 5 ml 0.9% normal saline (NS) and 52 pretreated with 5 ml GTN (concentration 1 mg/ml). There was no significant between the control group and the GTN group in primary cannulation rate (p = 0.76), time taken to cholangiography (p = 0.58), or time to cannulation (p = 0.43). Topically administered GTN to the SO does not aid in obtaining a cholangiogram or cannulation during an ERCP.