Proctitis from Emergency Medicine / Gastrointestinal

eMedicine Journal > Emergency Medicine > Gastrointestinal Proctitis Synonyms, Key Words, and Related Terms: inflammation of the rectum, proctosigmoiditis, rectal tissue ischemia, rectal pain, rectal bleeding, proctitis, mucosal cell loss, acute inflammation of the lamina propria, eosinophilic crypt abscess, endothelial edema of the arterioles, mucosal friability, ulcers, strictures, fistula formation
Author Information \| Introduction \| Clinical \| Differentials \| Workup \| Treatment \| Medication \| Follow-up \| Test Questions \| Bibliography

AUTHOR INFORMATION Section 1 of 10

Authored by Lisandro Irizarry, MD, MPH, FAAEM, Chair and Program Director, Department of Emergency Medicine, Brooklyn Hospital Center; Assistant Professor, Department of Emergency Medicine, Weill Cornell School of Medicine

Lisandro Irizarry, MD, MPH, FAAEM, is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American College of Medical Toxicology, and Society for Academic Emergency Medicine

Edited by Michael S Beeson, MD, MBA, FACEP, Professor of Emergency Medicine, Northeastern Ohio Universities College of Medicine; Program Director, Emergency Medicine Residency, Summa Health System; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Eugene Hardin, MD, FACEP, FAAEM, Chair and Associate Professor, Department of Emergency Medicine, Charles R Drew University of Medicine and Science; Chair, Department of Emergency Medicine, Martin Luther King, Jr/Drew Medical Center; John Halamka, MD, Chief Information Officer, CareGroup Healthcare System, Assistant Professor of Medicine, Department of Emergency Medicine, Beth Israel Deaconess Medical Center; Assistant Professor of Medicine, Harvard Medical School; and Robert E O'Connor, MD, MPH, Director of Education and Research, Department of Emergency Medicine, Christiana Care Health System; Professor of Emergency Medicine, Thomas Jefferson University

Author's Email: Lisandro Irizarry, MD, MPH, FAAEM
Editor's Email: Michael S Beeson, MD, MBA, FACEP

Author's Email:	Lisandro Irizarry, MD, MPH, FAAEM
Editor's Email:	Michael S Beeson, MD, MBA, FACEP

eMedicine Journal, March 7 2006, VOLUME 7, Number 3

INTRODUCTION Section 2 of 10

Background: Proctitis involves an inflammatory change of the rectum (within 15 cm of the dentate line). Proctitis is similar to proctosigmoiditis but is not necessarily associated with proximal extension of disease into the colon and usually does not evolve into ulcerative colitis. If proximal extension does occur, it usually does so within the first 2 years of initial diagnosis.

Pathophysiology: Proctitis involves mucosal cell loss, acute inflammation of the lamina propria, eosinophilic crypt abscess, and endothelial edema of the arterioles. These may improve or progress with subsequent fibrosis of connective tissue and endarteritis of the arterioles, resulting in rectal tissue ischemia and leading to mucosal friability, bleeding, ulcers, strictures, and fistula formation.

Frequency:

In the US: Frequencies of proctitis are associated with their individual etiologies. With radiation therapy, 5-20% of patients display proctitis, usually within 3-24 months after completion of therapy with a total dose greater than 50 Gy.

Race: Incidence is higher in Jewish persons.

Sex: Males are affected more often than females.

Age: Proctitis occurs predominantly in adults.
CLINICAL Section 3 of 10

History:

Idiopathic proctitis

Passage of blood and mucus per rectum

Tenesmus

Occasionally, passage of loose stool, with or without lower abdominal pain or rectal cramping

Infectious proctitis

Pruritus

Rectal and anal pain (may become severe)

Avoidance of defecation
Most common causes: Neisseria gonorrhoeae, Chlamydia trachomatis, herpes simplex virus (HSV) 1 and 2

Indolent and extensive HSV 1 and 2 infections

Tenesmus

Rectal pain

Discharge

Hematochezia

The disease may run its natural course of exacerbations and remissions but is usually more prolonged and severe in patients with immunodeficiency disorders.

Presentations may resemble dermatitis or decubitus ulcers in debilitated, bedridden patients.

A secondary bacterial infection may be present.

Radiation-induced proctitis

Early symptoms include tenesmus and diarrhea that resolve shortly after the treatment period.

Later symptoms of proctitis (occurring months to years after the completion of radiation therapy) include tenesmus, bleeding, low-volume diarrhea, and rectal pain.

Symptoms of radiation-induced proctitis are associated with low-grade obstruction or fistulous tracts into adjacent organs.

Physical:

Mucosal erythema

Mucosal friability

Groups of vesicles eroding into circular superficial ulcers enlarged

Tender inguinal lymph nodes (HSV)

Painless chancres

Hemoccult positive stools

Causes:

N gonorrhoeae

C trachomatis

HSV 1 (10%) and 2 (90%)

Radiation therapy

Immunodeficiency disorders

Crohn disease

Syphilis (usually secondary)

Papillomavirus

Amebiasis

Lymphogranuloma venereum

Ischemia

Toxins (eg, hydrogen peroxide enemas)

Vasculitis

DIFFERENTIALS

Section 4 of 10

Anal Fistulas and Fissures
Chancroid
Diverticular Disease
Foreign Bodies, Rectum
Gonorrhea
HIV Infection and AIDS
Herpes Simplex
Inflammatory Bowel Disease
Syphilis
Vulvovaginitis

Other Problems to be Considered:

Traumatic proctitis
Infections (eg, shigellosis, amebiasis)

WORKUP Section 5 of 10

Lab Studies:

A complete blood count (CBC) is performed to evaluate for chronic or severe blood loss.

A sequential multiple analysis of 7 serum tests (SMA 7) is performed to evaluate for severe electrolyte/fluid losses or to look for evidence of renal insufficiency prior to initiation of medical therapy.

C-reactive protein is elevated in patients with extensive pancolitis but is always normal in patients with distal disease only.

Cultures of rectal swabs help diagnose gonorrhea or chlamydia.

Cultures of vesicular fluid or cytologic scrapings help in the diagnosis of HSV.

Serum venereal disease research laboratory (VDRL) test and dark field examination of scrapings from the base of the chancre reveals spirochetes and confirms the diagnosis of syphilis.

Procedures:

Proctosigmoidoscopy reveals the following:

Pallor or erythema

Loss of usual vascularity of mucosa

Prominent telangiectasia

Friability

Bleeding

Ulcerations

Edema

Scattered areas of scarring

Vesicles/pustules

Strictures

Biopsy for histology, culture, viral studies, and Chlamydia studies

Colonoscopy to exclude more proximal involvement

TREATMENT

Section 6 of 10

Emergency Department Care:

After life-threatening conditions have been excluded or controlled, aim for providing patient comfort during the examination.

Treatment depends upon the etiology.

Sitz baths (may provide relief)

Steroid enemas or suppositories for ulcerative proctitis

Ceftriaxone and doxycycline for gonorrheal proctitis

Acyclovir for herpetic proctitis

Tetracycline or doxycycline for chlamydial proctitis

Consultations:

Consult colorectal surgery or gastroenterology for further evaluation of the lower gastrointestinal (GI) tract by sigmoidoscopy, if indicated (to rule out more proximal disease), after anoscopy.

A colorectal surgical consultation also may be considered for management/evaluation of deep tissue infection that is not amenable to incision and drainage in the ED.

MEDICATION

Section 7 of 10

Drug therapy consists of antibiotics, antivirals, and GI agents.

Drug Category: Antibiotics -- Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Drug Name
Ceftriaxone (Rocephin) -- Used because of an increasing prevalence of penicillinase producing N gonorrhoeae. It inhibits bacterial cell wall synthesis by binding to one or more of the penicillin binding proteins, causing bacterial growth inhibition.
Adult Dose 250 mg IM once
Pediatric Dose Neonates > 7 days: 25-50 mg/kg IM once; not to exceed 125 mg
Infant or child: 125 mg IM once plus doxycycline
Contraindications Documented hypersensitivity
Interactions Aminoglycosides increase nephrotoxic potential; probenecid increases effects by decreasing clearance
Pregnancy D - Unsafe in pregnancy
Precautions Caution in renal impairment
Drug Name
Doxycycline (Doryx, Bio-Tab, Vibramycin) -- Required with ceftriaxone for the treatment of gonorrheal proctitis. Inhibits protein synthesis and, thus, bacterial growth by binding with the 30S and possibly the 50S ribosomal subunits of susceptible bacteria.
Adult Dose Acute infections: 200 mg PO immediately, then 100 mg PO hs on d 1, followed by 100 mg PO bid for 3 d; or 300 mg PO stat followed by 300 mg PO in 1 h; alternatively, use 100 mg PO bid for 7 d
Pediatric Dose <8 years: Not recommended
>8 years: 2-5 mg/kg/d PO qd or divided bid; not to exceed 200 mg/d
Contraindications Documented hypersensitivity; severe hepatic dysfunction
Interactions Antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate can decrease bioavailability
Pregnancy D - Unsafe in pregnancy
Precautions Avoid prolonged exposure to sunlight or tanning equipment to prevent a photosensitivity reaction; use of tetracyclines during tooth development (last half of pregnancy through age 8 y) can cause permanent discoloration of teeth
Drug Name
Benzathine penicillin (Bicillin L-A) -- A bactericidal used in the treatment of rectal syphilis. It interferes with bacterial cell wall synthesis during active multiplication, inhibiting bacterial growth.
Adult Dose 2.4 million U IM once in 2 injection sites
Pediatric Dose 50,000 U/kg IM once; not to exceed 2.4 million U
Contraindications Documented hypersensitivity
Interactions Probenecid can increase the effects by decreasing clearance; conversely, coadministration of tetracyclines can decrease effects
Pregnancy B - Usually safe but benefits must outweigh the risks.
Precautions Caution in impaired renal function
Drug Name
Tetracycline (Sumycin) -- Treats susceptible bacterial infections of both gram-positive and gram-negative organisms as well as infections caused by Mycoplasma, Chlamydia, and Rickettsia species. Inhibits bacterial protein synthesis and, thus, bacterial growth by binding with 30S and possibly 50S ribosomal subunit(s) of susceptible bacteria.
Adult Dose 250-500 mg PO q6h
Pediatric Dose 25-50 mg/kg/d PO divided q6h
Contraindications Documented hypersensitivity; severe hepatic dysfunction
Interactions Antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate can decrease bioavailability; can increase hypoprothrombinemic effects of anticoagulants; coadministration can decrease the pharmacologic effects of oral contraceptives, causing breakthrough bleeding and an increased risk of pregnancy
Pregnancy D - Unsafe in pregnancy
Precautions Prolonged exposure to sunlight or tanning equipment can cause a photosensitivity reaction; use lower-than-usual doses in patients with renal impairment; use of tetracyclines during tooth development (last half of pregnancy through age 8 y) can cause a permanent discoloration of teeth; never administer outdated tetracyclines, the degradation products are highly nephrotoxic and can cause a Fanconilike syndrome
Drug Category: Rectal anti-inflammatory agents -- These agents decrease inflammation associated with proctitis, perhaps by inhibiting prostaglandin synthesis.
Drug Name
Sulfasalazine (Azulfidine) -- Useful in the management of ulcerative colitis; acts locally in the colon to decrease the inflammatory response and systemically inhibits prostaglandin synthesis.
Adult Dose Initial dose: 1 g PO tid/qid
Maintenance dose: 2 g/d PO divided tid/qid
Pediatric Dose <2 years: Not established
>2 years: 40-60 mg/kg/d PO in 3-6 divided doses
Maintenance dose: 20-30 mg/kg/d PO divided qid
Contraindications Documented hypersensitivity; GI or GU obstruction
Interactions Decreases the effect of iron, digoxin, and folic acid; conversely, increases effect of oral anticoagulants, oral hypoglycemic agents, and methotrexate
Pregnancy B - Usually safe but benefits must outweigh the risks.
Precautions Renal or hepatic impairment; blood dyscrasias; urinary obstruction
Drug Name
Mesalamine (Rowasa, Asacol, Canasa, Pentasa) -- Used for treatment of mildly to moderately active ulcerative colitis. The usual course of therapy in adults is 3-6 wk. Some patients may need concurrent oral and rectal therapy.
Adult Dose Oral: 1 g cap PO qid or 800 mg tab PO tid
Rectal: One 500-mg supp PR bid or one 4-g susp enema PR qd (retained for 8 h)
Pediatric Dose Not established
Contraindications Documented hypersensitivity to mesalamine or to suppository vehicle (saturated vegetable fatty acid esters)
Interactions Decreases effects of iron, digoxin, and folic acid; conversely, it increases the effect of oral anticoagulants, methotrexate, and oral hypoglycemic agents
Pregnancy B - Usually safe but benefits must outweigh the risks.
Precautions Elderly persons may have difficulty administering and retaining rectal suppositories; use caution in patients with renal or hepatic impairment; suspension contains potassium metabisulfite, so care must be taken in individuals with documented sulfite allergy
Drug Category: Antivirals -- These agents are used for the treatment of herpes-related proctitis. They inhibit viral replication by competing with deoxyguanosine triphosphate for viral DNA polymerase.
Drug Name
Acyclovir (Zovirax) -- Reduces duration of symptomatic lesions. Indicated for patients presenting within 48 h of experiencing rash. Patients taking acyclovir experience less pain and faster resolution of cutaneous lesions.
Adult Dose Initial episode: 200 mg PO q4h (while awake) 5 times/d for 10 d
Recurrence: 200 mg PO q4h (while awake) 5 times/d for 10 d
Pediatric Dose Not established
Suggested dose: 10-20 mg/kg/dose PO (up to 800 mg) qid for 5 d; start treatments within 24 h of rash onset
Contraindications Documented hypersensitivity
Interactions Concomitant use of probenecid or zidovudine prolongs half-life and thus increases CNS toxicity
Pregnancy B - Usually safe but benefits must outweigh the risks.
Precautions Renal failure; coadministration of other nephrotoxic drugs
FOLLOW-UP Section 8 of 10

Drug Name	Ceftriaxone (Rocephin) -- Used because of an increasing prevalence of penicillinase producing N gonorrhoeae. It inhibits bacterial cell wall synthesis by binding to one or more of the penicillin binding proteins, causing bacterial growth inhibition.
Adult Dose	250 mg IM once
Pediatric Dose	Neonates > 7 days: 25-50 mg/kg IM once; not to exceed 125 mg Infant or child: 125 mg IM once plus doxycycline
Contraindications	Documented hypersensitivity
Interactions	Aminoglycosides increase nephrotoxic potential; probenecid increases effects by decreasing clearance
Pregnancy	D - Unsafe in pregnancy
Precautions	Caution in renal impairment

Drug Name	Doxycycline (Doryx, Bio-Tab, Vibramycin) -- Required with ceftriaxone for the treatment of gonorrheal proctitis. Inhibits protein synthesis and, thus, bacterial growth by binding with the 30S and possibly the 50S ribosomal subunits of susceptible bacteria.
Adult Dose	Acute infections: 200 mg PO immediately, then 100 mg PO hs on d 1, followed by 100 mg PO bid for 3 d; or 300 mg PO stat followed by 300 mg PO in 1 h; alternatively, use 100 mg PO bid for 7 d
Pediatric Dose	<8 years: Not recommended >8 years: 2-5 mg/kg/d PO qd or divided bid; not to exceed 200 mg/d
Contraindications	Documented hypersensitivity; severe hepatic dysfunction
Interactions	Antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate can decrease bioavailability
Pregnancy	D - Unsafe in pregnancy
Precautions	Avoid prolonged exposure to sunlight or tanning equipment to prevent a photosensitivity reaction; use of tetracyclines during tooth development (last half of pregnancy through age 8 y) can cause permanent discoloration of teeth

Drug Name	Benzathine penicillin (Bicillin L-A) -- A bactericidal used in the treatment of rectal syphilis. It interferes with bacterial cell wall synthesis during active multiplication, inhibiting bacterial growth.
Adult Dose	2.4 million U IM once in 2 injection sites
Pediatric Dose	50,000 U/kg IM once; not to exceed 2.4 million U
Contraindications	Documented hypersensitivity
Interactions	Probenecid can increase the effects by decreasing clearance; conversely, coadministration of tetracyclines can decrease effects
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Caution in impaired renal function

Drug Name	Tetracycline (Sumycin) -- Treats susceptible bacterial infections of both gram-positive and gram-negative organisms as well as infections caused by Mycoplasma, Chlamydia, and Rickettsia species. Inhibits bacterial protein synthesis and, thus, bacterial growth by binding with 30S and possibly 50S ribosomal subunit(s) of susceptible bacteria.
Adult Dose	250-500 mg PO q6h
Pediatric Dose	25-50 mg/kg/d PO divided q6h
Contraindications	Documented hypersensitivity; severe hepatic dysfunction
Interactions	Antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate can decrease bioavailability; can increase hypoprothrombinemic effects of anticoagulants; coadministration can decrease the pharmacologic effects of oral contraceptives, causing breakthrough bleeding and an increased risk of pregnancy
Pregnancy	D - Unsafe in pregnancy
Precautions	Prolonged exposure to sunlight or tanning equipment can cause a photosensitivity reaction; use lower-than-usual doses in patients with renal impairment; use of tetracyclines during tooth development (last half of pregnancy through age 8 y) can cause a permanent discoloration of teeth; never administer outdated tetracyclines, the degradation products are highly nephrotoxic and can cause a Fanconilike syndrome

Drug Name	Sulfasalazine (Azulfidine) -- Useful in the management of ulcerative colitis; acts locally in the colon to decrease the inflammatory response and systemically inhibits prostaglandin synthesis.
Adult Dose	Initial dose: 1 g PO tid/qid Maintenance dose: 2 g/d PO divided tid/qid
Pediatric Dose	<2 years: Not established >2 years: 40-60 mg/kg/d PO in 3-6 divided doses Maintenance dose: 20-30 mg/kg/d PO divided qid
Contraindications	Documented hypersensitivity; GI or GU obstruction
Interactions	Decreases the effect of iron, digoxin, and folic acid; conversely, increases effect of oral anticoagulants, oral hypoglycemic agents, and methotrexate
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Renal or hepatic impairment; blood dyscrasias; urinary obstruction

Drug Name	Mesalamine (Rowasa, Asacol, Canasa, Pentasa) -- Used for treatment of mildly to moderately active ulcerative colitis. The usual course of therapy in adults is 3-6 wk. Some patients may need concurrent oral and rectal therapy.
Adult Dose	Oral: 1 g cap PO qid or 800 mg tab PO tid Rectal: One 500-mg supp PR bid or one 4-g susp enema PR qd (retained for 8 h)
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity to mesalamine or to suppository vehicle (saturated vegetable fatty acid esters)
Interactions	Decreases effects of iron, digoxin, and folic acid; conversely, it increases the effect of oral anticoagulants, methotrexate, and oral hypoglycemic agents
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Elderly persons may have difficulty administering and retaining rectal suppositories; use caution in patients with renal or hepatic impairment; suspension contains potassium metabisulfite, so care must be taken in individuals with documented sulfite allergy

Drug Name	Acyclovir (Zovirax) -- Reduces duration of symptomatic lesions. Indicated for patients presenting within 48 h of experiencing rash. Patients taking acyclovir experience less pain and faster resolution of cutaneous lesions.
Adult Dose	Initial episode: 200 mg PO q4h (while awake) 5 times/d for 10 d Recurrence: 200 mg PO q4h (while awake) 5 times/d for 10 d
Pediatric Dose	Not established Suggested dose: 10-20 mg/kg/dose PO (up to 800 mg) qid for 5 d; start treatments within 24 h of rash onset
Contraindications	Documented hypersensitivity
Interactions	Concomitant use of probenecid or zidovudine prolongs half-life and thus increases CNS toxicity
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Renal failure; coadministration of other nephrotoxic drugs

Further Outpatient Care:

Discharge if no life-threatening condition exists and the patient is able to comply with the therapeutic regimen.

Discharge should include follow-up with a colorectal surgeon or gastroenterologist who will follow the patient's progress clinically and endoscopically, in addition to following results of cultures, labs, and biopsies.

In/Out Patient Meds:

Maintenance medical therapy is not used routinely in idiopathic proctitis unless the patient is slow to respond, difficult to control, or has frequent flare-ups.

In radiation proctitis, no evidence indicates that corticosteroids, and/or the various aminosalicylic acid derivations given as an enema or orally, are beneficial in preventing the progression of the disease.

Complications:

Chronic ulcerative colitis

Fistula formation

Abscess

Treatment failure

Perforation

Prognosis:

Failure rates as high as 35% have been reported following treatment of rectal gonorrhea; symptoms frequently recur.

Most surgeons favor a diverting colostomy for medically intractable proctitis.

Patient Education:

For excellent patient education resources, visit eMedicine's Esophagus, Stomach, and Intestine Center. Also, see eMedicine's patient education articles, Anal Abscess, Rectal Pain, and Rectal Bleeding.

TEST QUESTIONS

Section 9 of 10

CME Question 1: Which of the following statements is not accurate regarding proctitis?

A: Ulcerating proctitis usually is associated with herpes simplex virus (HSV) 1 or HSV 2.
B: Proctitis involves the area within 15 cm of the dentate line.
C: Symptoms of proctitis do not include constipation but are associated with diarrhea.
D: Urinary retention may be seen in proctitis.
E: Prolapse internal hemorrhoids may mimic proctitis.

The correct answer is C: Proctitis may present with either low-volume diarrhea or constipation.

CME Question 2: Which of the following is not included in the workup of proctitis?

A: Ultrasound
B: MRI
C: Proctosigmoidoscopy
D: Erythrocyte sedimentation rate (ESR)
E: Barium enema

The correct answer is D: ESR is not elevated in proctitis; however, C-reactive protein is elevated in extensive pancolitis but is nearly always normal in distal disease.

Pearl Question 1 (T/F): Proctitis occurs in the large intestine.

The correct answer is False: Proctitis occurs in the rectum (within 15 cm of the dentate line).

Pearl Question 2 (T/F): Neisseria gonorrhoeae, Chlamydia trachomatis, and herpes simplex virus 1 & 2 are the most common causes of infectious proctitis.

The correct answer is True: Other infectious causes include syphilis (usually secondary), papillomavirus, amebiasis, and lymphogranuloma venereum.

Pearl Question 3 (T/F): Stomach discomfort and malaise are early symptoms of proctitis associated with radiation therapy.

The correct answer is False: Tenesmus and diarrhea that resolve shortly after the treatment period are early symptoms of proctitis associated with radiation therapy.

Pearl Question 4 (T/F): Fifty percent of herpes virus infections associated with infectious proctitis are herpes simplex 2.

The correct answer is False: Ninety percent of herpes virus infections associated with infectious proctitis are herpes simplex 2.
BIBLIOGRAPHY Section 10 of 10

Babb RR: Radiation proctitis: a review. Am J Gastroenterol 1996 Jul; 91(7): 1309-11[Medline].
Bassford T: Treatment of common anorectal disorders. Am Fam Physician 1992 Apr; 45(4): 1787-94[Medline].
Bitton A: Medical Management of Ulcerative Proctitis, Proctosigmoiditis, and left-sided colitis. Semin Gastrointest Dis 2001; 12(4): 263-274[Medline].
Denton AS, Andreyev HJ, Forbes A, Maher EJ: Systematic review for non-surgical interventions for the management of late radiation proctitis. Br J Cancer 2002 Jul 15; 87(2): 134-43[Medline].
Rafal RB, Nichols JN, Cennerazzo WJ, et al: MRI for evaluation of perianal inflammation. Abdom Imaging 1995 May-Jun; 20(3): 248-52[Medline].
Regueiro MD: Diagnosis and treatment of ulcerative proctitis. J Clin Gastroenterol 2004 Oct; 38(9): 733-40[Medline].
Spencer CM, McTavish D: Budesonide. A review of its pharmacological properties and therapeutic efficacy in inflammatory bowel disease. Drugs 1995 Nov; 50(5): 854-72[Medline].

NOTE:
Medicine is a constantly changing science and not all therapies are clearly established. New research changes drug and treatment therapies daily. The authors, editors, and publisher of this journal have used their best efforts to provide information that is up-to-date and accurate and is generally accepted within medical standards at the time of publication. However, as medical science is constantly changing and human error is always possible, the authors, editors, and publisher or any other party involved with the publication of this article do not warrant the information in this article is accurate or complete, nor are they responsible for omissions or errors in the article or for the results of using this information. The reader should confirm the information in this article from other sources prior to use. In particular, all drug doses, indications, and contraindications should be confirmed in the package insert. FULL DISCLAIMER

NOTE:

Medicine is a constantly changing science and not all therapies are clearly established. New research changes drug and treatment therapies daily. The authors, editors, and publisher of this journal have used their best efforts to provide information that is up-to-date and accurate and is generally accepted within medical standards at the time of publication. However, as medical science is constantly changing and human error is always possible, the authors, editors, and publisher or any other party involved with the publication of this article do not warrant the information in this article is accurate or complete, nor are they responsible for omissions or errors in the article or for the results of using this information. The reader should confirm the information in this article from other sources prior to use. In particular, all drug doses, indications, and contraindications should be confirmed in the package insert. FULL DISCLAIMER