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Ability of naloxone to enhance the colonoscopic appearance of normal colon vasculature and colon vascular ectasias
Ability of naloxone to enhance the colonoscopic appearance of normal colon vasculature and colon vascular ectasias Lawrence J. Brandt, MD, Mitchell K. Spinnell, MD Bronx, New York
Background: Colon vascular ectasias are a common cause of lower intestinal bleeding among the elderly. The lesions may be difficult to diagnose at colonoscopy because they are small and their appearance may be influenced by the patient’s blood pressure, blood volume, and narcotic sedation during the procedure. The purpose of this study was to determine whether naloxone influenced the appearance of colon vascular ectasias at colonoscopy. Methods: One hundred forty-four patients older than 60 years undergoing complete colonoscopy participated in the study. Medications were given in the usual doses. After a 2-minute inspection of the cecum and ascending colon, naloxone was given, followed by another 2-minute observation period. Photographic documentation of areas of interest was obtained before and after administration of naloxone. Results: One hundred fourteen patients (79%) had no ectasias before or after administration of naloxone. Fourteen (9.7%) initially had normal vessels, and the vessels became more prominent; 4 (2.7%) initially had no ectasias, but ectasias later developed. Four patients (2.7%) had ectasias before administration of naloxone that did not change; 8 (5.4%) had ectasias before administration of naloxone that increased in size (3 patients), number (7 patients), or both (2 patients). Conclusions: Naloxone can enhance the appearance of normal colonic vasculature and ectasias. Naloxone is an important adjunctive medication for patients undergoing examinations for lower intestinal bleeding. (Gastrointest Endosc 1999;49:79-83.) Colon vascular ectasias (CVEs) are an important source of lower intestinal bleeding among elderly persons.1 CVEs occur most often in the cecum and ascending colon. The cause of CVEs is unknown, but the lesions are believed to represent a degenerative process associated with aging.2 Therefore, they are more common among elderly as opposed to younger persons. CVEs can be symptomatic or asymptomatic, and their natural history is not completely understood. Received September 10, 1997. For revision January 14, 1998. Accepted June 16, 1998. From the Division of Gastroenterology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York. Reprint requests: Lawrence J. Brandt, MD, Division of Gastroenterology, Montefiore Medical Center, 111 East 210th St., Bronx, NY 10467. Copyright © 1999 by the American Society for Gastrointestinal Endoscopy 0016-5107/99/$8.00 + 0 37/1/92454 VOLUME 49, NO. 1, 1999
The diagnosis of CVEs may be difficult. Even more challenging is linking the presence of CVEs to hemorrhage in the absence of overt bleeding. In studies involving patients with positive results of fecal occult blood tests, anemia, or hemorrhage, investigators have detected CVEs among 2.6% to 6.2% of patients.3 The sensitivity of colonoscopy in the detection of these lesions is unknown, but it probably approaches 80% to 90%.4 Even when present, however, CVEs may be difficult to find at colonoscopy. In part this is because of their small size and because their appearance may be influenced by the patient’s blood pressure, degree of anemia, and effective blood volume and the routine use of narcotic analgesics such as meperidine during colonoscopy.5 It has been suggested that the vasodilating effect of narcotic sedation causes a transient decrease in mucosal blood flow, which obscures the distinct red appearance of CVEs.6 This concern and an abstract of a study that showed naloxone GASTROINTESTINAL ENDOSCOPY
79
L Brandt, M Spinnell
A
Naloxone enhancement of colonoscopic appearance of colon vasculature
A
B B
Figure 1. A, Colon vascular ectasia with pale, blotchy appearance. B, Increase in vascular prominence after naloxone administration.
enhanced the appearance of CVEs7 prompted our study to determine whether the narcotic antagonistic effects of naloxone can be used to enhance the appearance of CVEs at colonoscopy among patients who receive meperidine for sedation. PATIENTS AND METHODS All patients older than 60 years were eligible for the study if they underwent colonoscopy at Montefiore Medical Center during the period January through December 1996. A complete examination to the cecum was performed. The indication for colonoscopy had no bearing on patient selection. One hundred forty-four patients met the inclusion criteria. Colonoscopy was performed with a standard video colonoscope by an experienced investigator, usually in conjunction with a gastroenterology resident. The patient’s pulse, blood pressure, and oxygen saturation were monitored routinely during all procedures. Medications (12.5 to 75 mg meperidine and 0.5 to 3 mg midazolam) were given in the usual doses to achieve adequate sedation as determined by the examining physician. 80
GASTROINTESTINAL ENDOSCOPY
Figure 2. A, Subtle appearance of colon vascular ectasia. B, Deepening intensity of vessels after naloxone administration.
After a 2-minute inspection of the cecum and ascending colon, 0.4 to 0.8 mg naloxone hydrochloride were given intravenously, and drug administration was followed by another observation period. The standard dose range of naloxone was chosen for its ability to reverse the cardiopulmonary and psychomotor effects of an opiate agonist such as meperidine. In our endoscopic unit, naloxone customarily is used by all practitioners to counteract the cardiorespiratory depressant effects of meperidine. It is standard practice to give the drug either on withdrawal of the instrument or at the conclusion of the procedure, although any compromise in narcotic-induced cardiorespiratory function would prompt immediate use. Individual practitioners chose the administered dose according to their general preference. Areas of interest were photodocumented in all instances before and after administration of naloxone whether or not vascular lesions were observed. Photographs were analyzed by a reviewer for anatomic consistency, vessel appearance, morphologic similarity, size, and number and location of lesions. The reviewer, who did not participate in the procedures, was blinded to which photographs were taken before and after naloxone administration. A vasoactive response to naloxone was defined as a normal vessel VOLUME 49, NO. 1, 1999
Naloxone enhancement of colonoscopic appearance of colon vasculature
L Brandt, M Spinnell
Table 1. Indications for colonoscopy and vascular appearance before naloxone administration Total Indication Vascular Overt bleeding Occult bleeding Anemia CVEs Subtotal Nonvascular Polyps Inflammatory bowel disease Unknown Diarrhea Colon cancer Altered bowel habits Constipation Screening Subtotal Total
No CVEs
CVEs
No.
%
No.
%
No.
%
29 22 8 1 60
20 15 6 1 42
24 21 8 1 54
17 15 6 1 38
5 1 0 0 6
4 1 — — 4
31 7 27 4 7 3 3 2 84 144
22 5 19 4 5 2 2 1 58 100
26 7 23 4 7 3 3 2 75 129
18 5 16 3 5 2 2 1 52 90
5 0 4 0 0 0 0 0 9 15
4 — 3 — — — — — 6 10
or CVE that became more prominent or a CVE that appeared after naloxone administration.
one. None of the ectasias was found to bleed spontaneously after administration of naloxone.
RESULTS
DISCUSSION
One hundred forty-four patients met the inclusion criteria and were enrolled for evaluation. Indications for colonoscopy varied among subjects (Table 1). One hundred fourteen subjects (79%) had no CVEs before or after administration of naloxone. Twelve patients (8.3%) had CVEs detected at initial inspection. After naloxone administration, an additional 4 patients who were not previously found to have abnormal colonic vessels had evidence of CVEs, bringing the incidence of CVEs in the study population to 11.1%. Among these patients, 1 to 3 CVEs appeared after administration of naloxone. Six patients (4%) found to have CVEs were being examined because of overt bleeding, occult bleeding, anemia, or known CVEs. Nine patients (6%) found to have CVEs had nonvascular indications for colonoscopy (Table 1). Fourteen patients had normal colonic vessels that became more prominent after administration of naloxone. Eight patients (5.4%) had CVEs before administration of naloxone that changed after the drug was administered (Figs. 1 through 3). In 3 patients the size or intensity of the CVEs increased, in 7 the number of CVEs increased, and in 2 patients CVEs increased in size and number. Four patients with clearly visible CVEs at the initial survey had neither a change in the intensity of the vascular pattern nor an increase in number of abnormal vessels after administration of naloxone. Twenty-two patients (15.3%) had a vasoactive response to nalox-
CVEs are affected by narcotic sedation. Meperidine, a µ opiate agonist, is used commonly for sedation before colonoscopy. Meperidine has hemodynamic effects, including myocardial depression, hypotension, and decreased peripheral vascular resistance. It also activates intestinal mast cells to release histamine.8 Through these mechanisms, meperidine and similar analgesics may cause a transient decrease in mucosal blood flow that in some persons may diminish the intensity of the normal colonic vasculature or obscure the appearance of CVEs. Naloxone, an opiate antagonist, given in standard intravenous or intramuscular doses of 0.4 to 0.8 mg can prevent or reverse the effects of opiate agonists such as meperidine. Respiratory depression, hypotension, and psychomotor retardation can be reversed within 1 to 2 minutes of administration because the drug has a rapid onset of action. The duration of the antagonist effect is variable; it usually lasts 1 to 4 hours. Then the drug undergoes conjugation in the liver and is rendered inactive. Although vasodilation, or at least reversal of colonic hypoperfusion, is believed to be involved in naloxone enhancement of CVEs, it is of interest that carbon dioxide, also a vasodilator, when administered as the insufflation gas during colonoscopy, increases colon blood flow9 but does not enhance the appearance of colon vascular ectasias (L.J. Brandt, unpublished observation). Intra-arterial vasodilators such as
VOLUME 49, NO. 1, 1999
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81
A
E
B
F
C
G
D
H
Figure 3. A–H, Progressive changes in the appearance of colon vascular ectasia after administration of naloxone. The appearance of the CVE changes from a subtle, pale, pinkish blotch to a fan-shaped lesion and then evolves into a congested network of vessels. 82
GASTROINTESTINAL ENDOSCOPY
VOLUME 49, NO. 1, 1999
Naloxone enhancement of colonoscopic appearance of colon vasculature
papaverine and intravenously administered mesenteric vasodilators, including urotensin I, sauvagine, and other corticotropin-releasing factor–like peptides have been used clinically and experimentally to increase mesenteric blood flow,10,11 but their effects, if any, on CVEs have not been studied. Data from our study demonstrated that for some elderly patients undergoing colonoscopy for bleeding or a variety of other indications, administration of naloxone after narcotic sedation may increase mucosal blood flow and enhance the gross appearance of the colonic vasculature. Although photodocumentation was obtained in most instances, areas of normal mucosa in which changes (i.e., CVEs) appeared after naloxone administration were not necessarily photographed beforehand. This raises the possibility of overestimating the effect of naloxone by reporting a positive response when potentially the CVE was missed at initial inspection. Routine videography would obviate some of this bias. Nevertheless photographs clearly documented a vascular enhancing effect of naloxone. The study also could have been strengthened with an analysis of the vascular response to naloxone in the absence of prior narcotic sedation. Naloxone alone could have an effect on microvascular tissue perfusion by antagonizing endogenous opioid receptors in colonic vessels, although this has not been demonstrated in humans. Opioid receptors have been found in the colon, and various studies have shown the effect of naloxone receptor antagonism on endogenous opioids in animal models such as the rat dorsal horn ganglia.12 Naloxone might enhance the colonic vasculature and CVEs by reversing the vasoactive effect of narcotics and their action on arterial blood pressure. Although blood pressure was monitored during the entire procedure and no significant hypotensive episodes were encountered, blood pressure measurements before and after administration of naloxone were not specifically compared. Whether or not naloxone has a direct effect on the colonic microvasculature or acts by means of narcotic reversal to increase arterial blood pressure, its practical effect is to increase the diagnostic yield of colonoscopy for CVEs previously not found. Twenty-two patients (15.3%) had a vascular response to naloxone. Although a vascular change was found most often in normal blood vessels (14 patients, 9.7%), the effect on CVEs has more clinical relevance. After administration of naloxone, CVEs may become more apparent (Figs. 1 through 3). As a result, CVEs might be less likely to be overlooked, particularly in the setting of anemia or low circulating blood volume, a common scenario, particularly
VOLUME 49, NO. 1, 1999
L Brandt, M Spinnell
after serious lower intestinal hemorrhage. More impressive is the observation that naloxone caused previously unseen CVEs to “bloom.” As such, naloxone may play an important role as an adjunctive medication for elderly patients undergoing examinations for (cryptogenic) lower intestinal bleeding. Moreover, use of naloxone might be helpful in endoscopic treatment by enabling identification of lesions that otherwise might not be seen and might thus remain untreated. Additional studies are needed to verify, quantify, and further describe the utility of narcotic reversal with naloxone. In some centers, drugs that relax smooth muscle (e.g., glucagon and anticholinergics) are used to facilitate passage of a colonoscope though areas of luminal narrowing. It is conceivable that such agents might enhance the appearance of the colonic vasculature and CVEs. In summary, naloxone can enhance normal colonic vasculature, increase the vascularity of CVEs, and cause previously unseen CVEs to “bloom.” Hence naloxone may have a useful role when the cecum and ascending colon are being inspected for CVEs, especially among patients undergoing examinations for bleeding lesions in the lower intestine. REFERENCES 1. Tedesco FJ, Griffin JW Jr, Khan AQ. Vascular ectasia of the colon: clinical, colonoscopic and radiographic features. J Clin Gastroenterol 1980;2:233-8. 2. Boley S, Dibiase A, Brandt L, et al. Lower intestinal bleeding in the elderly. Am J Surg 1979;137:57-64. 3. Richter JM, Christensen MR, Colditz GA, et al. Angiodysplasia: natural history and efficacy of therapeutic interventions. Dig Dis Sci 1989;34:1542-6. 4. Richter JM, Hedberg SE, Athanasoulis CA, et al. Angiodysplasia: clinical presentation and colonoscopic diagnosis. Dig Dis Sci 1984;29:481-5. 5. Foutch PG. Angiodysplasia of the gastrointestinal tract. Am J Gastroenterol 1993;88:807-18. 6. Boley SJ, Brandt LJ. Vascular ectasias of the colon, 1986. Dig Dis Sci 1986;31:26S-42S. 7. Deal SE, Zfass AM, Duckworth PF, McHenry L. Arteriovenous malformations (AVMs): are they concealed by meperidine [abstract]? Am J Gastroenterol 1991;86:1352. 8. Huang YF, Upton RN, Rutten AJ, et al. The hemodynamic effects of intravenous bolus doses of meperidine in conscious sheep. Anesth Analg 1994;78:442-9. 9. Brandt LJ, Boley SJ, Sammartano R. Carbon dioxide and room air insufflation of the colon. Gastrointest Endosc 1986;32:324-9. 10. MacCannell KL, Comparison of an intravenous selective mesenteric vasodilator with intraarterial papaverine in experimental nonocclusive mesenteric ischemia. Gastroenterology 1986;91:79-83. 11. Boley SJ, Brandt LJ. Selective mesenteric vasodilators. Gastroenterology 1986;91:247-9. 12. Levine JD, Fields HL, Basbaum AI. Peptides and the primary afferent nociceptor. J Neurosci 1993;13:2273-86.
GASTROINTESTINAL ENDOSCOPY
83
Background: Colon vascular ectasias are a common cause of lower intestinal bleeding among the elderly. The lesions may be difficult to diagnose at colonoscopy because they are small and their appearance may be influenced by the patient’s blood pressure, blood volume, and narcotic sedation during the procedure. The purpose of this study was to determine whether naloxone influenced the appearance of colon vascular ectasias at colonoscopy. Methods: One hundred forty-four patients older than 60 years undergoing complete colonoscopy participated in the study. Medications were given in the usual doses. After a 2-minute inspection of the cecum and ascending colon, naloxone was given, followed by another 2-minute observation period. Photographic documentation of areas of interest was obtained before and after administration of naloxone. Results: One hundred fourteen patients (79%) had no ectasias before or after administration of naloxone. Fourteen (9.7%) initially had normal vessels, and the vessels became more prominent; 4 (2.7%) initially had no ectasias, but ectasias later developed. Four patients (2.7%) had ectasias before administration of naloxone that did not change; 8 (5.4%) had ectasias before administration of naloxone that increased in size (3 patients), number (7 patients), or both (2 patients). Conclusions: Naloxone can enhance the appearance of normal colonic vasculature and ectasias. Naloxone is an important adjunctive medication for patients undergoing examinations for lower intestinal bleeding. (Gastrointest Endosc 1999;49:79-83.) Colon vascular ectasias (CVEs) are an important source of lower intestinal bleeding among elderly persons.1 CVEs occur most often in the cecum and ascending colon. The cause of CVEs is unknown, but the lesions are believed to represent a degenerative process associated with aging.2 Therefore, they are more common among elderly as opposed to younger persons. CVEs can be symptomatic or asymptomatic, and their natural history is not completely understood. Received September 10, 1997. For revision January 14, 1998. Accepted June 16, 1998. From the Division of Gastroenterology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York. Reprint requests: Lawrence J. Brandt, MD, Division of Gastroenterology, Montefiore Medical Center, 111 East 210th St., Bronx, NY 10467. Copyright © 1999 by the American Society for Gastrointestinal Endoscopy 0016-5107/99/$8.00 + 0 37/1/92454 VOLUME 49, NO. 1, 1999
The diagnosis of CVEs may be difficult. Even more challenging is linking the presence of CVEs to hemorrhage in the absence of overt bleeding. In studies involving patients with positive results of fecal occult blood tests, anemia, or hemorrhage, investigators have detected CVEs among 2.6% to 6.2% of patients.3 The sensitivity of colonoscopy in the detection of these lesions is unknown, but it probably approaches 80% to 90%.4 Even when present, however, CVEs may be difficult to find at colonoscopy. In part this is because of their small size and because their appearance may be influenced by the patient’s blood pressure, degree of anemia, and effective blood volume and the routine use of narcotic analgesics such as meperidine during colonoscopy.5 It has been suggested that the vasodilating effect of narcotic sedation causes a transient decrease in mucosal blood flow, which obscures the distinct red appearance of CVEs.6 This concern and an abstract of a study that showed naloxone GASTROINTESTINAL ENDOSCOPY
79
L Brandt, M Spinnell
A
Naloxone enhancement of colonoscopic appearance of colon vasculature
A
B B
Figure 1. A, Colon vascular ectasia with pale, blotchy appearance. B, Increase in vascular prominence after naloxone administration.
enhanced the appearance of CVEs7 prompted our study to determine whether the narcotic antagonistic effects of naloxone can be used to enhance the appearance of CVEs at colonoscopy among patients who receive meperidine for sedation. PATIENTS AND METHODS All patients older than 60 years were eligible for the study if they underwent colonoscopy at Montefiore Medical Center during the period January through December 1996. A complete examination to the cecum was performed. The indication for colonoscopy had no bearing on patient selection. One hundred forty-four patients met the inclusion criteria. Colonoscopy was performed with a standard video colonoscope by an experienced investigator, usually in conjunction with a gastroenterology resident. The patient’s pulse, blood pressure, and oxygen saturation were monitored routinely during all procedures. Medications (12.5 to 75 mg meperidine and 0.5 to 3 mg midazolam) were given in the usual doses to achieve adequate sedation as determined by the examining physician. 80
GASTROINTESTINAL ENDOSCOPY
Figure 2. A, Subtle appearance of colon vascular ectasia. B, Deepening intensity of vessels after naloxone administration.
After a 2-minute inspection of the cecum and ascending colon, 0.4 to 0.8 mg naloxone hydrochloride were given intravenously, and drug administration was followed by another observation period. The standard dose range of naloxone was chosen for its ability to reverse the cardiopulmonary and psychomotor effects of an opiate agonist such as meperidine. In our endoscopic unit, naloxone customarily is used by all practitioners to counteract the cardiorespiratory depressant effects of meperidine. It is standard practice to give the drug either on withdrawal of the instrument or at the conclusion of the procedure, although any compromise in narcotic-induced cardiorespiratory function would prompt immediate use. Individual practitioners chose the administered dose according to their general preference. Areas of interest were photodocumented in all instances before and after administration of naloxone whether or not vascular lesions were observed. Photographs were analyzed by a reviewer for anatomic consistency, vessel appearance, morphologic similarity, size, and number and location of lesions. The reviewer, who did not participate in the procedures, was blinded to which photographs were taken before and after naloxone administration. A vasoactive response to naloxone was defined as a normal vessel VOLUME 49, NO. 1, 1999
Naloxone enhancement of colonoscopic appearance of colon vasculature
L Brandt, M Spinnell
Table 1. Indications for colonoscopy and vascular appearance before naloxone administration Total Indication Vascular Overt bleeding Occult bleeding Anemia CVEs Subtotal Nonvascular Polyps Inflammatory bowel disease Unknown Diarrhea Colon cancer Altered bowel habits Constipation Screening Subtotal Total
No CVEs
CVEs
No.
%
No.
%
No.
%
29 22 8 1 60
20 15 6 1 42
24 21 8 1 54
17 15 6 1 38
5 1 0 0 6
4 1 — — 4
31 7 27 4 7 3 3 2 84 144
22 5 19 4 5 2 2 1 58 100
26 7 23 4 7 3 3 2 75 129
18 5 16 3 5 2 2 1 52 90
5 0 4 0 0 0 0 0 9 15
4 — 3 — — — — — 6 10
or CVE that became more prominent or a CVE that appeared after naloxone administration.
one. None of the ectasias was found to bleed spontaneously after administration of naloxone.
RESULTS
DISCUSSION
One hundred forty-four patients met the inclusion criteria and were enrolled for evaluation. Indications for colonoscopy varied among subjects (Table 1). One hundred fourteen subjects (79%) had no CVEs before or after administration of naloxone. Twelve patients (8.3%) had CVEs detected at initial inspection. After naloxone administration, an additional 4 patients who were not previously found to have abnormal colonic vessels had evidence of CVEs, bringing the incidence of CVEs in the study population to 11.1%. Among these patients, 1 to 3 CVEs appeared after administration of naloxone. Six patients (4%) found to have CVEs were being examined because of overt bleeding, occult bleeding, anemia, or known CVEs. Nine patients (6%) found to have CVEs had nonvascular indications for colonoscopy (Table 1). Fourteen patients had normal colonic vessels that became more prominent after administration of naloxone. Eight patients (5.4%) had CVEs before administration of naloxone that changed after the drug was administered (Figs. 1 through 3). In 3 patients the size or intensity of the CVEs increased, in 7 the number of CVEs increased, and in 2 patients CVEs increased in size and number. Four patients with clearly visible CVEs at the initial survey had neither a change in the intensity of the vascular pattern nor an increase in number of abnormal vessels after administration of naloxone. Twenty-two patients (15.3%) had a vasoactive response to nalox-
CVEs are affected by narcotic sedation. Meperidine, a µ opiate agonist, is used commonly for sedation before colonoscopy. Meperidine has hemodynamic effects, including myocardial depression, hypotension, and decreased peripheral vascular resistance. It also activates intestinal mast cells to release histamine.8 Through these mechanisms, meperidine and similar analgesics may cause a transient decrease in mucosal blood flow that in some persons may diminish the intensity of the normal colonic vasculature or obscure the appearance of CVEs. Naloxone, an opiate antagonist, given in standard intravenous or intramuscular doses of 0.4 to 0.8 mg can prevent or reverse the effects of opiate agonists such as meperidine. Respiratory depression, hypotension, and psychomotor retardation can be reversed within 1 to 2 minutes of administration because the drug has a rapid onset of action. The duration of the antagonist effect is variable; it usually lasts 1 to 4 hours. Then the drug undergoes conjugation in the liver and is rendered inactive. Although vasodilation, or at least reversal of colonic hypoperfusion, is believed to be involved in naloxone enhancement of CVEs, it is of interest that carbon dioxide, also a vasodilator, when administered as the insufflation gas during colonoscopy, increases colon blood flow9 but does not enhance the appearance of colon vascular ectasias (L.J. Brandt, unpublished observation). Intra-arterial vasodilators such as
VOLUME 49, NO. 1, 1999
GASTROINTESTINAL ENDOSCOPY
81
A
E
B
F
C
G
D
H
Figure 3. A–H, Progressive changes in the appearance of colon vascular ectasia after administration of naloxone. The appearance of the CVE changes from a subtle, pale, pinkish blotch to a fan-shaped lesion and then evolves into a congested network of vessels. 82
GASTROINTESTINAL ENDOSCOPY
VOLUME 49, NO. 1, 1999
Naloxone enhancement of colonoscopic appearance of colon vasculature
papaverine and intravenously administered mesenteric vasodilators, including urotensin I, sauvagine, and other corticotropin-releasing factor–like peptides have been used clinically and experimentally to increase mesenteric blood flow,10,11 but their effects, if any, on CVEs have not been studied. Data from our study demonstrated that for some elderly patients undergoing colonoscopy for bleeding or a variety of other indications, administration of naloxone after narcotic sedation may increase mucosal blood flow and enhance the gross appearance of the colonic vasculature. Although photodocumentation was obtained in most instances, areas of normal mucosa in which changes (i.e., CVEs) appeared after naloxone administration were not necessarily photographed beforehand. This raises the possibility of overestimating the effect of naloxone by reporting a positive response when potentially the CVE was missed at initial inspection. Routine videography would obviate some of this bias. Nevertheless photographs clearly documented a vascular enhancing effect of naloxone. The study also could have been strengthened with an analysis of the vascular response to naloxone in the absence of prior narcotic sedation. Naloxone alone could have an effect on microvascular tissue perfusion by antagonizing endogenous opioid receptors in colonic vessels, although this has not been demonstrated in humans. Opioid receptors have been found in the colon, and various studies have shown the effect of naloxone receptor antagonism on endogenous opioids in animal models such as the rat dorsal horn ganglia.12 Naloxone might enhance the colonic vasculature and CVEs by reversing the vasoactive effect of narcotics and their action on arterial blood pressure. Although blood pressure was monitored during the entire procedure and no significant hypotensive episodes were encountered, blood pressure measurements before and after administration of naloxone were not specifically compared. Whether or not naloxone has a direct effect on the colonic microvasculature or acts by means of narcotic reversal to increase arterial blood pressure, its practical effect is to increase the diagnostic yield of colonoscopy for CVEs previously not found. Twenty-two patients (15.3%) had a vascular response to naloxone. Although a vascular change was found most often in normal blood vessels (14 patients, 9.7%), the effect on CVEs has more clinical relevance. After administration of naloxone, CVEs may become more apparent (Figs. 1 through 3). As a result, CVEs might be less likely to be overlooked, particularly in the setting of anemia or low circulating blood volume, a common scenario, particularly
VOLUME 49, NO. 1, 1999
L Brandt, M Spinnell
after serious lower intestinal hemorrhage. More impressive is the observation that naloxone caused previously unseen CVEs to “bloom.” As such, naloxone may play an important role as an adjunctive medication for elderly patients undergoing examinations for (cryptogenic) lower intestinal bleeding. Moreover, use of naloxone might be helpful in endoscopic treatment by enabling identification of lesions that otherwise might not be seen and might thus remain untreated. Additional studies are needed to verify, quantify, and further describe the utility of narcotic reversal with naloxone. In some centers, drugs that relax smooth muscle (e.g., glucagon and anticholinergics) are used to facilitate passage of a colonoscope though areas of luminal narrowing. It is conceivable that such agents might enhance the appearance of the colonic vasculature and CVEs. In summary, naloxone can enhance normal colonic vasculature, increase the vascularity of CVEs, and cause previously unseen CVEs to “bloom.” Hence naloxone may have a useful role when the cecum and ascending colon are being inspected for CVEs, especially among patients undergoing examinations for bleeding lesions in the lower intestine. REFERENCES 1. Tedesco FJ, Griffin JW Jr, Khan AQ. Vascular ectasia of the colon: clinical, colonoscopic and radiographic features. J Clin Gastroenterol 1980;2:233-8. 2. Boley S, Dibiase A, Brandt L, et al. Lower intestinal bleeding in the elderly. Am J Surg 1979;137:57-64. 3. Richter JM, Christensen MR, Colditz GA, et al. Angiodysplasia: natural history and efficacy of therapeutic interventions. Dig Dis Sci 1989;34:1542-6. 4. Richter JM, Hedberg SE, Athanasoulis CA, et al. Angiodysplasia: clinical presentation and colonoscopic diagnosis. Dig Dis Sci 1984;29:481-5. 5. Foutch PG. Angiodysplasia of the gastrointestinal tract. Am J Gastroenterol 1993;88:807-18. 6. Boley SJ, Brandt LJ. Vascular ectasias of the colon, 1986. Dig Dis Sci 1986;31:26S-42S. 7. Deal SE, Zfass AM, Duckworth PF, McHenry L. Arteriovenous malformations (AVMs): are they concealed by meperidine [abstract]? Am J Gastroenterol 1991;86:1352. 8. Huang YF, Upton RN, Rutten AJ, et al. The hemodynamic effects of intravenous bolus doses of meperidine in conscious sheep. Anesth Analg 1994;78:442-9. 9. Brandt LJ, Boley SJ, Sammartano R. Carbon dioxide and room air insufflation of the colon. Gastrointest Endosc 1986;32:324-9. 10. MacCannell KL, Comparison of an intravenous selective mesenteric vasodilator with intraarterial papaverine in experimental nonocclusive mesenteric ischemia. Gastroenterology 1986;91:79-83. 11. Boley SJ, Brandt LJ. Selective mesenteric vasodilators. Gastroenterology 1986;91:247-9. 12. Levine JD, Fields HL, Basbaum AI. Peptides and the primary afferent nociceptor. J Neurosci 1993;13:2273-86.
GASTROINTESTINAL ENDOSCOPY
83