Opiate-Induced Oesophageal Dysmotility
Opiate-Induced Oesophageal Dysmotility
Background Opiates have well characterized (troublesome) untoward effects on the gastrointestinal tract. Opioid bowel dysfunction has been a subject of research and even drug design, but surprisingly little is known with regard to clinical effects of opiates on the oesophagus.
Aim To characterize opiate effects on motor function of the oesophagus in patients presenting with dysphagia.
Methods Retrospective review of 15 patients with dysphagia referred for oesophageal manometry while on chronic opiates. Manometry was completed during opiate use and in three cases, after opiates were discontinued.
Results All patients demonstrated motility abnormalities. Incomplete lower oesophageal sphincter (LOS) relaxation (11.5 ± 1.6 mmHg) was seen in most cases. Ten patients demonstrated nonperistaltic contractions in ≥3 of 10 swallows. Additional abnormalities included high amplitude contractions; triple peaked contractions; and increased velocity. The average resting lower oesophageal sphincter (LOSP) met criteria for hypertensive LOS in three patients. These features were suggestive of spasm or achalasia. Repeat manometry off opiates was performed in three cases. LOS relaxation was noted to be complete upon repeat manometry in these cases. There was also improved peristalsis and normal velocity.
Conclusions A range of manometric abnormalities were seen in patients with dysphagia in the setting of opiate use: impaired LOS relaxation, high amplitude/velocity and simultaneous oesophageal waves. These data suggest that the oesophagus is susceptible to the effects of opiates and care must be taken before ascribing dysphagia to a primary oesophageal motility disorder in patients taking opiates.
The deleterious side effects of opiates with respect to the gastrointestinal tract have long been recognized. Much research has investigated opiates and gut dysfunction. It is well established that opioid analgesics delay intestinal transit. This occurs by stimulation of nonpropulsive contractions in the intestine and colon via both central and peripheral actions. Opioid receptors of all three classical types (μ, δ, and κ) are expressed in the central nervous system as well in the enteric nervous system. Gastrointestinal effects are most likely mediated through μ and κ receptors located on myenteric neurons, but possibly through opioid receptors on the smooth muscle itself. In the mid and distal gut, μ and κ receptors have been demonstrated within the intestinal wall. The μ receptors are most dense in the submucosal plexus on nerve terminals and κ receptors are found in greater density in the myenteric plexus. Oesophageal localization studies in humans date back to the 1980s and mostly describe LOS distribution. Opioid receptors have been demonstrated in the oesophagus, but are not as well-characterized as in the rest of the gut.
In contrast to the wealth of understanding of opioid receptor physiology regarding the stomach, small intestine and colon, far less is known about the oesophagus. Despite the paucity of knowledge of opioid receptor distribution and physiology in the human oesophagus, opiates have demonstrated clear motor effects on the human oesophagus. Physiological studies on healthy volunteers have shown that morphine decreases lower oesophageal sphincter relaxation. To date, however, there is very scarce information published on effects of opiates on the oesophagus in clinical practice. Case reports have documented acute dysphagia following intrathecal fentanyl. Retrospective series also note dysphagia with intrathecal fentanyl, suggesting a central effect. It is well known that agonists for peripheral opioid receptors are able to produce gastrointestinal effects without the central analgesic and respiratory depressant effects. It is also evident that central nervous system administration of opiates affects gastrointestinal motility as well, as intracranial administration has the same effects as peripheral administration in animals and intrathecal injections in humans have similar effects to peripheral administration. These reports of dysphagia and the known effects of oral opiates on the intestines suggest that oral opiates may affect swallow function adversely. Our aim was to characterize the manometric profile of dysphagia in patients taking opiates.
Abstract and Introduction
Abstract
Background Opiates have well characterized (troublesome) untoward effects on the gastrointestinal tract. Opioid bowel dysfunction has been a subject of research and even drug design, but surprisingly little is known with regard to clinical effects of opiates on the oesophagus.
Aim To characterize opiate effects on motor function of the oesophagus in patients presenting with dysphagia.
Methods Retrospective review of 15 patients with dysphagia referred for oesophageal manometry while on chronic opiates. Manometry was completed during opiate use and in three cases, after opiates were discontinued.
Results All patients demonstrated motility abnormalities. Incomplete lower oesophageal sphincter (LOS) relaxation (11.5 ± 1.6 mmHg) was seen in most cases. Ten patients demonstrated nonperistaltic contractions in ≥3 of 10 swallows. Additional abnormalities included high amplitude contractions; triple peaked contractions; and increased velocity. The average resting lower oesophageal sphincter (LOSP) met criteria for hypertensive LOS in three patients. These features were suggestive of spasm or achalasia. Repeat manometry off opiates was performed in three cases. LOS relaxation was noted to be complete upon repeat manometry in these cases. There was also improved peristalsis and normal velocity.
Conclusions A range of manometric abnormalities were seen in patients with dysphagia in the setting of opiate use: impaired LOS relaxation, high amplitude/velocity and simultaneous oesophageal waves. These data suggest that the oesophagus is susceptible to the effects of opiates and care must be taken before ascribing dysphagia to a primary oesophageal motility disorder in patients taking opiates.
Introduction
The deleterious side effects of opiates with respect to the gastrointestinal tract have long been recognized. Much research has investigated opiates and gut dysfunction. It is well established that opioid analgesics delay intestinal transit. This occurs by stimulation of nonpropulsive contractions in the intestine and colon via both central and peripheral actions. Opioid receptors of all three classical types (μ, δ, and κ) are expressed in the central nervous system as well in the enteric nervous system. Gastrointestinal effects are most likely mediated through μ and κ receptors located on myenteric neurons, but possibly through opioid receptors on the smooth muscle itself. In the mid and distal gut, μ and κ receptors have been demonstrated within the intestinal wall. The μ receptors are most dense in the submucosal plexus on nerve terminals and κ receptors are found in greater density in the myenteric plexus. Oesophageal localization studies in humans date back to the 1980s and mostly describe LOS distribution. Opioid receptors have been demonstrated in the oesophagus, but are not as well-characterized as in the rest of the gut.
In contrast to the wealth of understanding of opioid receptor physiology regarding the stomach, small intestine and colon, far less is known about the oesophagus. Despite the paucity of knowledge of opioid receptor distribution and physiology in the human oesophagus, opiates have demonstrated clear motor effects on the human oesophagus. Physiological studies on healthy volunteers have shown that morphine decreases lower oesophageal sphincter relaxation. To date, however, there is very scarce information published on effects of opiates on the oesophagus in clinical practice. Case reports have documented acute dysphagia following intrathecal fentanyl. Retrospective series also note dysphagia with intrathecal fentanyl, suggesting a central effect. It is well known that agonists for peripheral opioid receptors are able to produce gastrointestinal effects without the central analgesic and respiratory depressant effects. It is also evident that central nervous system administration of opiates affects gastrointestinal motility as well, as intracranial administration has the same effects as peripheral administration in animals and intrathecal injections in humans have similar effects to peripheral administration. These reports of dysphagia and the known effects of oral opiates on the intestines suggest that oral opiates may affect swallow function adversely. Our aim was to characterize the manometric profile of dysphagia in patients taking opiates.
