Pre-Emptive Analgesia in Ano-Rectal Surgery
| Status: | Completed |
|---|---|
| Conditions: | Hospital, Gastrointestinal, Gastrointestinal |
| Therapuetic Areas: | Gastroenterology, Other |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 1/17/2018 |
| Start Date: | June 2014 |
| End Date: | May 2017 |
The perianal region is the region around the anus. Administering a pain medication before a
surgery starts is called preemptive analgesia. In some studies, this technique has been shown
to be an effective way to reduce the pain that a patient experiences in the post-operative
timeframe to a greater extent than would be expected simply from the pain medications alone.
One theory of why this occurs suggests that the preemptive analgesia desensitizes brain and
nerves to pain, thereby decreasing the response to painful stimuli, like surgery when they
occur. This leads to a decrease in the amount of narcotic pain medication required after the
procedure, which leads to less side effects and a quicker return to normal functioning. As
perianal surgeries do not usually include a long stay in the hospital, controlling
post-procedure pain is a priority.
The use of preemptive analgesia is in other types of surgeries, such as orthopedics, is well
established, but as the perianal region has not been well studied, its use is not the
standard of care. This type of analgesia uses a combination of medications that are already
in use for post-operative and non-operative pain control and administers them orally prior to
the patient undergoing general anesthesia. The side effects of the medications are the same
as if they had been given after surgery or for non-surgical pain.
The concept of preemptive analgesia is established in other types of surgeries and it has
solid basic science to support its use. The purpose of this randomized, double-blind, placebo
controlled study is to determine if patients undergoing perianal surgeries could benefit from
preemptive pain control. The primary outcome will be whether patients experience less
post-operative pain. Patient post-operative consumption and latency until use of narcotic
pain medication will be the secondary outcomes. The investigators believe that the patients
receiving pain medications before their operation will require less pain medication after
surgery, with minimal increased risk to the patient.
surgery starts is called preemptive analgesia. In some studies, this technique has been shown
to be an effective way to reduce the pain that a patient experiences in the post-operative
timeframe to a greater extent than would be expected simply from the pain medications alone.
One theory of why this occurs suggests that the preemptive analgesia desensitizes brain and
nerves to pain, thereby decreasing the response to painful stimuli, like surgery when they
occur. This leads to a decrease in the amount of narcotic pain medication required after the
procedure, which leads to less side effects and a quicker return to normal functioning. As
perianal surgeries do not usually include a long stay in the hospital, controlling
post-procedure pain is a priority.
The use of preemptive analgesia is in other types of surgeries, such as orthopedics, is well
established, but as the perianal region has not been well studied, its use is not the
standard of care. This type of analgesia uses a combination of medications that are already
in use for post-operative and non-operative pain control and administers them orally prior to
the patient undergoing general anesthesia. The side effects of the medications are the same
as if they had been given after surgery or for non-surgical pain.
The concept of preemptive analgesia is established in other types of surgeries and it has
solid basic science to support its use. The purpose of this randomized, double-blind, placebo
controlled study is to determine if patients undergoing perianal surgeries could benefit from
preemptive pain control. The primary outcome will be whether patients experience less
post-operative pain. Patient post-operative consumption and latency until use of narcotic
pain medication will be the secondary outcomes. The investigators believe that the patients
receiving pain medications before their operation will require less pain medication after
surgery, with minimal increased risk to the patient.
Despite advances in pain medicine, postoperative pain control remains problematic with over
5% of patients experiencing severe pain despite standard of care pain management, and is a
frequently cited reason for delayed discharge in outpatient procedures [1]. In anorectal
surgeries, almost all patients experience mild-to-moderate postoperative subjective pain [2],
and as an example 12% of patients report severe postoperative pain during their recovery from
hemorrhoidectomy surgery [3]. Control of postoperative pain is an important goal. Preemptive
analgesia is a technique that involves premedicating the patient with a regimen of
medications designed to target different points in the pain cascade to prevent central and
peripheral sensitization to pain, also known as "wind-up" [4]. The activation of
N-methyl-D-aspartate (NMDA) receptors is an identified process that occurs in central
sensitization after a noxious stimulus. By pharmacologically blocking these receptors, it may
be possible to prevent or suppress the degree of central sensitization, which can prevent the
hyperalgesic, or exaggerated pain response, that some patients experience [5]. Peripheral
sensitization is a similar concept and occurs due to noxious stimuli in the periphery, such
as a surgical incision. This type of sensitization has typically been prevented with regional
anesthesia and by increasing the nociceptive threshold of the neurons with different
medications.
Preemptive analgesia focusing on the effect of single medications on pain control has shown
promising results, however some studies appear to lend themselves to practice [6-19] better
than others [20-26]. On the other hand, multimodal pain control regimens might be more
promising. A search of the literature reveals that preemptive pharmacological blockade of
wind up has been effectively used in both surgical and nonsurgical patients (burn patients
[27]). In patients undergoing hip arthroplasty, or hip replacement surgery, under general
anesthesia, blocking both central and peripheral sensitization results in significantly
decreased subjective pain, and a trend toward less postoperative use of analgesics [28].
Similarly, patients undergoing multilevel spinal surgeries [29] and those undergoing
prostatic surgery [30] under general anesthesia consume less postoperative analgesics when
undergoing multimodal preemptive pain control by blocking both sensitization pathways.
Finally, preemptive central sensitization blockade alone has been used with trends in
improved pain control for gynecological surgeries under both general [31] and regional
anesthesia [32]. The preemptive use of such medications has not been studied for anorectal
surgeries and it is what we are suggesting in this study. Most pain control studies in the
literature focus on postoperative rather than preemptive medication regimens for pain
management [33-35], and there is no current standard of care as to an effective regimen. The
studies effective in decreasing postoperative pain in other surgical contexts, such as for
patients undergoing hip arthroplasty, have used the same combination of medications proposed
for the Treatment Group. Finally, the added benefit of the anorectal patient population in
terms of the putative decreased use of opioids for postoperative pain control revolves around
the opioid-related adverse effects on bowel function. In fact, return of bowel movements and
regularity is one criterion for healing after surgery.
Based on this existing literature, we propose in our current study to preemptively block both
central sensitization through the use of intravenous ketamine perioperatively and peripheral
sensitization through the use of intravenous dexamethasone administered perioperatively and
oral gabapentin and acetaminophen administered preoperatively. Ketamine is a noncompetitive
NMDA receptor antagonist acting centrally in the dorsal horn of the spinal cord to decrease
the release of glutamate, reducing the transmission of pain messages centrally [36].
Intravenous ketamine has been shown to decrease 24-hour opioid requirements, and preemptive
use of ketamine was part of the medications used in most of the studies mentioned in the
literature review above. As it currently stands, use of ketamine in anorectal surgeries as an
added analgesic has been proven safe. Among Nigerian surgery patients having received
regional anesthesia and preemptive ketamine, postoperative pain levels have been shown to
decrease, however it is unclear if this patient cohort included anorectal surgery patients
[37]. No other studies have been conducted regarding postoperative pain in these patients
[38]. By utilizing ketamine as one of the medications in our study, we hope to show similar
effects resulting in patients experiencing decreased postoperative pain after common
anorectal surgeries.
Dexamethasone is a corticosteroid with potent anti-inflammatory effects that is also used as
an anti-emetic. The proposed mechanism of action of dexamethasone is not completely known,
but it is thought to involve inhibition of prostaglandin synthesis and an increased release
of endorphins. Endorphins are endogenous peptides that bind to pain receptors in the body to
decrease pain. In addition, endorphins can facilitate mood elevation and a sense of
well-being. Intravenous dexamethasone was part of the medications used in studies mentioned
in the literature review above. One study investigating the prophylactic use of dexamethasone
for its anti-emetic properties, in combination with sevoflurane, a general anesthetic, during
anorectal surgery found a significant decrease in maximal postoperative VAS pain scores in
patients administered dexamethasone compared to those given placebos [2]. The use of
dexamethasone as a preemptive analgesic has not been fully studied in anorectal surgery
patients.
Gabapentin acts by binding to receptors on voltage-gated calcium channels on presynaptic
nerves, reducing the entry of calcium into presynaptic nerve terminals. The subsequent
decreased release of excitatory neurotransmitters such as glutamate, aspartate, substance P,
and norepinephrine into the synaptic cleft is linked to a diminished postsynaptic
transmission of neural pain messages [36]. It is usually used for neuropathic pain control,
and has been used in some of the studies mentioned in the literature review above. A systemic
review of the perioperative effects of gabapentin found that it is an effective means of
reducing post-operative pain, opioid consumption, and opioid-related adverse effects in
surgical patients. In fact, administration of a single dose of gabapentin was found to be
equivalent to a reduction of 30 mg of morphine in the first 24 hours after surgery [39]. No
studies have been conducted, to the best of our knowledge, regarding preemptive use of
gabapentin in anorectal surgeries.
Local, peripheral sensitization has also been minimized through the use of non-steroidal
anti-inflammatory drugs (NSAIDs) due to the decreased production of certain molecules such as
prostaglandins and kinins. The enzyme required to make these molecules is blocked by
acetaminophen and NSAIDs, which is why acetaminophen is included in this study in hopes of
demonstrating better pain control among anorectal surgery patients. Acetaminophen is a weak
analgesic that forms the most basic component of a multimodal analgesia regimen [36]. Oral
preemptive use of acetaminophen has been proven to decrease postoperative narcotic use in
surgical patients [40], and has been used in some of the studies mentioned in the literature
review above. A related intramuscular NSAID, namely Toradol, has been used preemptively among
anorectal surgical patients with good pain control [41]. No other studies are reported in
this patient population.
Of importance, the combinations of the medications used in this study have been used in other
studies before with similar or higher doses and no significant differences in terms of
hemodynamic variables (such as vital signs) or adverse side effects have been noted compared
to control groups [31]. In fact, these medications are safely used at UVM Medical Center by
the collaborating surgeons as part of their care for other surgeries such as abdominal
surgeries.
*References 1-41 available upon request
5% of patients experiencing severe pain despite standard of care pain management, and is a
frequently cited reason for delayed discharge in outpatient procedures [1]. In anorectal
surgeries, almost all patients experience mild-to-moderate postoperative subjective pain [2],
and as an example 12% of patients report severe postoperative pain during their recovery from
hemorrhoidectomy surgery [3]. Control of postoperative pain is an important goal. Preemptive
analgesia is a technique that involves premedicating the patient with a regimen of
medications designed to target different points in the pain cascade to prevent central and
peripheral sensitization to pain, also known as "wind-up" [4]. The activation of
N-methyl-D-aspartate (NMDA) receptors is an identified process that occurs in central
sensitization after a noxious stimulus. By pharmacologically blocking these receptors, it may
be possible to prevent or suppress the degree of central sensitization, which can prevent the
hyperalgesic, or exaggerated pain response, that some patients experience [5]. Peripheral
sensitization is a similar concept and occurs due to noxious stimuli in the periphery, such
as a surgical incision. This type of sensitization has typically been prevented with regional
anesthesia and by increasing the nociceptive threshold of the neurons with different
medications.
Preemptive analgesia focusing on the effect of single medications on pain control has shown
promising results, however some studies appear to lend themselves to practice [6-19] better
than others [20-26]. On the other hand, multimodal pain control regimens might be more
promising. A search of the literature reveals that preemptive pharmacological blockade of
wind up has been effectively used in both surgical and nonsurgical patients (burn patients
[27]). In patients undergoing hip arthroplasty, or hip replacement surgery, under general
anesthesia, blocking both central and peripheral sensitization results in significantly
decreased subjective pain, and a trend toward less postoperative use of analgesics [28].
Similarly, patients undergoing multilevel spinal surgeries [29] and those undergoing
prostatic surgery [30] under general anesthesia consume less postoperative analgesics when
undergoing multimodal preemptive pain control by blocking both sensitization pathways.
Finally, preemptive central sensitization blockade alone has been used with trends in
improved pain control for gynecological surgeries under both general [31] and regional
anesthesia [32]. The preemptive use of such medications has not been studied for anorectal
surgeries and it is what we are suggesting in this study. Most pain control studies in the
literature focus on postoperative rather than preemptive medication regimens for pain
management [33-35], and there is no current standard of care as to an effective regimen. The
studies effective in decreasing postoperative pain in other surgical contexts, such as for
patients undergoing hip arthroplasty, have used the same combination of medications proposed
for the Treatment Group. Finally, the added benefit of the anorectal patient population in
terms of the putative decreased use of opioids for postoperative pain control revolves around
the opioid-related adverse effects on bowel function. In fact, return of bowel movements and
regularity is one criterion for healing after surgery.
Based on this existing literature, we propose in our current study to preemptively block both
central sensitization through the use of intravenous ketamine perioperatively and peripheral
sensitization through the use of intravenous dexamethasone administered perioperatively and
oral gabapentin and acetaminophen administered preoperatively. Ketamine is a noncompetitive
NMDA receptor antagonist acting centrally in the dorsal horn of the spinal cord to decrease
the release of glutamate, reducing the transmission of pain messages centrally [36].
Intravenous ketamine has been shown to decrease 24-hour opioid requirements, and preemptive
use of ketamine was part of the medications used in most of the studies mentioned in the
literature review above. As it currently stands, use of ketamine in anorectal surgeries as an
added analgesic has been proven safe. Among Nigerian surgery patients having received
regional anesthesia and preemptive ketamine, postoperative pain levels have been shown to
decrease, however it is unclear if this patient cohort included anorectal surgery patients
[37]. No other studies have been conducted regarding postoperative pain in these patients
[38]. By utilizing ketamine as one of the medications in our study, we hope to show similar
effects resulting in patients experiencing decreased postoperative pain after common
anorectal surgeries.
Dexamethasone is a corticosteroid with potent anti-inflammatory effects that is also used as
an anti-emetic. The proposed mechanism of action of dexamethasone is not completely known,
but it is thought to involve inhibition of prostaglandin synthesis and an increased release
of endorphins. Endorphins are endogenous peptides that bind to pain receptors in the body to
decrease pain. In addition, endorphins can facilitate mood elevation and a sense of
well-being. Intravenous dexamethasone was part of the medications used in studies mentioned
in the literature review above. One study investigating the prophylactic use of dexamethasone
for its anti-emetic properties, in combination with sevoflurane, a general anesthetic, during
anorectal surgery found a significant decrease in maximal postoperative VAS pain scores in
patients administered dexamethasone compared to those given placebos [2]. The use of
dexamethasone as a preemptive analgesic has not been fully studied in anorectal surgery
patients.
Gabapentin acts by binding to receptors on voltage-gated calcium channels on presynaptic
nerves, reducing the entry of calcium into presynaptic nerve terminals. The subsequent
decreased release of excitatory neurotransmitters such as glutamate, aspartate, substance P,
and norepinephrine into the synaptic cleft is linked to a diminished postsynaptic
transmission of neural pain messages [36]. It is usually used for neuropathic pain control,
and has been used in some of the studies mentioned in the literature review above. A systemic
review of the perioperative effects of gabapentin found that it is an effective means of
reducing post-operative pain, opioid consumption, and opioid-related adverse effects in
surgical patients. In fact, administration of a single dose of gabapentin was found to be
equivalent to a reduction of 30 mg of morphine in the first 24 hours after surgery [39]. No
studies have been conducted, to the best of our knowledge, regarding preemptive use of
gabapentin in anorectal surgeries.
Local, peripheral sensitization has also been minimized through the use of non-steroidal
anti-inflammatory drugs (NSAIDs) due to the decreased production of certain molecules such as
prostaglandins and kinins. The enzyme required to make these molecules is blocked by
acetaminophen and NSAIDs, which is why acetaminophen is included in this study in hopes of
demonstrating better pain control among anorectal surgery patients. Acetaminophen is a weak
analgesic that forms the most basic component of a multimodal analgesia regimen [36]. Oral
preemptive use of acetaminophen has been proven to decrease postoperative narcotic use in
surgical patients [40], and has been used in some of the studies mentioned in the literature
review above. A related intramuscular NSAID, namely Toradol, has been used preemptively among
anorectal surgical patients with good pain control [41]. No other studies are reported in
this patient population.
Of importance, the combinations of the medications used in this study have been used in other
studies before with similar or higher doses and no significant differences in terms of
hemodynamic variables (such as vital signs) or adverse side effects have been noted compared
to control groups [31]. In fact, these medications are safely used at UVM Medical Center by
the collaborating surgeons as part of their care for other surgeries such as abdominal
surgeries.
*References 1-41 available upon request
Inclusion Criteria:
- Patients having anal fistula repairs for anal fistulas recalcitrant to non-surgical
management at the University of Vermont Medical Center or Fanny Allen Campuses OR
- Patients having anal sphincterotomies for chronic anal fissures recalcitrant to
non-surgical management at the University of Vermont Medical Center or Fanny Allen
Campuses OR
- Patients having hemorrhoidectomies for hemorrhoids recalcitrant to non-surgical
management at the University of Vermont Medical Center or Fanny Allen Campuses OR
- Patients having anal condyloma excisions for anal condylomas recalcitrant to
non-surgical management at the University of Vermont Medical Center or Fanny Allen
Campuses
- Patients undergoing these surgeries must be American Society of Anesthesiologists
(ASA) Physical Status Classification System scores of I (normal, healthy patient), II
(patient with mild, systemic disease), or III (patients with more significant disease)
Exclusion Criteria:
- Allergies to any study medications;
- Patient history and chart review for existence of hepatic or renal failure;
- Chronic pain syndrome;
- Inability to understand or utilize the Numerical Rating Scale (NRS);
- Pregnancy;
- Patients currently on gabapentin, pregabalin or narcotics
- Patients taking chronic steroids, unable to taper off before surgery
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