Make the most of nonopioids: Managing acute pain in children

ORLANDO – Effective management of acute pain in children is important not only for improving comfort, but also for improving outcomes, according to Dr. Joseph D. Tobias.

"The important thing to realize is that there are many benefits (of pain management). Although we walk a fine line between adverse effects and benefits, many times with adequate analgesia we put patients in a better place, Dr. Tobias, chief of anesthesiology and pain medicine at Nationwide Children’s Hospital in Columbus, Ohio, said at the annual meeting of the American Academy of Pediatrics.

That’s because with inadequate analgesia there are a host of humoral factors, including increased endogenous catecholamines, that have adverse physiologic effects on oxygen consumption, CO₂ production, and on the immune system, he explained.

Multiple studies have demonstrated that aggressive pain management has beneficial immune effects, he added, noting that patients with adequate pain management are less likely to experience infections and that neonates and infants without adequate pain management may experience chronic pain and pain syndromes later in life because of the neuroplasticity of the infant brain.

He recommends the classic "stepwise ladder" approach to pain management in pediatric patients with acute pain following surgery, trauma, or acute illness, for example. Step 1 involves administration of nonopioids and adjuvants.

"But even as we move to step 2 and add opioids, it’s very important to keep the nonopioids and adjuvants going. I don’t think anybody should ever be in the hospital on [patient-controlled analgesia] getting opioids and not getting nonsteroidal [drugs], acetaminophen, and other adjuvants, because what you’re going to do is decrease your opioid requirements, and as you do that, you then decrease opioid-related side effects," he said.

Keep in mind that the maximum dose of oral or rectal acetaminophen has been decreased from 4 to 3 grams, he said, noting that reports of significant toxicity with acetaminophen have been increasing, so it is important to limit the dose.

The same holds true for the new intravenous preparation of acetaminophen, given reports of 10-fold overdose (10 mg/mL concentration).

"We need to be cognizant of that," he said.

A number of salicylates and NSAIDs are also available for use in children. Ibuprofen is among the most commonly used, and also is now available in an intravenous formulation.

Ketorolac is another good treatment option, but intravenous acetaminophen is preferable in children under age 1 year, because of concerns regarding decreased renal perfusion, he said.

Other emerging options that are making their way from the adult to the pediatric pain-management arena are ketamine, gabapentin and pregabalin, dexamethasone, and dexmedetomidine, all of which appear to have some potential benefits for improving pain management and reducing the need for opioids.

Watch for interactions and adverse effects

Be sure to assess for potential drug interactions in children on several medications and to protect against the adverse gastrointestinal tract effects of nonsteroidal drugs, Dr. Tobias advised.

"If you’re using nonsteroidals, especially postoperatively in patients, it’s always a good idea to combine them with a proton pump inhibitor, or an H2 antagonist," he said, noting that that these can generally be discontinued once the patient is tolerating a regular diet.

Effects on renal function are also an important concern, particularly in those with preexisting renal dysfunction, concomitant use of other nephrotoxic agents, hypovolemia, hypoperfusion, and prolonged administration.

Bleeding is another concern, particularly in those receiving ketorolac, which shouldn’t be used in children undergoing tonsillectomy or in other cases involving increased bleeding risk, he said.

As for opioids, morphine and hydromorphone are the most commonly used in children, accounting for about 99% of usage.

Morphine is more often associated with pruritus in older children and adolescents, so hydromorphone may be a better option to start with in these patients.

"As far as dosing guidelines, I think it’s very important to adjust the dose based on the patient’s status and follow pain scores. I think everybody in the hospital needs to have their pain score checked. It doesn’t matter which (pain scale) you use," Dr. Tobias said.

Also, a steady-state serum concentration should be maintained with avoidance of peaks and troughs, and patients on opioids should be monitored for adverse effects, he said, noting that patient-controlled analgesia (PCA) devices are useful – after a loading dose – to maintain those concentrations. PCA devices can be used by children as young as 5 or 6 years of age; nurse-controlled analgesia is best for those who are younger or have cognitive impairment.

A lower basal infusion rate (4-5 mcg/kg per hour) allows for better sleep while reducing side effects, he said.

Among the concerning side effects of opioids are constipation and respiratory depression.

"Remember, you develop tolerance least quickly to their effects on the GI tract ... when you’re sending kids home from the hospital on opioids, make sure you focus on their bowel habits, or they’re going to be back, they’re going to be constipated, they’re not going to be ambulating, they may not be as well hydrated, so we really need to focus on the GI tract," he said.

Respiratory depression is recognized as an increasing concern.

"When these kids are getting PCA on the floor, make sure you have ready access to resuscitation equipment should you need it," he said.

"Especially as the population gets bigger, we may have more undiagnosed OSA [obstructive sleep apnea], so all of our patients get their respiratory rates checked, they’re on pulse oximetry. In really high-risk patients, we’re using end tidal transcutaneous CO₂ monitoring," he said, adding: "Remember, hypoxemia is a late finding of opioid-related respiratory depression. You’re going to see a slight elevation in carbon dioxide first."

Adverse effects are most common in those at the extremes of age, in those with underlying systemic diseases, and in those receiving other agents that are central nervous system depressants.

Of course, the best way to limit side effects is to use adjunctive agents, Dr. Tobias said.

"Maximize the use of nonsteroidals and acetaminophen, and you’re going to use a lot less opioid," he said.

Another important approach to reducing opioid use is the perioperative use of regional anesthesia.

"If you’re working in the hospital taking care of kids after major surgical procedures, I think if you partner with the anesthesia team there’s a lot you can do perioperatively to almost eliminate the need for intravenous opioids," he said.

For a femur fracture patient, for example, a catheter can be placed near the femoral nerve to provide analgesia, or the lateral femoral cutaneous nerve can be blocked. Ultrasound has "really opened the door for regional anesthesia."

Home infusion devices are also available.

"So if you’re having your anterior cruciate ligament repaired, where I work, you’re going to go home with a femoral nerve catheter and a home infusion device that will work for 3 days and really limit your need for parenteral and oral opioids," he said.

Outside of the operating room, regional anesthesia can be used to treat pain that is unresponsive to opioids or if the opioids are causing side effects. Cases involving sickle cell vaso-occlusive crisis, multiple trauma, or burns are scenarios in which regional anesthesia can be particularly useful, he said.

Dr. Tobias reported having no disclosures.

ORLANDO – Effective management of acute pain in children is important not only for improving comfort, but also for improving outcomes, according to Dr. Joseph D. Tobias.

"The important thing to realize is that there are many benefits (of pain management). Although we walk a fine line between adverse effects and benefits, many times with adequate analgesia we put patients in a better place, Dr. Tobias, chief of anesthesiology and pain medicine at Nationwide Children’s Hospital in Columbus, Ohio, said at the annual meeting of the American Academy of Pediatrics.

That’s because with inadequate analgesia there are a host of humoral factors, including increased endogenous catecholamines, that have adverse physiologic effects on oxygen consumption, CO₂ production, and on the immune system, he explained.

Multiple studies have demonstrated that aggressive pain management has beneficial immune effects, he added, noting that patients with adequate pain management are less likely to experience infections and that neonates and infants without adequate pain management may experience chronic pain and pain syndromes later in life because of the neuroplasticity of the infant brain.

He recommends the classic "stepwise ladder" approach to pain management in pediatric patients with acute pain following surgery, trauma, or acute illness, for example. Step 1 involves administration of nonopioids and adjuvants.

"But even as we move to step 2 and add opioids, it’s very important to keep the nonopioids and adjuvants going. I don’t think anybody should ever be in the hospital on [patient-controlled analgesia] getting opioids and not getting nonsteroidal [drugs], acetaminophen, and other adjuvants, because what you’re going to do is decrease your opioid requirements, and as you do that, you then decrease opioid-related side effects," he said.

Keep in mind that the maximum dose of oral or rectal acetaminophen has been decreased from 4 to 3 grams, he said, noting that reports of significant toxicity with acetaminophen have been increasing, so it is important to limit the dose.

The same holds true for the new intravenous preparation of acetaminophen, given reports of 10-fold overdose (10 mg/mL concentration).

"We need to be cognizant of that," he said.

A number of salicylates and NSAIDs are also available for use in children. Ibuprofen is among the most commonly used, and also is now available in an intravenous formulation.

Ketorolac is another good treatment option, but intravenous acetaminophen is preferable in children under age 1 year, because of concerns regarding decreased renal perfusion, he said.

Other emerging options that are making their way from the adult to the pediatric pain-management arena are ketamine, gabapentin and pregabalin, dexamethasone, and dexmedetomidine, all of which appear to have some potential benefits for improving pain management and reducing the need for opioids.

Watch for interactions and adverse effects

Be sure to assess for potential drug interactions in children on several medications and to protect against the adverse gastrointestinal tract effects of nonsteroidal drugs, Dr. Tobias advised.

"If you’re using nonsteroidals, especially postoperatively in patients, it’s always a good idea to combine them with a proton pump inhibitor, or an H2 antagonist," he said, noting that that these can generally be discontinued once the patient is tolerating a regular diet.

Effects on renal function are also an important concern, particularly in those with preexisting renal dysfunction, concomitant use of other nephrotoxic agents, hypovolemia, hypoperfusion, and prolonged administration.

Bleeding is another concern, particularly in those receiving ketorolac, which shouldn’t be used in children undergoing tonsillectomy or in other cases involving increased bleeding risk, he said.

As for opioids, morphine and hydromorphone are the most commonly used in children, accounting for about 99% of usage.

Morphine is more often associated with pruritus in older children and adolescents, so hydromorphone may be a better option to start with in these patients.

"As far as dosing guidelines, I think it’s very important to adjust the dose based on the patient’s status and follow pain scores. I think everybody in the hospital needs to have their pain score checked. It doesn’t matter which (pain scale) you use," Dr. Tobias said.

Also, a steady-state serum concentration should be maintained with avoidance of peaks and troughs, and patients on opioids should be monitored for adverse effects, he said, noting that patient-controlled analgesia (PCA) devices are useful – after a loading dose – to maintain those concentrations. PCA devices can be used by children as young as 5 or 6 years of age; nurse-controlled analgesia is best for those who are younger or have cognitive impairment.

A lower basal infusion rate (4-5 mcg/kg per hour) allows for better sleep while reducing side effects, he said.

Among the concerning side effects of opioids are constipation and respiratory depression.

"Remember, you develop tolerance least quickly to their effects on the GI tract ... when you’re sending kids home from the hospital on opioids, make sure you focus on their bowel habits, or they’re going to be back, they’re going to be constipated, they’re not going to be ambulating, they may not be as well hydrated, so we really need to focus on the GI tract," he said.

Respiratory depression is recognized as an increasing concern.

"When these kids are getting PCA on the floor, make sure you have ready access to resuscitation equipment should you need it," he said.

"Especially as the population gets bigger, we may have more undiagnosed OSA [obstructive sleep apnea], so all of our patients get their respiratory rates checked, they’re on pulse oximetry. In really high-risk patients, we’re using end tidal transcutaneous CO₂ monitoring," he said, adding: "Remember, hypoxemia is a late finding of opioid-related respiratory depression. You’re going to see a slight elevation in carbon dioxide first."

Adverse effects are most common in those at the extremes of age, in those with underlying systemic diseases, and in those receiving other agents that are central nervous system depressants.

Of course, the best way to limit side effects is to use adjunctive agents, Dr. Tobias said.

"Maximize the use of nonsteroidals and acetaminophen, and you’re going to use a lot less opioid," he said.

Another important approach to reducing opioid use is the perioperative use of regional anesthesia.

"If you’re working in the hospital taking care of kids after major surgical procedures, I think if you partner with the anesthesia team there’s a lot you can do perioperatively to almost eliminate the need for intravenous opioids," he said.

For a femur fracture patient, for example, a catheter can be placed near the femoral nerve to provide analgesia, or the lateral femoral cutaneous nerve can be blocked. Ultrasound has "really opened the door for regional anesthesia."

Home infusion devices are also available.

"So if you’re having your anterior cruciate ligament repaired, where I work, you’re going to go home with a femoral nerve catheter and a home infusion device that will work for 3 days and really limit your need for parenteral and oral opioids," he said.

Outside of the operating room, regional anesthesia can be used to treat pain that is unresponsive to opioids or if the opioids are causing side effects. Cases involving sickle cell vaso-occlusive crisis, multiple trauma, or burns are scenarios in which regional anesthesia can be particularly useful, he said.

Dr. Tobias reported having no disclosures.

ORLANDO – Effective management of acute pain in children is important not only for improving comfort, but also for improving outcomes, according to Dr. Joseph D. Tobias.

"The important thing to realize is that there are many benefits (of pain management). Although we walk a fine line between adverse effects and benefits, many times with adequate analgesia we put patients in a better place, Dr. Tobias, chief of anesthesiology and pain medicine at Nationwide Children’s Hospital in Columbus, Ohio, said at the annual meeting of the American Academy of Pediatrics.

That’s because with inadequate analgesia there are a host of humoral factors, including increased endogenous catecholamines, that have adverse physiologic effects on oxygen consumption, CO₂ production, and on the immune system, he explained.

Multiple studies have demonstrated that aggressive pain management has beneficial immune effects, he added, noting that patients with adequate pain management are less likely to experience infections and that neonates and infants without adequate pain management may experience chronic pain and pain syndromes later in life because of the neuroplasticity of the infant brain.

He recommends the classic "stepwise ladder" approach to pain management in pediatric patients with acute pain following surgery, trauma, or acute illness, for example. Step 1 involves administration of nonopioids and adjuvants.

"But even as we move to step 2 and add opioids, it’s very important to keep the nonopioids and adjuvants going. I don’t think anybody should ever be in the hospital on [patient-controlled analgesia] getting opioids and not getting nonsteroidal [drugs], acetaminophen, and other adjuvants, because what you’re going to do is decrease your opioid requirements, and as you do that, you then decrease opioid-related side effects," he said.

Keep in mind that the maximum dose of oral or rectal acetaminophen has been decreased from 4 to 3 grams, he said, noting that reports of significant toxicity with acetaminophen have been increasing, so it is important to limit the dose.

The same holds true for the new intravenous preparation of acetaminophen, given reports of 10-fold overdose (10 mg/mL concentration).

"We need to be cognizant of that," he said.

A number of salicylates and NSAIDs are also available for use in children. Ibuprofen is among the most commonly used, and also is now available in an intravenous formulation.

Ketorolac is another good treatment option, but intravenous acetaminophen is preferable in children under age 1 year, because of concerns regarding decreased renal perfusion, he said.

Other emerging options that are making their way from the adult to the pediatric pain-management arena are ketamine, gabapentin and pregabalin, dexamethasone, and dexmedetomidine, all of which appear to have some potential benefits for improving pain management and reducing the need for opioids.

Watch for interactions and adverse effects

Be sure to assess for potential drug interactions in children on several medications and to protect against the adverse gastrointestinal tract effects of nonsteroidal drugs, Dr. Tobias advised.

"If you’re using nonsteroidals, especially postoperatively in patients, it’s always a good idea to combine them with a proton pump inhibitor, or an H2 antagonist," he said, noting that that these can generally be discontinued once the patient is tolerating a regular diet.

Effects on renal function are also an important concern, particularly in those with preexisting renal dysfunction, concomitant use of other nephrotoxic agents, hypovolemia, hypoperfusion, and prolonged administration.

Bleeding is another concern, particularly in those receiving ketorolac, which shouldn’t be used in children undergoing tonsillectomy or in other cases involving increased bleeding risk, he said.

As for opioids, morphine and hydromorphone are the most commonly used in children, accounting for about 99% of usage.

Morphine is more often associated with pruritus in older children and adolescents, so hydromorphone may be a better option to start with in these patients.

"As far as dosing guidelines, I think it’s very important to adjust the dose based on the patient’s status and follow pain scores. I think everybody in the hospital needs to have their pain score checked. It doesn’t matter which (pain scale) you use," Dr. Tobias said.

Also, a steady-state serum concentration should be maintained with avoidance of peaks and troughs, and patients on opioids should be monitored for adverse effects, he said, noting that patient-controlled analgesia (PCA) devices are useful – after a loading dose – to maintain those concentrations. PCA devices can be used by children as young as 5 or 6 years of age; nurse-controlled analgesia is best for those who are younger or have cognitive impairment.

A lower basal infusion rate (4-5 mcg/kg per hour) allows for better sleep while reducing side effects, he said.

Among the concerning side effects of opioids are constipation and respiratory depression.

"Remember, you develop tolerance least quickly to their effects on the GI tract ... when you’re sending kids home from the hospital on opioids, make sure you focus on their bowel habits, or they’re going to be back, they’re going to be constipated, they’re not going to be ambulating, they may not be as well hydrated, so we really need to focus on the GI tract," he said.

Respiratory depression is recognized as an increasing concern.

"When these kids are getting PCA on the floor, make sure you have ready access to resuscitation equipment should you need it," he said.

"Especially as the population gets bigger, we may have more undiagnosed OSA [obstructive sleep apnea], so all of our patients get their respiratory rates checked, they’re on pulse oximetry. In really high-risk patients, we’re using end tidal transcutaneous CO₂ monitoring," he said, adding: "Remember, hypoxemia is a late finding of opioid-related respiratory depression. You’re going to see a slight elevation in carbon dioxide first."

Adverse effects are most common in those at the extremes of age, in those with underlying systemic diseases, and in those receiving other agents that are central nervous system depressants.

Of course, the best way to limit side effects is to use adjunctive agents, Dr. Tobias said.

"Maximize the use of nonsteroidals and acetaminophen, and you’re going to use a lot less opioid," he said.

Another important approach to reducing opioid use is the perioperative use of regional anesthesia.

"If you’re working in the hospital taking care of kids after major surgical procedures, I think if you partner with the anesthesia team there’s a lot you can do perioperatively to almost eliminate the need for intravenous opioids," he said.

For a femur fracture patient, for example, a catheter can be placed near the femoral nerve to provide analgesia, or the lateral femoral cutaneous nerve can be blocked. Ultrasound has "really opened the door for regional anesthesia."

Home infusion devices are also available.

"So if you’re having your anterior cruciate ligament repaired, where I work, you’re going to go home with a femoral nerve catheter and a home infusion device that will work for 3 days and really limit your need for parenteral and oral opioids," he said.

Outside of the operating room, regional anesthesia can be used to treat pain that is unresponsive to opioids or if the opioids are causing side effects. Cases involving sickle cell vaso-occlusive crisis, multiple trauma, or burns are scenarios in which regional anesthesia can be particularly useful, he said.

Dr. Tobias reported having no disclosures.