For B.B., there needs to be education about her substance use. Many surgeons

require patients to stop smoking prior to surgery to improve healing (see Chapter 91

Tobacco Use and Dependence for smoking cessation strategies). Given her regular

intake of alcohol, tapering off this prior to surgery is important, because she may

develop alcohol withdrawal after surgery if she continues to consume alcohol. This

complicates postoperative care and prevents use of valuable analgesics such as

acetaminophen due to additive liver toxicity. Because she is getting little to no

benefit from her opioid, it is recommended to discontinue

hydrocodone/acetaminophen via taper over the next two weeks to reduce her

tolerance and improve her postoperative response to opioid analgesics. Some time

needs to be devoted to reducing her anxiety and educating her that she may have an

exaggerated pain response. Increasing the dose of pregabalin may help with this as

part of a multimodal analgesic regimen, and duloxetine could be continued.

CASE 55-1, QUESTION 3: Based on current guidelines, what postoperative pain management approaches

are appropriate for B.B.?

Clinicians should use regional or intraspinal analgesia whenever possible to

reduce the neuronal response to surgery. Surgery in the extremities is most often

managed with regional nerve blocks, using a local anesthetic such as bupivacaine or

ropivacaine. There are both sensory nerves and motor nerves that extend from the

spinal cord. The sensory nerves carry pain, temperature, pressure, and chemical

messages from the area of injury to the spine and brain for processing. Sensory

nerves are small and very sensitive to local anesthetics. Local anesthetics act as

sodium-channel blockers and, depending on how concentrated the local anesthetic is

(0.05% vs. 0.1%), it is possible to achieve a very dense block and completely stop

transmission. Unfortunately, with a really dense block, nerve transmission is retarded

or stopped in the larger motor nerves as well, causing loss of motor function. For

BB, the anesthesia team will consider a nerve block (likely an interscalene nerve

block) either as a one-shot block or a continuous infusion. The one-shot blocks only

last a few hours (Table 55-6). Because shoulder surgery is so painful and recovery

so long, some hospitals send patients home with a continuous infusion of local

anesthetic for pain relief up to 7 days. If they do this for B.B, she will have her arm

in a sling because her arm and hand will be numb and not functional while the nerve

block is running. This form of longer term acute analgesia has been shown to reduce

length of stay as well as provide excellent pain relief.

36 Some surgeons use local

anesthetics for localized joint or tissue infiltration in and around the surgical incision

to offer short-term analgesia. A liposomal bupivacaine may be used as well. This

may offer slightly longer analgesia in the area where administered.

For thoracic and abdominal surgeries, there are several analgesic options to

reduce opioid need. Spinals are one-time injections of either opioid and/or local

anesthetic into the subarachnoid (intrathecal) space. Because this is not a continuous

infusion, the analgesia will wear off according to the half-life of the drug used. Some

anesthesiologists use a small amount of epinephrine to cause local vasoconstriction

and keep the medication from dispersing through the cerebrospinal fluid (CSF).

Common complications with spinal injections include postdural puncture headaches

(i.e., CSF can leak after puncture of the subarachnoid dura) and itching (with

opioids). More serious complications include delayed respiratory depression (with

opioids), hypotension (with local anesthetics), infection, and intraspinal hematomas.

Epidurals offer the convenience of a continuous infusion of opioid and/or local

anesthetic. The medication chosen, concentration, and infusion rate all offer different

options for a given clinical situation. Morphine, hydromorphone, and an agent from

the fentanyl family are the opioids most commonly used. The pKa and lipophilicity

help determine the best agent. Morphine and hydromorphone are more hydrophilic so

it is more difficult for them to pass through membranes (to get into the CSF or

systemic blood) once injected into the epidural space. This is advantageous because

they stay in that space, and infusions can be used for up to 7 days. The fentanylrelated agents are highly lipophilic and easily pass through membranes into the

systemic circulation and CSF. Typically, they are not used for longer than 24 hours

due to this, but are often used for epidurals during labor. All epidural opioids travel

cephalad to the brain via the CSF and may cause central respiratory depression.

Epidural opioids also cause typical class-related adverse effects such as itching and

nausea, and cognitive effects such as sedation or confusion, although these are

centrally mediated.

Some clinicians limit opioid use further by only using local anesthetics in epidural

infusions. The local anesthetic chosen depends on half-life and toxicity. Lidocaine is

used for local infiltration because it has a short onset of action. However, it also has

a short half-life so usually bupivacaine or ropivacaine is used for blocks (Table 55-

6). Usually these are infused via an epidural catheter. The catheter tip is placed

where the densest block is needed. The greater the concentration, the denser the

block. Increasing the infusion rate causes the local anesthetic to spread over more

spinal nerve roots. This causes a greater clinical area of anesthesia. For example, if a

patient has a total colectomy and the incision area is still painful on the most

cephalad part, the infusion rate can be increased so some of the higher nerve roots

are covered. Local anesthetics must be monitored not only for pain coverage but also

for toxicity. They most commonly cause hypotension, because sympathetic nerves are

small. The more cephalad the epidural catheter tip is placed, the more likely that the

sympathetic nerves serving the lungs, diaphragm, and heart will be affected. Local

anesthetic systemic toxicity (LAST) can be life threatening, causing seizures and

cardiac dysrhythmias. The treatment of LAST involves rapid administration of

intralipid, which will bind the local anesthetic.

37

Table 55-6

Local Anesthetics

Agent Onset (minute) pKa Duration (hour)

Maximum dose

(mg/kg)

Lidocaine 10–20 7.8 1–2 4.5

Mepivacaine 10–20 7.7 1.5–3 5

Prilocaine (topical) <60 8.0 1–2 6

Ropivacaine 15–30 8.1 4–8 2.5

Bupivacaine 15–30 8.1 4–8 2.5

Chloroprocaine 10–15 9.1 0.5–1 9

Procaine 2–5 8.9 0.75–1 7

Tetracaine 3–5 8.4 3 1.5

Cocaine (topical) 1 8.7 0.5 0.5

p. 1177

p. 1178

Multimodal Pain Management

CASE 55-2

QUESTION 1: D.K. is a 35-year-old male admitted for elective surgery of an inguinal hernia that has been

present for 8 months. The hernia presented as a protruding bulge, 4 cm in diameter, in the lower right abdominal

quadrant that was noticeable with standing and retracted inward when lying down. There was no pain initially

with the hernia or incarceration of internal structures so conservative management with observation was

appropriate until approximately 4 weeks ago when the patient noted the size of the hernia was increasing and

experienced pain shooting down the right leg when walking. An ultrasound of the right groin confirmed an

inguinal hernia sac, 6 cm in diameter, with no incarceration. The patient was scheduled for an open repair using

the Lichtenstein technique with polypropylene mesh reinforcement of the anterior abdominal wall. Prior to

admission for the surgery, the patient’s medical history included:

Medical conditions:

Morbid obesity (height 1.8 m, weight 171 kg, BMI 51.5 kg/m

2

)

Type 2 diabetes, noninsulin dependent

Sleep apnea, uses CPAP at home

Chronic kidney disease, baseline serum creatinine 1.4 mg/dL

Hypertension

Medications:

Glimepiride 8 mg orally once daily

Lisinopril 20 mg orally once daily

Ibuprofen 600 mg orally once or twice daily for groin pain

In the postoperative anesthesia care unit (PACU), morphine 2 to 4 mg intravenous every 5 minutes is

ordered for severe pain. D.K. received 8 mg of intravenous morphine over 30 minutes then became very

drowsy but still reporting severe pain. The nurse is concerned about the level of sedation and does not want to

give additional morphine. Is morphine an appropriate opioid for postoperative pain control in D.K.?

After surgery is completed in the operating room, patients are transferred to the

PACU for stabilization of respiratory function and pain. Most patients emerging from

general anesthesia are still quite sedated when they are transferred to the PACU.

When the anesthetic agents begin to wear off, it is very important to achieve rapid

control of severe pain so frequent administration of small intravenous opioid doses is

common practice in this setting. Currently, there is not a universally accepted

standard for titration of intravenous opioids in the PACU. Some institutions will

allow use of both intravenous fentanyl to gain fast pain control and morphine for a

longer duration of action. Hydromorphone is an acceptable alternative to morphine

for patients with renal insufficiency or intolerable side effects to morphine.

Morphine is considered the standard for intravenous opioid administration. The

hydrophilic (i.e., water soluble) property of morphine delays penetration across the

blood–brain barrier so the relative time to onset is approximately 6 minutes after an

intravenous dose. The concentration peak effect (i.e., equilibration time between the

plasma and brain) after an intravenous morphine dose is 20 minutes.

38 Major

morphine metabolites include morphine-3-glucuronide (M3G) and morphine-6-

glucuronide (M6G).

39 The M3G metabolite is inactive but M6G crosses the blood–

brain barrier and has potent analgesic activity. Therefore, the analgesic and

ventilatory depressant effects of morphine and M6G may not be evident with initial

high plasma morphine concentrations.

40 Adverse events may occur 40 to 60 minutes

after the last intravenous morphine dose.

40 Patients with renal insufficiency will have

M6G metabolite accumulation and be at increased risk for respiratory depression so

morphine use is not recommended in this population.

41

Hydromorphone is commonly used in patients who cannot tolerate morphine or

have a history of renal insufficiency.

42,43 Hydromorphone is a hydrogenated ketone

analogue of morphine with slightly higher lipid solubility. The concentration peak

effect after intravenous hydromorphone administration is between 8 and 20

minutes.

44,45 Hydromorphone has a similar metabolic pathway to morphine producing

hydromorphone-3-glucuronide (H3G) and hydromorphone-6-glucuronide (H6G).

However, hydromorphone metabolites are devoid of analgesic activity but H3G has

been showed to accumulate in animal models leading to dose-dependent myoclonus.

45

Fentanyl is a synthetic phenylpiperidine compound with high lipid solubility

resulting in rapid transfer across the blood–brain barrier. The concentration peak

effect after intravenous fentanyl administration can be seen within 4 to 6 minutes.

46

Fentanyl is a good option for rapid pain control but may accumulate in adipose tissue

with multiple doses; therefore, it is not the best choice for obese patients.

46

For management of D.K.’s pain in the PACU, the morphine order should be

changed to intravenous hydromorphone at 0.2 to 0.4 mg every 10 minutes for severe

pain. Hydromorphone does not have appreciable metabolite accumulation with renal

insufficiency and does not distribute into adipose tissue. After D.K.’s pain is

stabilized in the PACU, the interval will need to be longer between doses due to the

declining acute pain trajectory and addition of other multimodal medications that will

decrease the opioid requirements (Table 55-7). In addition to pain management, it is

very important to anticipate postoperative nausea and vomiting (PONV) caused by

anesthetic agents and opioids. Antiemetics are commonly used for prevention of

severe PONV (refer to Chapter 22 for management of PONV).

CASE 55-2, QUESTION 2: Is D.K. an appropriate candidate for intravenous patient-controlled analgesia

(PCA)?

For postoperative pain management after discharge from the PACU, the oral route

is preferred over intravenous administration unless the patient is unable to use this

route or has severe uncontrolled pain.

30 The use of PCA provides a precise and

convenient method for intravenous opioid administration that allows the patient to

activate the dose for acute pain management. The intravenous PCA route is preferred

over nurse-administered intravenous doses because the patient does not have to

notify the nurse when more medication is needed, wait until it is given, and then

further wait for the peak effect to occur for pain relief. Self-administration of smaller

and more frequent intravenous opioid doses reduces the variation between the peak

and trough effect of the dosing interval thus better maintenance of the plasma opioid

concentration.

47 Evidence-based guidelines on the management of postoperative pain

strongly recommend use of PCA for the intravenous route in surgical patients because

of ileus, aspiration risk, or inability to take medications orally or enterally.

30

p. 1178

p. 1179

Table 55-7

Postoperative Transition of Opioid Doses for Naive Patients >50 Kg

30,42,48

Postanesthesia Care Unit

Fentanyl intravenous 25–50 mcg every 5 minutes as needed

Morphine intravenous 2–4 mg every 5 minutes as needed

Hydromorphone intravenous 0.2–0.4 mg every 5 minutes as needed

Medical/Surgical Hospital Floor

Patient-controlled Analgesia (PCA) Starting Dose

Morphine intravenous 1 mg every 10 minutes

Hydromorphone intravenous 0.2 mg every 10 minutes

Fentanyl intravenous 25 mcg every 10 minutes

Nurse-Administered Opioid Dose for Patients Unable to Use PCA

Morphine intravenous 2–4 mg every 2 hours as needed

Hydromorphone intravenous 0.25–0.5 mg every 2 hours as needed

Discharge Planning

Hydromorphone 2–4 mg orally every 4 hours as needed

Oxycodone 5–10 mg orally every 4 hours as needed (can be combined with acetaminophen 325 mg)

Hydrocodone 5 mg with acetaminophen 325 mg—1 to 2 tablets orally every 4 hours as needed

Important

Long-acting opioid formulations are not recommended for acute postoperative pain management unless the

patient was taking opioid therapy for chronic pain prior to surgery.

Patients who are appropriate for PCA must be able to cognitively understand how

to use a dose button for opioid self-administration and require intravenous opioid for

many hours.

30 The PCA dose button is connected to an infusion pump that will allow

the administration of an opioid dose when the button is pushed (i.e., demand). To

prevent over dosage by continual demand, all PCA devices use a lockout interval

which is the length of time after a successful patient demand during which the device

will not administer another dose even if the patient pushes the button.

47 Most patients

who start intravenous PCA are opioid-naïve meaning that their opioid use the week

prior to surgery was less than 60 mg of oral morphine or its equivalent.

42,48 For this

reason, the starting dose for intravenous PCA is standardized for opioid-naïve

patients (Table 55-7).

Use of a continuous opioid infusion for postoperative pain management is

generally reserved for patients who are opioid-tolerant and were taking opioid

medication around-the-clock prior to surgery. The role of the continuous infusion is

to provide a steady baseline of opioid medication that mimics the dose taken prior to

surgery. Equianalgesic dose calculations are used to determine the dose difference

between two opioids to provide the same degree of pain relief. When switching

between two opioids, it is recommended to decrease the new calculated dose by

25% to 50% to account for incomplete cross tolerance that may occur.

42 Use of

intravenous PCA along with a continuous infusion in opioid-tolerant patients can help

fine-tune pain control (refer to Case 55-8 for examples of equianalgesic dose

calculations).

Respiratory depression remains the most serious adverse event related to opioid

therapy often due to excessive amounts or frequent use of opioid medication beyond

what is needed to achieve pain control.

42,47 There are many factors that increase the

risk of opioid-induced respiratory depression with intravenous PCA related to

comorbid medical conditions. Patients with advanced age >65 years, renal

insufficiency, history of sleep apnea, or morbid obesity are at higher risk for

developing opioid-induced respiratory depression. To prevent respiratory

depression in high-risk patients, the lowest possible starting dose of an opioid should

be initiated, and use of a continuous infusion should be avoided. For all patients,

avoid administration of more than one drug with sedating properties at the same time

with opioids.

30 Medications including antihistamines, benzodiazepines, gabapentin,

pregabalin, and skeletal muscle relaxants should be scheduled approximately 2 hours

apart to prevent accumulation of sedating side effects.

For hospitalized patients who experience excessive sedation and cannot be

aroused with sternal stimulation, or have a significant decline in breathing, naloxone

administration may be needed to reverse the opioid CNS effects. Naloxone is a

nonselective competitive opioid antagonist of all pharmacologic effects on mu, delta,

and kappa receptors. After oral administration, naloxone is extensively metabolized

in the liver (i.e., >95% first pass effect) and not effective so intravenous,

intramuscular, or subcutaneous administration at a dose of 0.4 mg is required for

reversal of life-threatening respiratory depression. The extent and duration of

naloxone reversal of opioid-induced respiratory effects is highly variable and is

related to many factors, including the specific opioid used, the opioid dose,

administration mode, concurrent medication, underlying disease, and pain. Therefore,

naloxone administration may need to be repeated every 2 to 3 minutes or given as a

continuous infusion until full recovery of respiratory function.

49

In this case, PCA therapy would be appropriate for D.K. based on the invasive

surgery and anticipated severe postoperative pain. Hydromorphone 0.2 mg

intravenously with a lockout interval of 10 minutes is recommended because D.K. is

at high risk for respiratory depression being opioid-naïve, morbidly obese, and

having chronic renal insufficiency. Because D.K. is experiencing sedation due to

morphine administration in the PACU, the PCA dose should be started after he is

more alert. Other analgesic medications that are not sedating should be used to

provide synergistic pain management and can be used throughout the postoperative

period.

As soon as DK can tolerate oral medication, the intravenous PCA dose should be

discontinued and a short-acting oral opioid such as oxycodone or hydromorphone

administered as needed with frequent reassessment of pain. Because DK is opioidnaïve, the lowest starting dose should be prescribed so oxycodone 5 to 10 mg every

4 hours as needed or hydromorphone 2 to 4 mg every 4 hours as needed would be

options in this case. Oral short-acting morphine is not recommended due to concern

for metabolite accumulation with renal insufficiency. Long-acting oral formulations

(i.e., sustained or extended release) should be avoided in opioid-naive patients who

cannot tolerate around-the-clock opioid administration for a prolonged period of

time. Recent guidelines for postoperative pain do not recommend long-acting oral

opioids due to the need for pain titration with short-acting opioid, and studies have

not shown that pain control with a long-acting opioid is superior to short-acting

opioid administration immediately after surgery.

30

When DK is ready for discharge, a prescription for a limited supply of short-acting

opioid should be written to cover the duration of 3 days.

50 This is particularly

important because prescription opioid abuse is a national crisis and prescription

opioid overdose is now the leading cause of unintentional deaths in the United

p. 1179

p. 1180

States.

50